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Mycotoxin References

Fungal Glossary Mycotoxin References as provided by Texas Tech University Health Sciences Center, Department of Microbiology and Immunology

1Atlas of Clinical Fungi. 2nd edition. G.S. de Hoog, J.Guarro, J.Gene & M.J. Figuerras. - Centraalbureau voor Schimmelcultures/Universitat Rovira I Virgili Reus, Spain. - 2000. 
2Guide to Clinically Significant Fungi. Deanna A.Sutton, Annette W.Fothergill, Michael G.Rinaldi. - Williams & Wilkins A Wavely Company. - 1998. 
3Introduction to food and airborne fungi. Sixth Edition. Robert A. Samson, Ellen. S Hoekstra, Jens C. Frisvad, Ole Filtenborg.Centraalbureau Voor Schimmelcultures Utrecht. An Institute of the Royal Netherlands Academy of Arts and Sciences. Ponsen & Looyen. Wagemimgen, The Netherlands. - 2000. 
4Compendium of Soil Fungi. K.H. Domsch, W. Gams, Traute-Heidi Anderson. Reprint der Ausg. Von 1980 - 1993. 
10Cytotoxins, mycotoxins and drugs from a new deuteromycete, Acremonium neo-caledoniae, from the southwestern lagoon of New Caledonia. Laurent D, Guella G, Roquebert MF, Farinole F, Mancini I, Pietra F. Planta Med. 2000 Feb;66(1):63-6.A new cytotoxic trichothecene sesquiterpene, verrol 4-acetate, was isolated, along with known macrocyclic trichothene mycotoxins and medicinal styrylpyrones, from cultures of a new deuteromycete Acremonium neo-caledoniae Roquebert et Dupont n. sp., taken from drifting wood in the southwestern lagoon of New Caledonia.
13Morphological and rheological properties of culture broth of Cephalosporium acremonium M25 Jung Soo Lim, Jin Hee Kim, Chongyoup Kim and Seung Wook Kim* . Korea Australia Rheology Journal. 2002,March,Vol 14, No 1., pp 11-16.Cephalosporium acremonium is a filamentous microorganism producing cephalosporin C. The mor phological differentiation ofC. acremonium in submerged culture is closely related with the rheological properties of culture broth and production of cephalosporin C. In this study, the rheological and morphological properties of culture broth of C. acremonium were investigated. In the seed broths of shake-flask and fermenter culture, the Herschel-Berkley equation was in excellent agreement with experimental results in the whole range of shear rate. In the seed broths of shake-flask culture, morphological differentiation into arthrospores affected to changes of apparent viscosity. But results in the fermenter culture, morphological factors such as mean hyphal thickness and the number of tips gave more effect on changes of apparent viscosity than differentiation into arthrospores. Overall, it suggested that the morphological parameters measured by image analysis can be used as a good parameter to indicate the rheological properties of culture broth of C. acremonium M25.
14Evaluation of acrodontiolamide, a chlorinated compound produced by Acrodontium salmoneum de Hoog for cytotoxicity and antimicrobial activity. Steiman R, Benoit-Guyod JL, Guiraud P, Seigle-Murandi F. Pharmazie. 1995 Oct;50(10):693-5.A new antifungal compound has been isolated from the culture medium of Acrodontium salmoneum de Hoog. Its structure was previously elucidated and was named acrodontiolamide. However, this compound is not characteristically produced by the genus Acrodontium, it is rather a feature of one isolate of A. Salmoneum coming from the soil of the grotto of La Pierre Saint Martin (France). Production, purification, cytotoxicity and antimicrobial activities of acrodontiolamide are described. Concerning microorganisms, inhibitory activity seems to be specifically restricted to phytopathogenic and entomapathogenic fungi. Acrodontiolamide is not cytotoxic to either normal human cultured cells or tumor cells.
24Production of mycotoxins on artificially and naturally infested building materials. Nielsen KF, Gravesen S, Nielsen PA, Andersen B, Thrane U, Frisvad JC. Mycopathologia. 1999;145(1):43-56.In this study, the ability to produce mycotoxins during growth on artificially infested building materials was investigated for Penicillium chrysogenum, Pen. polonicum, Pen. brevicompactum, Chaetomium spp., Aspergillus ustus, Asp. niger, Ulocladium spp., Alternaria spp., and Paecilomyces spp., all isolated from water-damaged building materials. Spores from the different isolates of the above mentioned species were inoculated on gypsum board with and without wallpaper and on chipboard with and without wallpaper. Fungal material was scraped off the materials, extracted, and analyzed using high performance liquid chromatography-diode array detection and thin layer chromatography. All six isolates of C. globosum produced the toxic chaetoglobosins A and C, at levels of up to 50 and 7 microg/cm2 respectively. The quantities of secondary metabolites produced by Penicillia were generally low, and no toxin production was detected from any of the five isolates of Pen. chrysogenum. Both isolates of Pen. polonicum produced 3-methoxy-viridicatin, verrucosidin, and verrucofortine. Two of five isolates of Pen. brevicompactum produced mycophenolic acid. From five out of six isolates of Alternaria spp., altenariol and alternariol monomethyl ether were detected. From Ulocladium spp., Paecilomyces spp., and Asp. ustus no known mycotoxins were detected, although the latter two are known mycotoxin producers. Asp. niger produced several naphtho-gamma-pyrones and tetra-cyclic compounds. All investigated species, especially Asp. ustus and Asp. niger produced many unknown secondary metabolites on the building materials. Analyses of wallpaper and glass-fibre wallpaper naturally infested with Asp. versicolor revealed sterigmatocystin and 5-methoxysterigmatocystin. Analyses of naturally infested wallpaper showed that C. globosum produced the chaetoglobosins A and C, and Pen. chrysogenum produced the antibiotic meleagrin.
25Analysis of agricultural commodities and foods for Alternaria mycotoxins. Scott PM. J AOAC Int. 2001 Nov-Dec;84(6):1809-17.Fungi of the genus Alternaria are parasitic on plants and other organic materials. A. alternata is a frequently occurring species of particular interest because it produces a number of mycotoxins, including alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT), altertoxins I, II, and III (ATX-I, -II, and -III), and L-tenuazonic acid (TeA). Cleanup procedures of analytical methods for foods and foodstuffs include solvent partition, generally used for TeA, and solid-phase extraction columns for AOH, AME, and ATX-I. These Alternaria mycotoxins have been determined by TLC, GC, and more usually LC, mainly with ultraviolet detection, although fluorescence and electrochemical detection have also been used for Alternaria toxins other than TeA. A Zn2+ salt is usually added to the LC mobile phase for TeA. Recently, atmospheric pressure chemical ionization and electrospray LC/MS and LC-MS/MS have been applied to the determination and confirmation of AOH and AME in apple juice and other fruit beverages at sub ng/mL levels. Natural occurrences of AOH, AME, and in some cases other Alternaria toxins have been reported in various fruits, including tomatoes, olives, mandarins, melons, peppers, apples, and raspberries. They have been found also in processed fruit products such as apple juice, other fruit beverages and tomato products, wheat and other grains, sunflower seeds, oilseed rape meal, and pecans.
26Brefeldin A, a cytotoxin produced by Paecilomyces sp. and Aspergillus clavatus isolated from Taxus mairei and Torreya grandis. Wang J, Huang Y, Fang M, Zhang Y, Zheng Z, Zhao Y, Su W. FEMS Immunol Med Microbiol. 2002 Sep 6;34(1):51.Paecilomyces sp. and Aspergillus clavatus, which were isolated from Taxus mairei and Torreya grandis from southeast China, produced toxic metabolites when grown in liquid culture. Nuclear magnetic resonance techniques, infrared spectrometry, electrospray ionization mass spectroscopy and X-ray analysis identified brefeldin A, a bioactive metabolite produced by a number of fungal species belonging to the genera Alternaria, Ascochyta, Penicillium, Curvularia, Cercospora and Phyllosticta. This is the first report of the isolation of the cytotoxin from Paecilomyces sp. and A. clavatus. The relevance of brefeldin A to the association between these fungi and their host plants is discussed.

New sources of cytochalasins A and B from dematiaceous hyphomycetes. Zohri AA, Saber SM. Lett Appl Microbiol. 1994 Jul;19(1):37-9.

One hundred isolates of 27 species belonging to 13 genera of dematiaceous hyphomycetes were screened for production of cytochalasins A and B. Most of these isolates (94) were obtained from Assiut University Culture Collection, Botany Department, Faculty of Science, Assiut University, Egypt; three isolates from CBS, The Netherlands; two isolates from DSM, Germany; and one isolate from IMI, UK. The results revealed that 10 isolates of six species representing five genera of fungi produced cytochalasins A and/or B. These species are Alternaria chlamydospora, Cochliobolus spicifer, Diplococcum spicatum, Phoma herbarum, Phoma multipora and Setosphaeria rostrata. This is the first report for the production of cytochalasins A and/or B by these species of dematiaceous hyphomycetes.
28Comparison of the phytotoxic activity of the phytotoxin destruxin B and four natural analogs. Pedras MS, Biesenthal CJ, Zaharia IL. Plant Science. 2000 Jul 28;156(2):185-192.A quantitative bioassay utilizing staining of plant cell suspension cultures of Sinapis alba was employed to establish a structure-phytotoxic activity correlation among destruxin B, homodestruxin B, and desmethyldestruxin B, toxins produced by Alternaria brassicae (Berk.) Sacc., the causative agent of Alternaria blackspot of brassicas. In addition, the phytotoxicity of destruxin B, homodestruxin B, and their respective metabolites hydroxydestruxin B and hydroxyhomodestruxin B were tested on resistant and susceptible plant species utilizing in planta leaf assays and leaf uptake of toxin solutions. Overall, the results obtained from punctured leaf and cell staining assays indicated that homodestruxin B (EC(50) 3x10(-4) M) was the most toxic of the five compounds, followed by destruxin B (EC(50) 5x10(-4) M), and desmethyldestruxin B (EC(50)&z.Gt;5x10(-4) M). On the other hand, the hydroxylated destruxins (hydroxydestruxin B EC(50)&z.Gt;5x10(-4) M) were significantly less phytotoxic than the parent toxins.

Radioimmunoassay of the phytotoxic compound zinniol. Montillet JL, Rossignol M, Auriol P. J Immunoassay. 1987;8(1):11-27.

The phytotoxic compound zinniol, produced by phytopathogenic fungi such as Alternaria spp. and Phoma macdonaldii was conjugated to bovine serum albumine by the mixed anhydride method. Antiserum against zinniol was obtained by injection at multiple intradermal sites of rabbits. Sensitivity of the R.I.A. was 0.14 ng/tube, the within and between-assay coefficient of variation were less than 10 and 14% respectively. Negligible binding occurred when analogs of zinniol were tested for cross reactivity. The excellent accuracy of this R.I.A., applied to ethanolic extracts of plants, might allow to determine the production of toxin by the parasite during the infection process.
40Apiosporamide, a new antifungal agent from the coprophilous fungus Apiospora montagnei. Alfatafta AA, Gloer JB, Scott JA, Malloch D. J Nat Prod. 1994 Dec;57(12):1696-702.Bioassay-guided fractionation of an EtOAc extract from the mycelium of the coprophilous fungus Apiospora montagnei has furnished a new antifungal metabolite, named apiosporamide [1], and the known dihydroisocoumarin cis-(3R,4R)-4-hydroxymellein [4]. The structure of 1 was assigned on the basis of HMBC, HMQC, NOESY, and hrms data. Elucidation of the structure was complicated by the fact that several nmr signals appeared only under certain conditions.
41Secondary metabolites with nematicidal and antimicrobial activity from nematophagous fungi and Ascomycetes. Anke N., Stadler M., Mayer A., Sterner O. Canadian Journal of Botany; 73 (Suppl. 1 Sect. E-H). 1995. S932-S939.Screening Of nematode-trapping fungi for antimicrobial and nematicidal activities gave three new antimicrobial metabolites from cultures of five Arthrobotrys strains. The compounds exhibited no nematicidal activities towards Caenorhabditis elegans and Meloidogyne incognita. From trap-forming submerged cultures of Arthrobotrys conoides, linoleic acid was isolated as a nematicidal principle. Its production increased with the number of traps formed in both Arthrobotrys oligospora and Arthrobotrys conoides. Nematoctonus robustus and Nematoctonus concurrens produced pleurotin, dihydropleurotinic acid, and leucopleurotin, metabolites previously isolated from cultures of Hohenbuehelia species, suggesting that the same biosynthetic pathways function in both the teleomorph and anamorph. Several strains of Ascomycetes had nematicidal activities; linoleic acid was responsible for the activity in cultures of a Chlorosplenium species, 14-epicochlioquinone B in cultures of Neobulgar
42Structures and absolute configurations of antibiotics of the oligosporon group from the nematode-trapping fungus Arthrobotrys oligospora. Anderson MG, Jarman TB, Rickards RW. J Antibiot (Tokyo). 1995 May;48(5):391-8.Spectroscopic data define the structures of three new antibiotics, 4',5'-dihydro-oligosporon (4), hydroxyoligosporon (5) and 10',11'-epoxyoligosporon (6) from the nematode-trapping fungus Arthrobotrys oligospora, and confirm the structures of the recently reported antibiotics oligosporon (1) and oligosporol B (3). The absolute configuration of the substituted 7-oxabicyclo[4.1.0]hept-3-ene nucleus of these metabolites is determined by circular dichroic spectroscopy. Oligosporon (1) and its dihydro-derivative (4) represent the second and most complex structural type of nematocidal metabolite to be characterised from cultures of nematophagous fungi.
46Aflatoxin-like compounds produced by dermatophytes. Kaliciński J, Prochacki H, Engelhardt-Zasada C. Mycopathologia. 1975 Feb 28;55(1):23-4.Using the method of thin-layer chromatography there were investigated the chloroform extracts of 30 dermatophyte mycelia. It was found the presence of aflatoxin-like compounds in six mycelium extracts only, which chromatograms showed the equal Rf and the colour of the strains to the strains to the standard aflatoxin extract of bruished peanuts grain Rossetti. Those six mycelia were: Epidermophyton floccosum, Nannizzia fulva, N. persicolor, Arthroderma gloriae, Trichophyton concentricum and T. Gallinae.
50 Ascosteroside, a new antifungal agent from Ascotricha amphitricha. II. Isolation and structure elucidation. Leet JE, Huang S, Klohr SE, McBrien KD. J Antibiot (Tokyo). 1996 Jun;49(6):553-9.The novel antifungal agent ascosteroside (1) was isolated from cultured broth of Ascotricha amphitricha (ATCC 74237). The structure based on spectroscopic data was determined to be an alpha-linked glycoside of a lanostane-type triterpenoid.
51Ascosteroside, a new antifungal agent from Ascotricha amphitricha. I. Taxonomy, fermentation and biological activities. Gorman JA, Chang LP, Clark J, Gustavson DR, Lam KS, Mamber SW, Pirnik D, Ricca C, Fernandes PB, O'Sullivan J. J Antibiot (Tokyo). 1996 Jun;49(6):547-52.Ascosteroside, a novel antifungal compound, was isolated from the culture broth of Ascotricha amphitricha. This compound is an alpha-linked glycoside of a lanostane type triterpenoid. It is active against yeasts such as Candida albicans and Saccharomyces cerevisiae and against filamentous fungi but shows no activity against bacteria. It is not toxic to mammalian cells at concentrations up to 150 microM. In a mouse model, the compound afforded protection comparable to that of ketoconazole.
53An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei. Minagawa N, Yabu Y, Kita K, Nagai K, Ohta N, Meguro K, Sakajo S, Yoshimoto A. Mol Biochem Parasitol. 1997 Feb;84(2):271-80.Ascofuranone, a prenylphenol antibiotic isolated from a phytopathogenic fungus, Ascochyta visiae, strongly inhibited both glucose-dependent cellular respiration and glycerol-3-phosphate-dependent mitochondrial O2 consumption of long slender bloodstream forms of Trypanosoma brucei brucei. This inhibition was suggested to be due to inhibition of the mitochondrial electron-transport system, composed of glycerol-3-phosphate dehydrogenase (EC and plant-like alternative oxidase. Ascofuranone noncompetitively inhibited the reduced coenzyme Q1-dependent O2 uptake of the mitochondria with respect to ubiquinol (Ki = 2.38 nM). Therefore, the susceptible site is deduced to be the ubiquinone redox machinery which links the two enzyme activities. Further, ascofuranone in combination with glycerol completely blocked energy production, and potently inhibited the in vitro growth of the parasite. Our findings suggest that ascofuranone might be a promising candidate for the chemotherapeutic agents of African trypanosomiasis.
54Ascosalipyrrolidinone A, an antimicrobial alkaloid, from the obligate marine fungus Ascochyta salicorniae. Osterhage C, Kaminsky R, König GM, Wright AD. J Org Chem. 2000 Oct 6;65(20):6412-7.From the green alga Ulva sp., the endophytic and obligate marine fungus Ascochyta salicorniae was isolated. A. salicorniae was mass cultivated and found to produce the unprecedented and structurally unusual tetramic acid containing metabolites ascosalipyrrolidinones A (1) and B (2). Additionally, the new natural product ascosalipyrone (3) and the known metabolites 4 and 5 were obtained. Ascosalipyrrolidinone A (1) has antiplasmodial activity toward Plasmodium falciparum strains K1 and NF 54, as well as showing antimicrobial activity and inhibiting tyrosine kinase p56lck.
55Determination of Ascochyta caulina phytotoxins by high-performance anion exchange chromatography and pulsed amperometric detection. Evidente A, Andolfi A, Vurro M, Zonno MC. Phytochem Anal. 2001 Nov-Dec;12(6):383-7.A simple and sensitive method has been developed for the rapid qualitative and quantitative analysis of the phytotoxins produced by Ascochyta caulina, a potential mycoherbicide for the biocontrol of Chenopodium album. Considering that the two main toxins produced by this fungus, namely ascaulitoxin and trans-4-amino-D-proline, and the third toxin, identified as 2,4,7-triamino-5-hydroxyoctandioic acid, have an amino acid nature, high-performance anion exchange chromatography with pulsed amperometric detection was the best method for their detection. The method was used to measure the toxin content in the culture filtrates of different strains of A. caulina. The developed method could be employed as a tool to select more virulent strains by determining the higher toxin producers, if in vitro toxin accumulation was related to pathogen virulence. The chemical characterisation of the third toxin purified from A. caulina culture filtrates is also reported.
56Trans-4-aminoproline, a phytotoxic metabolite with herbicidal activity produced by Ascochyta caulina. Evidente A, Andolfi A, Vurro M, Zonno MC, Motta A. Phytochemistry. 2000 Jan;53(2):231-7.A phytotoxic metabolite, characterized through NMR techniques and synthetic methods as trans-4-aminoproline, was isolated from the culture filtrates of Ascochyta caulina, a promising mycoherbicide for biological control of Chenopodium album. The metabolite, which shows interesting phytotoxic properties, together with ascaulitoxin (recently characterized as N.2-beta-D-glucoside of the unusual bis-amino acid 2,4,7-triamino-5-hydroxyoctandioc acid) and another unidentified compound, compose an active fraction of A. caulina culture filtrates with promising herbicidal properties. When assayed on leaves of host and non host dicots, including wild and cultivated plants, the trans-4-aminoproline showed a wide range of toxicity, with leaves of C. album being the most sensitive. Other interesting aspects were its inefficacy on several monocots, both cultivated and wild, and its lack of antifungal, antibiotic and zootoxic activities. This is the first report on trans-4-aminoproline as naturally occurring compound and phytotoxic metabolite produced by A. caulina.
57Toxic metabolites from phytopathogenic Ascochyta species. Evidente A, Capasso R, Motta A, Andolfi A, Vurro M, Zonno MC, Bottalico A. Boll Chim Farm. 1996 Oct;135(9):552-5.We review some chemical and biological aspects of toxic metabolites produced in vitro by phytopathogenic Ascochyta species, fungi having agrarian and toxicological importance. In particular, here the isolation of some known and new cytochalasins from A. heteromorpha and A. lathyri, four new nonenolides from A. pinodes and a new trisubstituted derivative of salycilic aldehyde from A. pisi are described. Furthermore, the identification of medicarpin, phytoalexin found in the chickpea seeds naturally infected by A. rabiei is also reported.
58Structure-activity relationship studies of putaminoxins and pinolidoxins: phytotoxic nonenolides produced by phytopathogenic Phoma and Ascochyta species. Evidente A, Capasso R, Andolfi A, Vurro M, Zonno MC. Nat Toxins. 1998;6(5):183-8.Putaminoxin and pinolidoxin, two structurally related nonenolides, isolated respectively from organic extracts of Phoma putaminum and Aschochyta pinodes cultures, together with some of their natural analogs and synthetic derivatives, were used in a structure-activity relationship study. Their phytotoxic, antifungal and zootoxic activities were assayed with the aim to find compounds with potential herbicidal properties. The strongest phytotoxic compounds proved to be putaminoxin and pinolidoxin, whose activity appeared to be correlated to the integrity of the nonenolide ring and to the presence of both the hydroxy groups and the unmodified propyl side chain. None of the assayed nonenolides showed antifungal activity, whereas pinolidoxin analogs and derivatives showed high to weak zootoxicity.
59Production of 3-nitropropionic acid by Arthrinium species. Wei D-L., Chang S-C., Lin S-C., Doong M-L., Jong S-C. Current Microbiology; 28 (1). 1994. 1-53-Nitropropionic acid (NPA) is a known toxic metabolite produced by many species of Astragalus of the Leguminosae family. In 1992, Liu et al. reported that some species of Arthrinium were the etiological fungi of moldy sugarcane poisoning (MSP) occurring in China. The toxic metabolite NPA produced by Arthrinium was the main causative agent. Ten percent (88/884) of the MSP patients died, and many were left with lifelong disabilities. In this study, an accurate, sensitive, and rapid method for quantifying NPA produced by Arthrinium species in sugarcane juice was developed. The method includes extraction, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC). Fourteen strains of Arthrinium obtained from the American Type Culture Collection (ATCC) were examined for NPA-producing ability. Eight strains (57.1%), including three of A. sacchari, two of A. phaeospermum, and one each of A. terminalis, A. aureum, and A. sereaensis, were positive for N
60Studies on the epidemiology and etiology of moldy sugarcane poisoning in China. Xingjie L., Xueyun L., Wenjuan H. Biomed Environ Sci; 5 (2). 1992. 161-177.Moldy sugarcane poisoning, an acute fatal food poisoning of unknown etiology, has occurred in 13 provinces in China. The epidemiological characteristics and clinical features were described. Evidence from laboratory studies indicates that 3-nitropropionic acid produced by the fungus Arthrinium Spp. is the etiological factor of this food poisoning
61Moldy sugarcane poisoning--a case report with a brief review. Ming L. J Toxicol Clin Toxicol. 1995;33(4):363-7.A five-year-old girl developed an acute encephalopathy after eating a piece of moldy sugarcane. Delayed symptomatic dystonia was the main effect; cranial CT scans revealed bilateral lenticular lucencies. This case is typical of moldy sugarcane poisoning cases previously reported only in China. 3-Nitropropionic acid produced by Arthrinium sp is the most likely etiologic agent.
62Delayed dystonia with striatal CT lucencies induced by a mycotoxin (3-nitropropionic acid). Full Author Name: He, F; Zhang, S; Qian, F; Zhang, C. He F, Zhang S, Qian F, Zhang C. Neurology. 1995 Dec;45(12):2178-83.We describe a clinical syndrome of delayed dystonia in children subsequent to initial gastrointestinal symptoms and acute noninflammatory encephalopathy. The syndrome was caused by the ingestion of mildewed sugarcane containing the Arthrinium-produced mycotoxin, 3-nitropropionic acid (3-NPA). In the severely affected patients, intoxication usually was heralded by coma, with dystonia appearing 7 to 40 days after recovery from the coma. The dystonia was manifested as choreoathetosis, torsion spasms, or painful paroxysmal spasms of the extremities and was neither progressive nor reversible. CTs of the dystonic patients consistently showed bilateral hypodensities in the lenticular nuclei. The pathogenesis of the selective lenticular lesions induced by 3-NPA is not yet clear.
63Consistent striatal damage in rats induced by 3-nitropropionic acid and cultures of arthrinium fungus. Full Author Name: Fu, Y; He, F; Zhang, S; Jiao, X. Fu Y, He F, Zhang S, Jiao X. Neurotoxicol Teratol. 1995 Jul-Aug;17(4):413-8.Arthrinium fungi were cultivated from the samples of mildewed sugarcane which caused acute encephalopathy and delayed dystonia in children. The Arthrinium cultures (AC) contained 5 mg/ml 3-nitropropionic acid (3-NPA) after being inactivated and concentrated. A neuropathological study was carried out in rats intoxicated with 3-NPA and AC, respectively. This neuropathological evidence supports previous epidemiological and mycological findings which indicate that 3-NPA is the possible pathogen of acute mildewed sugarcane poisoning.
64Phytotoxic sesterterpene, 11-epiterpestacin, from Bipolaris sorokiniana NSDR-011. Nihashi Y, Lim CH, Tanaka C, Miyagawa H, Ueno T. Biosci Biotechnol Biochem. 2002 Mar;66(3):685-8.The structure of siccanol, a phytotoxic sesterterpene of fungal origin, was analyzed after chemical conversion by NMR spectroscopy. Siccanol was found to be an epimer of terpestacin that has been isolated from Arthrinium sp., and was thus renamed 11-epiterpestacin. Its stereochemistry was also identical with that of fusaproliferin, a structurally related mycotoxin from Fusarium proliferatum. Therefore, this sesterterpene may also be referred to as 24-deacetyl fusaproliferin. The phytotoxicity of 11-epiterpestacin was almost equal to that of terpestacin, but significantly higher than that of fusaproliferin.
65 Terpestacin, a new syncytium formation inhibitor from Arthrinium sp. Oka M, Iimura S, Tenmyo O, Sawada Y, Sugawara M, Ohkusa N, Yamamoto H, Kawano K, Hu SL, Fukagawa Y. J Antibiot (Tokyo). 1993 Mar;46(3):367-73.Terpestacin, a new antibiotic which inhibits syncytium formation, was isolated from Arthrinium sp. FA1744 (ATCC 74132). The structure of terpestacin was elucidated as a bicyclic sesterterpene on the basis of spectroscopic data and chemical derivatization.
82Production of patulin and cytochalasin E by Aspergillus clavatus during malting of barley and wheat. Lopez-Diaz TM, Flannigan B. Int J Food Microbiol. 1997 Apr 1;35(2):129-36.Production of patulin and cytochalasin E by four strains of Aspergillus clavatus during small-scale laboratory malting of barley at 16 and 25 degrees C was investigated. Fungal biomass, measured as ergosterol, appeared to be greater at 25 than at 16 degrees C, but marked differences were observed between the degree of colonization by the different strains. Patulin was detected in extracts by HPLC. Net production was greater at 16 degrees C, but amounts were strain dependent. Except for one strain, cytochalasin E was detected only in barley malted at 25 degrees C. In experiments with wheat inoculated with two A. clavatus strains, ergosterol levels in the green malts were generally greater than in corresponding barley malts. Patulin was again detected in all samples, with the equivalent of 22.4 mg/kg being detected in one sample at 16 degrees C, but cytochalasin E was only found at 25 degrees C, the highest level detected being 13.8 mg/kg. In samples of barley spiked with toxin and kilned at 80 degrees C for 24 h, only about one-fifth of the amount of toxin recovered from corresponding unkilned controls was detected. It is indicated that differences in both contaminant strains and temperature in different maltings may account for disparities between symptoms reported for individual outbreaks of mycotoxicosis associated with malting by-products.
83Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan. Lin A, Huang KC, Hwu L, Tzean SS. Toxicon. 1995 Jan;33(1):105-10.A molecular investigation was conducted on the production of type II ribotoxin of the species Aspergillus and related fungi in Taiwan. Species that carried ribotoxin were confirmed by (1) cross-reactivity to anti-alpha-sarcin serum; (2) Southern dot hybridization; (3) PCR amplification of genomic DNA with specific primers; and (4) analysis of ribotoxic activity. Five new strains, A. clavatus, A. oryzae var. effusus, A. ostianus, A. tamarii, and Neosartorya fischeri var. spinosa, were identified to contain an alpha-sarcin-like ribotoxin. These positive strains exhibit ribotoxic activity by cleaving ribosomes and generating an alpha-fragment.
84Characterization of a new ribotoxin gene (c-sar) from Aspergillus clavatus. Huang K-C ; Hwang Y-Y ; Hwu L ; Lin A Toxicon; 35 (3). 1997. 383-392.A new ribotoxin, c-sarcin, was isolated from a culture of Aspergillus clavatus. A full-length genomic DNA (c-sar) coding for c-sarcin was cloned and sequenced. The deduced amino acid sequence showed a high homology to restrictocin and alpha-sarcin. The native toxin as well as the recombinant protein hydrolysed ribosomes and naked RNA. The genomic structure of the c-sar gene had an intron located between the coding sequences for secretory signal peptide and the mature protein. The intron contained a stretch of 38 adenines. The intron sequence of c-sar was different from that of restrictocin but resembled that of alpha-sarcin. There was 34% identity between the intron of c-sarcin and alpha-sarcin, and this similarity was further increased to 83% if the stretch of polyadenine was omitted
86Four new mycotoxins of Aspergillus clavatus related to tryptoquivaline. Buchi G ; Luk KC ; Kobbe B ; Townsend JM . J Org Chem; 42 (2). 1977 244-246The hydroxylamine nortryptoquivaline (2) and the 3 secondary amines deoxytryptoquivaline (3), deoxynortryptoquivaline (4) and deoxynortryptoquivalone (8) were found to be toxic metabolites of A. clavatus. (The fungus was one of several collected from mold-infested rice found in a Thai household where a child died of an unidentified toxicosis.) They were accompanied by the 2 previously described tremor producing agents tryptoquivaline (1) and nortryptoquivalone (7). The only weakly basic secondary amines 3, 4 and 8 were oxidized to the corresponding hydroxylamines 1, 2 with m-chlorperbenzoic acid.
88Flavipucine and brunnescin, two antibiotics from cultures of the mycophilic fungus Cladobotryum rubrobrunnescens. Wagner C, Anke H, Besl H, Sterner O. Z Naturforsch [C]. 1995 May-Jun;50(5-6):358-64.Two antimicrobial metabolites were isolated from submerged cultures of Cladobotryum rubrobrunnescens, a mycophilic fungus growing on a Inocybe species. One of the compounds proved to be identical to flavipucine (2), an antibiotic previously isolated from Aspergillus flavipes (Casinovi et al., 1968) and from a Macrophoma species (Sassa T. and Onuma Y. (1983), Agric. Biol. Chem. 47, 1155-1157). The other metabolite, brunnescin (1), is a new tetrasubstituted furan derivative which exhibits antibacterial, antifungal and cytotoxic effects.
89Spiroquinazoline, a novel substance P inhibitor with a new carbon skeleton, isolated from Aspergillus flavipes. Barrow CJ, Sun HH. J Nat Prod. 1994 Apr;57(4):471-6.A novel substance P inhibitor, spiroquinazoline [1], was isolated from the fungus Aspergillus flavipes, which was originally obtained from soil. The structure of 1 was determined by analysis of spectroscopic data and 1 was shown to contain a new carbon skeleton containing a spiro-carbon center. Also isolated from the same culture extract were the new natural product, benzodiazepiedione [3], and the known compounds, acyl aszonalenin [4], N-benzoyl-L-phenylalaninol, and seven diketopiperazines.
90 TMC-169, a new antibiotic of the aspochalasin group produced by Aspergillus flavipes.
Kohno J, Nonaka N, Nishio M, Ohnuki T, Kawano K, Okuda T, Komatsubara S.
J Antibiot (Tokyo). 1999/06/01 00:00;52(6):575-7.
98Natural and in vitro coproduction of cyclopiazonic acid and aflatoxins. Martins ML, Martins HM. J Food Prot. 1999 Mar;62(3):292-4.Eighty samples of animal feeds of different origins were screened for the natural co-occurrence of cyclopiazonic acid (CPA) and aflatoxins in Portugal. Forty-five strains of Aspergillus flavus were collected from those samples and studied for their ability to produce these mycotoxins, in vitro. CPA was detected by thin-layer chromatography using Erhlich's reagent for confirmation. Aflatoxins were determined by high-pressure liquid chromatography with postcolumn iodination. Only 5 of the 80 samples (6.2%) were naturally contaminated with cyclopiazonic acid (0.16 mg/kg) and 36 (45.0%) with aflatoxin B1 (AFB1) (from 0.001 to 0.016 mg/kg). An in vitro study of the 45 strains of A. flavus was performed in cracked corn at 25 degrees C (water activity, a(w) = 0.96), incubated for 21 days to CPA production. For in vitro production of aflatoxins, the same substrate was incubated at 28 degrees C for 14 days. Nineteen of the strains (42.2%) produced CPA (ranging from 0.5 to 1.45 mg of CPA/kg) and 23 of them (51.1%) produced AFB1 (from 0.001 to 0.844 mg/kg). Only 10 isolates (22.2%) produced both CPA and AFB1 (0.05 to 0.10 mg/kg and 0.001 to 0.230 mg/kg, respectively). Thirteen strains did not produce either CPA nor AFB1.
99Multiple toxin production by an isolate of Aspergillus flavus. Richard, J L; Gallagher, R T. Richard JL, Gallagher RT. Mycopathologia. 1979 Jul 16;67(3):161-3.Three toxins were recovered from rice and wheat cultures of an isolate of Aspergillus flavus. The toxins were present simultaneously in the cultures after one or two weeks incubation and were identified as aflatoxin, cyclopiazonic acid and aflatrem, a recently identified indole-mevalonate metabolite.
100Microbiological threat from buildings and rooms and its influence on human health (sick building syndrome)] Ochmański W, Barabasz W. Przegl Lek. 2000;57(7-8):419-23.In buildings we can observe many different strains of bacteria, over 400 species of mould fungi, many strains of fungus causing the rotting of wood and wood like materials, many species of algae, aphids, and other types of growths and seed plants and also over 30 types of mites especially those seen in house dust. Buildings, especially their interiors have a very specific microclimate. Within it areas of so called ecological lows are formed in which conditions for settlement, growth and reproduction of these organisms take place. A building, which is a hazard to the health of its residents, is called a "sick building" from the term "sick building syndrome". The incidence and development of some types of mould fungus is associated with the production of very toxic metabolites which are called secondary metabolites i.e. mycotoxins. Long term human, especially in relation to children, contact with the species producing the most potent mycotoxins like aflatoxin--Apergillus flavus, ochratoxins--Aspergillus ochraceus, rubratoxins--Penicillium rubrum or strachybotrytoxins--Strachybotrys chartarum may even be the cause of death. Mould fungus or just mould is a saprophytic fungus derived from many different systemic groups (Mucor, Aspergillus, Penicillium, Fusarium). Fungi can produce lethal mycotoxins such as: alternariol, aflatoxins, gliotoxins, ochratoxins, nivalenol, cytinine, dicumarol, rugulosine, trichoviridine and about 200 more which considering their mutagenicity are potentially dangerous to humans, animals, flora and microorganisms. Research which was begun by Prof. Julian Aleksandrowicz and Prof. Bolesław Smyk in 1970 and 1971 showed that the so called "leukaemia houses" of leukaemia victims had an abundance of toxinogenic fungus in them, particularly the most potent fungus which turned out to be Aspergillus flavus. Toxinogenic funguses are abundant in many living spaces and cellars in older and also in new housing. Mycotoxins have been shown to be very toxic and harmful and it is no wonder that many inhabitants of these living spaces are constantly ill, mainly upper respiratory tract infections, lethargy, constant headaches, nausea and a general ill feeling. Inhabiting these living spaces for a considerable period may lead to cancer.
101Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects. Valdes, J J; Cameron, J E; Cole, R J. Valdes JJ, Cameron JE, Cole RJ. Environ Health Perspect. 1985 Oct;62:459-63.Tremorgenic mycotoxins induce neurologic symptoms ranging from mental confusion to tremors, seizures and death, and are apparently the only class of mycotoxins with significant central nervous system activity. Tremorgens have been implicated in a number of neurologic diseases of cattle collectively known as staggers syndromes, and pose significant agricultural and health problems for both cattle and humans.
102 Aflatrem, the tremorgenic mycotoxin from Aspergillus flavus. Gallagher, R T; Wilson, B J. Gallagher RT, Wilson BJ. Mycopathologia. 1979 Feb 28;66(3):183-5. 
103The biosynthesis of kojic acid by Aspergillus flavus Link strains isolated from feed. Kharchenko SM. Mikrobiol Z. 1999 Jul-Aug;61(4):15-21.An ability of 98 strains of Aspergillus flavus link to form kojic acid has been studied. Fourteen strains with high activity of synthesis (the content of kojic acid in the nutrient medium was 28-32 mg/ml on the 14th day of cultivation) have been selected. The specific kojiforming activity of kojic acid formation of aspergilli strains was maximal during exponential growth phase. Initial value of pH of growth medium providing maximum intensity of kojic acid biosynthesis (4.5-5.5). Such carbohydrates as glucose, saccharose, maltose and galactose proved to be of the most use. Comparatively high yield of kojic acid (8.5-9.5 g/kg) was obtained by the method of solid-phase fermentation on the grain and grain-forage with high amount of proteins and carbohydrates (maize, oats, rye and barley grain). A method of production of crystalline chemically pure kojic acid was modified. The preparation toxicity was studied on chickens. A number of clinical and pathanatomical symptoms characteristic of kojitoxicosis of agricultural animals and poultry have been registered.
104Kojic acid production from cocoa juice by Aspergillus flavus entrapped in calcium alginate. el-Sharkawy SH. Boll Chim Farm. 1995 Jun;134(6):316-9.Sixteen microorganisms of Aspergillus strains were screened for production of kojic acid using cocoa juice as carbon source. Only Aspergillus flavus ATCC 9179 was found to produce the acid in low yield (22 mg/ml). Calcium alginate immobilization of the cells was used under optimum conditions to maximize the yield of kojic acid (60 mg/ml). Cultures were incubated in the medium with 50% of cocoa juice added in pulses of 8 ml each every 96 hours, and 4% methanol, pH 3.5, 150 rpm, 26 degrees C for three weeks. The incubations were monitored by thin layer and high pressure liquid chromatography. Kojic acid was extracted from the culture broth by organic solvent, concentrated and crystallized. The chemical identity of kojic acid was determined by HPLC, MS, 1H- and 13C-NMR spectroscopy.
105Natural occurrence of sterigmatocystin in in-shell pecans. Schroeder HW, Hein H Jr. Can J Microbiol. 1977 May;23(5):639-41.The natural occurrence of sterigmatocystin (S) in in-shell pecans is reported. Aspergillus versicolor was not isolated from contaminated samples. Incidence of A. flavus and A. glaucus, species known to produce sterigmatocystin under laboratory conditions, was high (43 and 35%, respectively). Isolation data suggest sterigmatocystin may have been produced by one or both of these species.
131Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins. Mitchell CG, Slight J, Donaldson K. Thorax. 1997 Sep;52(9):796-801BACKGROUND: The fungus Aspergillus fumigatus, whose spores are present ubiquitously in the air, causes a range of diseases in the human lung. A small molecular weight (< 10 kD) heat stable toxin released from the spores of clinical and environmental isolates of A fumigatus within minutes of deposition in aqueous solution has previously been described. A key effect of the toxin was to inhibit the oxidative burst of macrophages as measured by superoxide anion release. It was hypothesised that the toxin was one of the commonly found A fumigatus hyphal toxins such as gliotoxin. This inhibitor may be an important factor which allows the fungus to colonise the lung. METHODS: The spore derived inhibitor was shown to inhibit the respiratory burst of rat alveolar macrophages, as measured by the generation of superoxide anion. Samples of the spore diffusate were subject to reversed phase high performance liquid chromatography (HPLC), thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), or organic extraction followed by TLC or HPLC to identify the presence of gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C. Commercially obtained preparations of the toxins gliotoxin, fumagillin and helvolic acid and extracts enriched for fumigaclavine-C and aurasperone-C were used as internal and external standards and in the respiratory burst measurements. RESULTS: Gliotoxin, fumagillin, helvolic acid, fumigaclavine-C, and aurasperone-C were not detected in spore derived diffusate using PHLC or TLC. Using extraction procedures with solvents known to extract gliotoxin from A fumigatus culture supernatants, no gliotoxin was detected in the spore derived diffusate. Commercial gliotoxin, fumagillin, and helvolic acid or extracts enriched for fumigaclavine-C and aurasperone-C did not inhibit the oxidative burst of macrophages. CONCLUSIONS: The hypothesis that the spore derived toxin is one of the toxins derived from hyphae such as gliotoxin, helvolic acid, fumagillin, fumigaclavine-C, or aurasperone-C is not proved. The spore toxin may exert its effect through its ability to diffuse rapidly into the lung lining fluid, diminish the macrophage oxidative burst, and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects.
132Effect of phosphate on ergot alkaloid synthesis in Aspergillus fumigatus. Rao KK, Gupta AR, Singh VK. Folia Microbiol (Praha). 1977;22(5):415-9.High concentration of inorganic phosphate in the culture medium of Aspergillus fumigatus inhibited ergot alkaloid synthesis. Addition of L-tryptophan but not mevalonate or 5-methyltryptophan to the above culture restored the alkaloid synthesis to the level found in normal cultures. The decrease in alkaloid synthesis in the fungus accompanies an increase in cell mass, cellular protein and sterol content. Aspartate aminotransferase and alanine aminotransferase activities were significantly increased in the high-phosphate culture.
133 Cell-pool tryptophan levels during ergot alkaloid formation in Aspergillus fumigatus.
Rao KK, Gupta AR. Indian J Exp Biol. 1977 Jul;15(7):588-9.
134Mycotoxins produced by Aspergillus fumigatus isolated from silage.Cole RJ, Kirksey JW, Dorner JW, Wilson DM, Johnson J Jr, Bedell D, Springer JP, Chexal KK, Clardy J, Cox RH. Ann Nutr Aliment. 1977;31(4-6):685-91.Results are presented which show that Aspergillus fumigatus was one of the predominant fungi contaminating moldy silage. Growth of A. fumigatus on silage appeared to depend on a preliminary aerobic fermentation by other natural microflora in silage. The clavine alkaloid, fumigaclavine A, and a new clavine alkaloid designated fumigaclavine C were produced by A. fumigatus. The LD50 of fumigaclavine C was approximately 150 mg/kg oral dose in day-old cockerels.
135Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium. Amitani R, Taylor G, Elezis EN, Llewellyn-Jones C, Mitchell J, Kuze F, Cole PJ, Wilson R. Infect Immun. 1995 Sep;63(9):3266-71.The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.
136Process of fumigatin and spinulosin formation by Aspergillus fumigatus Fres and polarographic assay of these toxins (author's transl)]Ann Microbiol (Paris). 1978 Jul;129B(1):3-18.A strain of Aspergillus fumigatus (Fresenius) isolated from a milk food for calves was grown on a culture medium containing added saccharose. The purpose was to study the synthesis of two recently discovered mycotoxins, fumigatin and spinulosin. The work was performed under many different conditions of temperature, pH and inoculum. These mycotoxins were measured by analytical differential pulse polarography. Correlations were observed between the growth rate of A. fumigatus and variation in pH of the medium and the formation of fumigatin, which is only possible when pH falls to less than 4.0. Fumigatin appears promptly at the beginning of the growth phase of the fungus but quickly disappears. The production of metabolite depends on limited conditions of culture. Spinulosin, very similar to fumigatin, is substituted for fumigatin in slightly different conditions. During growth, the fungus degrades both metabolites. The nature of the substitution and the reason of these modifications have not been investigated. Fumigatin and spinulosin formation is observed in both toxigenic and non-toxigenic strains.
137Fumitoxins, new mycotoxins from Aspergillus fumigatus Fres. Debeaupuis JP, Lafont P.
Appl Environ Microbiol. 1978 Jul;36(1):8-10.
Extracts of cultures of Aspergillus fumigatus isolated from silage were lethal to chicken embryos. Using this test and thin-layer chromatography, four UV-absorbing toxins, designated as fumitoxins A, B, C and D, were isolated. Analysis and mass spectrometry of crystallized fumitoxin A, the most abundant in the extract, established its molecular formula to be C31H42O8. Infrared, UV spectroscopy, and chemical reactions suggested that fumitoxin A is a steroid. Fumitoxins appear to be clearly different from the previously described toxins recognized in A. fumigatus.
138The isolation, purification and identification of fumitremorgin B produced by Aspergillus fumigatus. Liu J, Yang ZJ, Meng ZH. Biomed Environ Sci. 1996 Mar;9(1):1-11.Twenty-six strains of Aspergillus fumigatus were screened for toxigenicity for fumitremorgins A and B. Twenty-three of 26 strains can produce fumitremorgin B in rice medium determined by TLC and HPLC, and no fumitremorgin A was detected. The strains of no. C4104 and no. 3656 were inoculated onto 5 kg of rice media and incubated in a modified procedure. Finally, 4.0 g of fumitremorgin B was obtained after extraction and purification by modified methods, and was confirmed by TLC, HPLC, spectral analysis together with other physicochemical analysis. This is the first report of the preparation of fumitremorgin B in China
139Production of tremorgenic mycotoxins by isolates of Aspergillus fumigatus from sawmills in Sweden. Land CJ, Lundström H, Werner S. Mycopathologia. 1993 Nov;124(2):87-93.One hundred and six strains of A. fumigatus were isolated from 21 sawmills in Sweden, and 73 of these strains were examined for production of fumitremorgen B and verruculogen (tremorgenic mycotoxins) on YES-medium using thin layer chromatography (TLC). Twenty-three strains (32%) were tremorgen producers and 50 strains (68%) were non-producers. Tremorgenic mycotoxins were detected in conidia of seven A. fumigatus strains. The amount of toxin varied between 0.6-8.0 microgram/10(8) conidia (mean value 2.3 micrograms/10(8) conidia, equivalent with 0.18%). No production of the mycotoxin gliotoxin was detected in 6 strains of A. fumigatus. No tremorgens were detected during mould growth on wood substrates, in spite of the use of different wood species (Scots pine, Pinus sylvestris: Norway spruce, Picea abies and birch, Betula spp.), dried versus non-dried wood, bark (pine), leached wood, and wood after various sterilization methods.
140Tremorgenic mycotoxins from Aspergillus fumigatus as a possible occupational health problem in sawmills. Land CJ, Hult K, Fuchs R, Hagelberg S, Lundström H. Appl Environ Microbiol. 1987 Apr;53(4):787-90.Wood-trimmers' disease, generally called extrinsic allergic alveolitis, which affects workers in sawmills, is thought to be caused by fungal diaspores. The importance of Aspergillus fumigatus on the surface of wood dried in kilns is accentuated by its ability to produce tremorgenic mycotoxins. Eight strains of A. fumigatus from five different sawmills were isolated and cultivated on liquid media, and one of the strains was also cultivated on wood blocks. Extracts were prepared, and the tremorgenic reactions were induced by oral administration of extracts to rats. Extracts of the strain grown in liquid medium and on wood blocks induced very strong tremorgenic reactions when administered orally to rats. Four other strains induced mild tremorgenic reactions. High-performance liquid chromatography analysis revealed two tremorgenic mycotoxins, verruculogen and fumitremorgen C, in the five toxic strains. One nontoxic strain produced detectable levels of verruculogen. These results, coupled with the known resemblance of the acutely toxic phase of wood-trimmers' disease to the symptoms produced by these tremorgens, imply that wood-trimmers' disease and similar occupational diseases are, at least in part, mycotoxicoses.
141Isolation and Identification of Aspergillus fumigatus Mycotoxins on Growth Medium and Some Building Materials. Nieminen SM, Kärki R, Auriola S, Toivola M, Laatsch H, Laatikainen R, Hyvärinen A, Von Wright A. Appl Environ Microbiol. 2002 Oct;68(10):4871-4875.Genotoxic and cytotoxic compounds were isolated and purified from the culture medium of an indoor air mold, Aspergillus fumigatus. One of these compounds was identified as gliotoxin, a known fungal secondary metabolite. Growth of A. fumigatus and gliotoxin production on some building materials were also studied. Strong growth of the mold and the presence of gliotoxin were detected on spruce wood, gypsum board, and chipboard under saturation conditions.
142Mycotoxins of Aspergillus fumigatus in pure culture and in native bioaerosols from compost facilities. Fischer G, Müller T, Ostrowski R, Dott W. Chemosphere. 1999 Apr;38(8):1745-55.Exposure to secondary metabolites of airborne fungi in waste handling facilities is discussed in regard to potential toxic impacts on human health. The relevance of mycotoxins has been intensely studied in connection with contamination of food and feed. Toxic secondary metabolites are expected to be present in airborne spores, but exposure to mycotoxins in bioaerosols has not been studied sufficiently. Aspergillus fumigatus is one of the most frequent species in the air of compost plants. A wide range of secondary metabolites was found in pure cultures of freshly isolated strains of A. fumigatus. Tryptoquivaline, a compound with tremorgenic properties, and trypacidin, for which no toxic properties are described, were found in native bioaerosols in a compost facility. The highly toxic metabolites gliotoxin and verruculogen were not found in the bioaerosols.
155Toxicity of echinulin from Aspergillus chevalieri in rabbits. Ali M, Mohammed N, Alnaqeeb MA, Hassan RA, Ahmad HS. Toxicol Lett. 1989 Sep;48(3):235-41.Rabbits were injected intraperitoneally with purified echinulin, a product of Aspergillus chevalieri. After 2 h, the rabbits were bled and enzyme analyses were carried out on the supernates of liver homogenates and citrated plasma. Elevated levels of total plasma lactate dehydrogenase, cardiac derived isozyme, glutamic-oxaloacetic and glutamic-pyruvic transaminase activities in animals receiving toxin were observed. These levels were statistically significant compared to the vehicle control. A significant increase in liver lactate dehydrogenase of toxin-treated rabbits was also observed. Light-microscopic examination of lung and liver showed a significant degree of damage. The increase in plasma enzyme levels is indicative of damage to these organs.
156Eurotium spp. and echinulin in feed refused by swine. Vesonder RF, Lambert R, Wicklow DT, Biehl ML. Appl Environ Microbiol. 1988 Mar;54(3):830-1.Feed refused by swine contained a high-propagule density of Eurotium chevalieri Mangin (anamorph, Aspergillus chevalieri (Mangin) Thom and Church), Eurotium amstelodami Mangin (anamorph, Aspergillus amstelodami (Mangin Thom and Church), and Aspergillus candidus Link. Echinulin (8 micrograms/g of feed) was detected in the feed. Isolates of E. chevalieri and E. amstelodami but not A. candidus produced echinulin on rice or cracked corn. Mice refused to drink water containing 90 micrograms of echinulin per ml. This is the first report of the alkaloid echinulin in feed refused by swine.
157Eurotium (Aspergillus) repens metabolites and their biological activity. Podojil M, Sedmera P, Vokoun J, Betina V, Barathova H, Durackova Z, Horakova K, Nemec P. Folia Microbiol (Praha). 1978;23(6):438-43.Eurotium repens mycelium cultivated under static conditions was used to isolate and identify metabolities--echinulin, physcion, erythroglaucin, flavoglaucin and asperentin; the filtrate of the culture yielded asperentin 8-methylether. The broadest biological activity spectrum was displayed by asperentin which had antibacterial and antifungal effects and, at a concentration of 86 microgram/ml, caused 50% mortality in Artemia saline larvae. The highest cytotoxicity towards HeLa cells was found in physcion which caused 50% growth inhibition at a concentration of 0.1 microgram/ml.
158Toxicity and mutagenicity of anthraquinones from Aspergillus chevalieri. Bachmann M, Blaser P, Lüthy J, Schlatter C. J Environ Pathol Toxicol Oncol. 1992 Mar-Apr;11(2):49-52.More than 100 strains of the Aspergillus glaucus group were cultivated on synthetic media for 11 days at 28 degrees C. Organic extracts of fungal material were screened by thin-layer chromatography (TLC) for the mycotoxins aflatoxins B1,2 and G1,2, sterigmatocystin, ochratoxin A, gliotoxin, patulin, and xanthocillin X. None of these toxins were produced in detectable amounts under experimental conditions. Nevertheless, organic extracts exhibited high toxicity after intraperitoneal (i.p.) administration in mice. Aspergillus chevalieri strain ZT 8268 was selected for further investigation of its toxic metabolites. The main toxic action was attributed to the four anthraquinone derivatives, physicion, physcionanthrone B, physciondianthrone, and erythroglaucin, which were isolated and identified. No toxic effects were found after oral administration. Using the Salmonella/mammalian microsome test, mutagenic activity (frame-shift) was detected in strain TA 1537 in the presence of S-9 liver microsome preparation.
159 Ochratoxin A formation by isolated strains of the conidial stage of Aspergillus glaucus Link ex Grey (= Eurotium herbariorum Wiggers Link ex Gray) from cereal grains. Chełkowski J, Samson RA, Wiewiórowska M, Goliński P. Nahrung. 1987;31(4):267-9.Two strains of Aspergillus glaucus Link ex Grey (= Eurotium herbariorum (Wiggers Link ex Grey] out of 15 isolated from cereals formed ochratoxin A during growth on autoclaved kernels of wheat and corn, with yields from 0.8 to 2.5 mg/kg of culture.
160Natural occurrence of sterigmatocystin in in-shell pecans. Schroeder HW, Hein H Jr. Can J Microbiol. 1977 May;23(5):639-41.The natural occurrence of sterigmatocystin (S) in in-shell pecans is reported. Aspergillus versicolor was not isolated from contaminated samples. Incidence of A. flavus and A. glaucus, species known to produce sterigmatocystin under laboratory conditions, was high (43 and 35%, respectively). Isolation data suggest sterigmatocystin may have been produced by one or both of these species.
164 Nidulotoxin: the toxin of Aspergillus nidulans Wint] Lafont P, Lafont J, Frayssinet C.
Experientia. 1970 Jan 15;26(1):61-2.
165Molecular regulation of penicillin biosynthesis in Aspergillus (Emericella) nidulans. Brakhage AA. FEMS Microbiol Lett. 1997 Mar 1;148(1):1-10.The beta-lactam antibiotic penicillin is produced as end product by only some filamentous fungi, most notably by Aspergillus nidulans and Penicillium chrysogenum. The biosynthesis of this secondary metabolite is catalyzed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aat (penDE). The genes are organized into a gene cluster. In A. nidulans, several studies have indicated that the genes are controlled by a complex regulatory network. The wide-domain regulatory protein PACC binds to the intergenic region between acvA and ipnA and, at alkaline pH, increases at least ipnA gene transcription. An additional DNA binding protein (PENR1) was suggested to repress acvA and to activate ipnA and aat expression. Furthermore, three recessive trans-acting mutations have been characterized (prgA1, prgB1, npeE1) which most likely correspond to positively acting regulatory genes of the penicillin biosynthesis genes.
166Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide synthase. Yu JH, Leonard TJ. J Bacteriol. 1995 Aug;177(16):4792-800.A filamentous fungus, Aspergillus nidulans, produces the carcinogenic mycotoxin sterigmatocystin (ST), which is a polyketide-derived secondary metabolite. A gene (pksST) encoding the ST polyketide synthase (PKSst) in A. nidulans was cloned, sequenced, and characterized. Large induced deletion mutants, which did not make ST or any ST intermediates, were used to identify genes associated with ST biosynthesis. Among the transcripts detected within the deletion region, which showed developmental expression with ST production, was a 7.2-kb transcript. Functional inactivation of the gene encoding the 7.2-kb transcript blocked production of ST and all ST intermediate substrates but did not affect transcription of the pathway genes, indicating that this gene was involved in a very early step of ST biosynthesis. These results also indicate that PKSst was not associated with activation of other ST genes. Sequencing of the region spanning this gene revealed that it encoded a polypeptide with a deduced length of 2,181 amino acids that had high levels of similarity to many of the known polyketide synthases and FASs. This gene, pksST, encodes a multifunctional novel type I polyketide synthase which has as active sites a beta-ketoacyl acyl carrier protein synthase, an acyltransferase, duplicated acyl carrier proteins, and a thioesterase, all of these catalytic sites may be multiply used. In addition, a 1.9-kb transcript, which also showed developmental expression, was mapped adjacent to pksST, and the sequence of this gene revealed that it encoded a cytochrome P-450 monooxygenase-like peptide.
178Structure of malformin B, a phytotoxic metabolite produced by Aspergillus niger. Kim KW, Sugawara F, Yoshida S, Murofushi N, Takahashi N, Curtis RW. Biosci Biotechnol Biochem. 1993 May;57(5):787-91.Malformin B, produced by Aspergillus niger, was separated into six compounds by HPLC. Their structures were determined by amino acid analyses, and by mass spectral and two-dimensional NMR experiments to be cyclic pentapeptides structurally related to malformin A1. Both the NMR and MS/MS experiments suggest cyclo-D-cysteinyl-D-cysteinyl-L-amino acid-D-amino acid-L-amino acid as the essential structure of malformins.
179 Production and antibacterial activity of malforming C, a toxic metabolite of Aspergillus niger. Kobbe B, Cushman M, Wogan GN, Demain AL. Appl Environ Microbiol. 1977 Apr;33(4):996-7.The production of the new mycotoxin malformin C by a solid substrate fermentation is described. Malformin C is highly toxic (mean lethal dose = 0.9 mg/kg) and exerts antibacterial activity against a variety of gram-positive and gram-negative organisms.
180On the safety of Aspergillus niger - a review2Schuster E, Dunn-Coleman N, Frisvad JC, VanDijck PW. Appl Microbiol Biotechnol. 2002 Aug;59(4-5):426-35.Aspergillus niger is one of the most important microorganisms used in biotechnology. It has been in use already for many decades to produce extracellular (food) enzymes and citric acid. In fact, citric acid and many A. niger enzymes are considered GRAS by the United States Food and Drug Administration. In addition, A. niger is used for biotransformations and waste treatment. In the last two decades, A. niger has been developed as an important transformation host to over-express food enzymes. Being pre-dated by older names, the name A. niger has been conserved for economical and information retrieval reasons and there is a taxonomical consensus based on molecular data that the only other common species closely related to A. niger in the Aspergillus series Nigri is A. tubingensis. A. niger, like other filamentous fungi, should be treated carefully to avoid the formation of spore dust. However, compared with other filamentous fungi, it does not stand out as a particular problem concerning allergy or mycopathology. A few medical cases, e.g. lung infections, have been reported, but always in severely immunocompromised patients. In tropical areas, ear infections (otomycosis) do occur due to A. niger invasion of the outer ear canal but this may be caused by mechanical damage of the skin barrier. A. niger strains produce a series of secondary metabolites, but it is only ochratoxin A that can be regarded as a mycotoxin in the strict sense of the word. Only 3-10% of the strains examined for ochratoxin A production have tested positive under favourable conditions. New and unknown isolates should be checked for ochratoxin A production before they are developed as production organisms. It is concluded, with these restrictions, that A. niger is a safe production organism.
181Potential ochratoxin A producers from wine grapes in Argentina and Brazil. Da RR, Palacios V, Combina M, Fraga ME, De OR, Magnoli CE, Dalcero AM. Food Addit Contam. 2002 Apr;19(4):408-14.The aim was to identify the normal mycoflora in wine grapes from Argentina and Brazil. We collected 50 grapes samples from Malbec and Chardonnay varieties in each country during the 1997-98 harvest. Yeasts were a major component of the fungal population, and the most frequent genera of filamentous fungi isolated were: Aspergillus, Penicillium and Botrytis. Other genera identified (in decreasing order) were: Phythophthora, Moniliella, Alternaria and Cladosporium. From grapes, the mean frequency of filamentous fungi ranged from 1.3 x 10(4) to 5.4 x 10(6) CFU g(-1). We isolated 48 Aspergillus niger strains from Argentinian grape, of which eight could produce ochratoxin A. Sixteen of 53 A. niger strains from Brazilian grapes produced ochratoxin A. The results indicate that similar mycobiota were isolated from Argentinian and Brazilian wine grapes and there could be ochratoxin A production in this substrate.
182Construction and characterization of an oxalic acid nonproducing strain of Aspergillus niger. Pedersen H, Christensen B, Hjort C, Nielsen J. Metab Eng. 2000 Jan;2(1):34-41.Aspergillus niger produces oxalic acid as a by-product which causes problems with downstream processing of industrial enzymes. To overcome this problem the oah gene encoding oxaloacetate hydrolase (EC was disrupted in a glucoamylase-producing strain of A. niger and the resulting strain was incapable of producing oxalic acid. The strain with the disrupted gene was compared with the wild-type strain producing oxalic acid in batch cultivations. The specific growth rate of both strains was 0.20 h(-1). The citric acid yields were identical, but the glucoamylase yield was only 50% in the disruptant compared with the wild-type strain. Batch experiments with 13C-labeled glucose as substrate were carried out to determine the metabolic fluxes through the central metabolism. The two strains had almost identical metabolic fluxes, which suggested that it was possible to disrupt the oah gene without pleiotropic consequences. The flux through the pentose phosphate pathway was around 60% of the glucose uptake for both strains, which suggested that a sufficient supply of NADPH was available for biosynthesis.
193Ochratoxin production by the Aspergillus ochraceus group and Aspergillus alliaceus. Bayman P, Baker JL, Doster MA, Michailides TJ, Mahoney NE. Appl Environ Microbiol. 2002 May;68(5):2326-9.Ochratoxin A is a toxic and carcinogenic fungal secondary metabolite; its presence in foods is increasingly regulated. Various fungi are known to produce ochratoxins, but it is not known which species produce ochratoxins consistently and which species cause ochratoxin contamination of various crops. We isolated fungi in the Aspergillus ochraceus group (section Circumdati) and Aspergillus alliaceus from tree nut orchards, nuts, and figs in California. A total of 72 isolates were grown in potato dextrose broth and yeast extract-sucrose broth for 10 days at 30 degrees C and tested for production of ochratoxin A in vitro by high-pressure liquid chromatography. Among isolates from California figs, tree nuts, and orchards, A. ochraceus and Aspergillus melleus were the most common species. No field isolates of A. ochraceus or A. melleus produced ochratoxin A above the level of detection (0.01 microg/ml). All A. alliaceus isolates produced ochratoxin A, up to 30 microg/ml. We examined 50,000 figs for fungal infections and measured ochratoxin content in figs with visible fungal colonies. Pooled figs infected with A. alliaceus contained ochratoxin A, figs infected with the A. ochraceus group had little or none, and figs infected with Penicillium had none. These results suggest that the little-known species A. alliaceus is an important ochratoxin-producing fungus in California and that it may be responsible for the ochratoxin contamination occasionally observed in figs.
194Ochratoxin A in airborne dust and fungal conidia. Skaug MA, Eduard W, Størmer FC. Mycopathologia. 2001;151(2):93-8.Farm workers are often exposed to high concentrations of airborne organic dust and fungal conidia, especially when working with plant materials. The purpose of this investigation was to study the possibility of exposure to the mycotoxin ochratoxin A (OTA) through inhalation of organic dust and conidia. Dust and aerosol samples were collected from three local cowsheds. Aerosol samples for determination of total conidia and dust concentrations were collected by stationary sampling on polycarbonate filters. Total dust was analysed by gravimetry, and conidia were counted using scanning electron microscopy. A method was developed for extraction and determination of OTA in small samples of settled dust. OTA was extracted with a mixture of methanol, chloroform, HCl, and water, purified on immunoaffinity column, and analysed by ion-pair HPLC with fluorescence detection. Recovery of OTA from spiked dust samples (0.9-1.0 microg/kg) was 74% (quantitation limit 0.150 microg/kg). OTA was found in 6 out of 14 settled dust samples (0.2-70 microg/kg). The total concentration of airborne conidia ranged from < 1.1 x 10(4) to 3.9 x 15(5) per m3, and the airborne dust concentration ranged from 0.08 to 0.21 mg/m3. Conidia collected from cultures of Penicillium verrucosum and Aspergillus ochraceus contained 0.4-0.7 and 0.02-0.06 pg OTA per conidium, respectively. Testing of conidial extracts from these fungi in a Bacillus subtilis bioassay indicated the presence of toxic compounds in addition to OTA. The results show that airborne dust and fungal conidia can be sources of OTA. Peak exposures to airborne OTA may be significant, e.g., in agricultural environments.
195 Production of penicillic acid and ochratoxin A on poultry feed by Aspergillus ochraceus: temperature and moisture requirements. Bacon CW, Sweeney JG, Robbins JD, Burdick D. Appl Microbiol. 1973 Aug;26(2):155-60. 
196 Bioproduction of ochratoxin A and penicillic acid by members of the Aspergillus ochraceus group.Ciegler A. Can J Microbiol. 1972 May;18(5):631-6. 
202A single amino acid substitution in ribonucleolytic toxin restrictocin abolishes its specific substrate recognition activity. Nayak SK, Batra JK. Biochemistry. 1997 Nov 4;36(44):13693-9.Restrictocin is a small basic protein produced by the fungus Aspergillus restrictus. It potently inhibits protein synthesis in eukaryotic cells by specifically cleaving a single phosphodiester bond in 28S rRNA. A histidine residue at position 49 in restrictocin has been implicated in its active site. A mutant of restrictocin in which the histidine at position 49 was changed to an alanine was constructed by site-directed mutagenesis, and the protein was expressed in Escherichia coli. The mutant and the wild type proteins were found to be structurally identical. Unlike restrictocin, the restrictocin H49A mutant did not cleave the ribosomal RNA specifically at the target phosphodiester bond; instead, it extensively degraded the RNA substrate with altered specificity. The mutant exhibited a high ribonuclease activity compared to restrictocin on yeast tRNA, and poly(U) and poly(C). The mutant also poorly inhibited protein synthesis in eukaryotic cells as well as in a cell free system. We therefore propose that histidine 49 of restrictocin is not involved per se in the enzymatic activity; however, it does play a crucial role in the specific recognition of the target sequence by restrictocin.
203Production and localization of restrictocin in Aspergillus restrictus. Brandhorst TT, Kenealy WR. J Gen Microbiol. 1992 Jul;138 ( Pt 7):1429-35.The production and secretion of restrictocin (a cytotoxin that cleaves ribosomal RNA) by cultures of the fungus Aspergillus restrictus was investigated. Previous studies have indicated that restrictocin production in liquid culture coincides with the appearance of differentiated cell structures. A study of the correlation between the appearance of differentiated structures and restrictocin production was conducted with A. restrictus grown on agar medium. Restrictocin was found to be associated with the cell mass of the agar-grown culture (in contrast to liquid cultures), and was first observed when aerial hyphae emerged. Restrictocin levels increased until the time of conidiation, after which they fell off sharply. No restrictocin could be found in the agar medium. The presence of restrictocin upon and within various cell structures was determined by immunofluorescent laser microscopy. This study showed that restrictocin became localized to the conidiophores and phialides during the process of conidiation. Prior to this, restrictocin was found within the hyphae in localized concentrations that may correspond to secretory vesicles.
204Regulation of restrictocin production in Aspergillus restrictus. Yang R, Kenealy WR. J Gen Microbiol. 1992 Jul;138 ( Pt 7):1421-7.The production of restrictocin (a cytotoxin that specifically cleaves ribosomal RNA) by cultures of Aspergillus restrictus grown in liquid medium was investigated. The function of restrictocin, the method of its accumulation and the mode of resistance to restrictocin in A. restrictus are unknown. Previous studies have indicated that restrictocin accumulates in the medium with culture age. These observations have been extended in this study by cloning the cDNA of the res gene and using this cDNA clone to probe the onset of messenger RNA synthesis in the cells. The results of the Northern analysis were compared to the production and accumulation of restrictocin and morphological differentiation of the cells in culture. Restrictocin was found in the medium at the same time that mRNA was detected in the cells. This suggests that the leader sequence encoded by the cDNA provides an efficient secretion system for the protein. Both the protein and the mRNA were detected coincident with the formation of differentiated cell structures. These structures develop into conidiophores with one layer of sterigmata and conidia forming from the sterigmata. These results suggest that restrictocin is either involved
209Deoxymulundocandin--a new echinocandin type antifungal antibiotic. Mukhopadhyay T, Roy K, Bhat RG, Sawant SN, Blumbach J, Ganguli BN, Fehlhaber HW, Kogler H. J Antibiot (Tokyo). 1992 May;45(5):618-23.A new echinocandin type antifungal antibiotic, deoxymulundocandin, C48H77N7O15, was isolated from the culture filtrate and mycelia of a fungal culture, Aspergillus sydowii (Bainier and Sartory) Thom and Church var. nov. mulundensis Roy (Culture No. Y-30462). The structure was established by comparative GC-MS analyses of the derivatized acid hydrolysates of deoxymulundocandin and mulundocandin as well as by the high field NMR experiments (COSY, NOESY and DEPT).
214Influences of chemical fertilizers (in vitro) on aflatoxin and citrinin synthesis by two strains of aspergilli. Hasan HA, Issa AA. Folia Microbiol (Praha). 1993;38(6):456-8.The selective effect of various levels of phosphate and nitrate (as fertilizers) on biosynthesis of aflatoxin by Aspergillus parasiticus var. globosus, and citrinin by A. terreus var. aureus was studied in defined culture medium. Phosphate at 35-175 mmol per 50 mL decreased aflatoxin production, but increased citrinin synthesis. Nitrate at 73-365 mmol per 50 mL stimulated the synthesis of aflatoxin but depressed that of citrinin. A rise in the levels of nitrate and phosphate led to a decrease in aflatoxin production, an increase in citrinin production and an accumulation of mycelial phosphate and nitrate contents.
215 Citreoviridins from Aspergillus terreus. Franck B, Gehrken HP. Angew Chem Int Ed Engl. 1980;19(6):461-2. 
216Isolation, chemical structure, acute toxicity, and some physicochemical properties of territrem B' from Aspergillus terreus. Peng FC, Ling KH, Wang Y, Lee GH. Appl Environ Microbiol. 1985 Mar;49(3):721-3.We have isolated a metabolite of territrem, designated territrem B', from the chloroform extract of a rice culture of Aspergillus terreus 23-1 by using the same isolation procedure as that for territrems A, B, and C. The present isolation procedure gave about 10 mg of territrem B' from 4 kg of rice culture per batch. Analysis of the high-resolution mass spectrum showed that the molecular composition of territrem B' is C29H34O10 (found, 542.2167; required, 542.200). Some results of physicochemical and acute tests are presented in this paper. Single-crystal X-ray diffractometry of territrem B' indicated that the three-dimensional structure of territrem B' has not changed significantly from that of territrem B except for the insertion of one oxygen atom into territrem B to make an additional pyron ring in the E ring. The tremorgenic activity of territrem B' is greatly reduced as tested by intraperitoneal injection in mice.
217Territrems, tremorgenic mycotoxins of Aspergillus terreus. Ling KH, Yang CK, Peng FT.
Appl Environ Microbiol. 1979 Mar;37(3):355-7
The tremorgenic mycotoxins isolated from Aspergillus terreus were given the trivial names territrem A and B instead of their previous designations of C1 and C2 respectively. High-resolution mass spectral data suggested the molecular formula of territrem A to be C28H30O9 and that of territrem B,C29H34O9. They were partially characterized by ultraviolet, infrared, proton magnetic resonance, and mass spectroscopy. The spectroscopic evidence indicated that their chemical structures were very similar. The procedures of purification were also revised for the complete separation of these two chemically related compounds.
218Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH. J Biol Chem. 1999 Dec 3;274(49):34916-23.Territrem B (TRB) is a fungal metabolite isolated from Aspergillus terreus shown previously to be a potent and irreversible inhibitor of acetylcholinesterase (AChE). In the present study, a number of binding and inhibition assays were carried out to further characterize the inhibitory effect of TRB. The results indicate that the binding of TRB (a) is much more selective than a well characterized selective inhibitor of AChE, BW284C51, (b) adopts a one-to-one stoichiometry with the enzyme, (c) cannot be undone by an AChE-regenerating oxime agent, which contrasts the ability of 8 M urea to release AChE-bound TRB, (d) is enhanced by high concentration NaCl but prevented, unless preincubated, by Triton X-100, and (e) exhibits quasi-first order kinetics with an overall inhibition constant of 0.01 nM(-1) min(-1). Together these results suggest a very different irreversible binding (a noncovalent type) from that of the covalent type, which involves typical irreversible AChE inhibitors such as diisopropylfluorophosphate and neostigmine. According to the prediction of a molecular modeling study, the distinct AChE inhibitory characteristics of TRB may arise from the inhibitor being noncovalently trapped within a unique active-site gorge structure of the enzyme. It was predicted that an optimal TRB. AChE binding would position a narrowing connection of the TRB structure at a constricted area near the entrance of the gorge, thereby providing a structural basis for the observed irreversible binding.
224 Constitution and absolute configuration of austdiol, the main toxic metabolite from Aspergillus ustus. Vleggaar R, Steyn PS, Nagel DW. J Chem Soc [Perkin 1]. 1974;1:45-9. 
225 Austocystins. Six novel dihydrofuro (3',2':4,5)furo(3,2-b)xanthenones from Aspergillus ustus. Steyn PS, Vleggaar R. J Chem Soc [Perkin 1]. 1974;(19):2250-6. 
226 Austin, a novel polyisoprenoid mycotoxin from Aspergillus ustus. Chexal KK, Spinger JP, Clardy J, Cole RJ, Kirksey JW, Dorner JW, Cutler HG, Strawter BJ. J Am Chem Soc. 1976 Oct 13;98(21):6748. 
227 New species of Aspergillus producing sterigmatocystin. Rabie CJ, Steyn M, van Schalkwyk GC. Appl Environ Microbiol. 1977 May;33(5):1023-5. 
233Averufin, an anthraquinone mycotoxin possessing a potent uncoupling effect on mitochondrial respiration. Kawai K, Nozawa Y, Maebayashi Y, Yamazaki M, Hamasaki T. Appl Environ Microbiol. 1984 Mar;47(3):481-3.Averufin and averufin dimethylether from Aspergillus versicolor were examined for their uncoupling effects on oxidative phosphorylation in isolated rat liver mitochondria to get insight into the mode of toxic action of averufin. Averufin uncoupled oxidative phosphorylation, causing 50% uncoupling at about 1.5 microM with respect to the decrease in P/O ratio. Averufin dimethylether did not uncouple but inhibited state 3 respiration of mitochondria, which was not released by either 2,4-dinitrophenol or averufin.
234Production and characterization of sterigmatocystin. Lou JL, Meng ZH, Wang DS. Biomed Environ Sci. 1994 Dec;7(4):293-301.Fourteen strains of Aspergillus versicolor and 2 strains of A. nidulans were screened for sterigmatocystin (ST) production on a semi-synthetic solid substrate by high performance liquid chromatography (HPLC) analysis. Two strains of A. versicolor producing ST at 550.5 substrate and 1160.8 substrate were selected to inoculate 4 kg solid ST-producing media. After 30 days stationary incubation at 28 degrees C in the dark, 2271.6 mg of pale-yellow needle-shaped crystals were isolated and purified from the culture with a procedure applying column chromatography and recrystallization method. The crystal was proved to be sterigmatocystin by spectroanalysis and some physico-chemical analysis. The purity of the final material obtained were more than 99.9% as shown by HPLC and TLC detection. With this procedure, ST was obtained at about one tenth of its commercial cost.
235Mycotoxin-producing potential of mold flora of dried beans. Mislivec PB, Dieter CT, Bruce VR. Appl Microbiol. 1975 Apr;29(4):522-6.To evaluate the potential for mycotoxin production by molds in dried beans, the mold flora of 114 samples was determined both before and after surface disinfection of the beans with 5% NaOCl. Surface disinfection substantially reduced mold incidence, indicating that contamination was mainly on the surface. The flora, both before and after disinfection, was dominated by species of the Aspergillus glaucus group, the toxicogenic species A ochracues, Penicillium cyclopium, and P. viridicatum, and species of Alternaria, Cladosporium, and Fusarium. The toxicogenic species Aspergillus flavis, A. versicolor, Penicillium Citrinum, P. expansum, P. islandicum, and P. urticae were encountered less frequently. Of 209 species of Aspergillus and Penicillium screened for mycotoxin production on sterile rice substrate, 114 produced one or more of the following mycotoxins: A. flavus, aflatoxins; A. ochraceus, ochratoxins; A. nidulans, A. unguis, and A. versicolor, sterigmatocystin; P. cyclopium, penicillic acid; P. citrinum and P. viridicatum, citrinin; P. urticae, patulin and griseofulvin. Sterigmatocystin production by A. unguis is reported for the first time.
236 Occurrence of Toxigenic Aspergillus versicolor Isolates and Sterigmatocystin in Carpet Dust from Damp Indoor Environments. Engelhart S, Loock A, Skutlarek D, Sagunski H, Lommel A, Färber H, Exner M. Appl Environ Microbiol. 2002 Aug;68(8):3886-90. 
237Production of sterigmatocystin by Aspergillus versicolor and Bipolaris sorokiniana on semisynthetic liquid and solid media. Rabie CJ, Lubben A, Steyn M. Appl Environ Microbiol. 1976 Aug;32(2):206-8.Higher yields of sterigmatocystin were obtained with Aspergillus versicolor than with Bipolaris sorokiniana both in liquid and on solid media. The optimum temperature for sterigmatocystin production by A. versicolor was 27 to 29 degrees C and 23 degrees C for B. sorokiniana. In liquid shake cultures, production of sterigmatocystin by B. sorokiniana was negligible, whereas maximal production by A. versicolor was 210 mg/liter. On solid substrates, the highest yields (8 g/kg) were obtained with A. versicolor on still cultures of whole corn supplemented with Soytone.
238Mycotoxins in Crude Building Materials from Water-Damaged Buildings. Tapani Tuomi, Kari Reijula, Tom Johnsson,1 Kaisa Hemminki,
Eeva-Liisa Hintikka, Outi Lindroos, Seija Kalso, Pirkko Koukila-Ka¨hKo¨la¨ , Helena Mussalo-Rauhamaa, and Tari Haahtela. Applied and Environmental Microbiology - May 2000, p. 1899-1904 Vol. 66, No. 5
We analyzed 79 bulk samples of moldy interior finishes from Finnish buildings with moisture problems for 17 mycotoxins, as well as for fungi that could be isolated using one medium and one set of growth conditions. We found the aflatoxin precursor, sterigmatocystin, in 24% of the samples and trichothecenes in 19% of the
samples. Trichothecenes found included satratoxin G or H in five samples; diacetoxyscirpenol in five samples; and 3-acetyl-deoxynivalenol, deoxynivalenol, verrucarol, or T-2-tetraol in an additional five samples. Citrinine was found in three samples. Aspergillus versicolor was present in most sterigmatocystin-containing samples, and Stachybotrys spp. were present in the samples where satratoxins were found. In many cases, however, the presence of fungi thought to produce the mycotoxins was not correlated with the presence of the expected compounds. However, when mycotoxins were found, some toxigenic fungi usually were present, even if the species originally responsible for producing the mycotoxin was not isolated. We conclude that the identification and enumeration of fungal species present in bulk materials are important to verify the severity of mold damage but that chemical analyses are necessary if the goal is to establish the presence of mycotoxins in moldy materials.
239 Anthraquinones in the biosynthesis of sterigmatocystin by Aspergillus versicolor. Hsieh DP, Singh R, Yao RC, Bennett JW. Appl Environ Microbiol. 1978 May;35(5):980-2.14C-labeled averufin, versiconal hemiacetal acetate, and versicolorin A were efficiently converted to sterigmatocystin by Aspergillus versicolor, thus providing experimental evidence that these anthraquinones are biosynthetic precursors of sterigmatocystin, a xanthone.
240Development of molecular tools for the mulundocandin producer Aspergillus sydowii: DNA-mediated transformation and reporter gene expression.Schmitt EK, Eilinghoff B, Olliger R, Decker H, Kuck U. Appl Microbiol Biotechnol. 2002 Apr;58(5):625-31.The echinocandin-type antimycotic mulundocandin and its derivatives are produced by the filamentous fungus Aspergillus sydowii (strain FH2551). These agents have been considered as a potential drug to treat immunocompromised patients who suffer from severe opportunistic fungal infections. In order to generate strains with a modified mulundocandin biosynthesis, we developed molecular tools for genetic engineering of A. sydowii as an alternative to conventional strain improvement procedures. For our experiments, we used strain FH2551, which was discriminated from other Aspergillus strains by determining the sequence of the two internal transcribed spacers (ITS1 and ITS2) of the rDNA locus. In addition, the electrophoretic karyotype of A. sydowii was established using pulsed-field gel electrophoresis (PFGE), leading to a calculated genomic size of about 40 Mb. For gene mapping, chromosomes were subjected to PFGE either unrestricted or after incubation with rare cutting enzymes and probed with heterologous genes. Using the bacterial hygromycin B phosphotransferase gene as a selectable marker for transformation of A. sydowii, we generated transformants with single and multiple copies of plasmid DNA. Subsequently, the heterologous lacZ and gfp genes were efficiently transferred and expressed in A. sydowii. The majority of lacZ-transformants showed more than 6 pkat beta-galactosidase activity/mg protein, while the control strains had no significant background activity. Fluorescence microscopy of gfp-transformants demonstrated that the green-fluorescent protein is present in a stable and active form in the cytoplasm of vegetative hyphae and conidiospores.
242On ochratoxin A and fungal flora in Polish cereals from conventional and ecological farms - Part 1: occurrence of ochratoxin A and fungi in cereals in 1997. Czerwiecki L, Czajkowska D, Witkowska-Gwiazdowska A. Food Addit Contam. 2002 May;19(5):470-7.Over 200 samples of Polish cereal grain from the 1997 harvest obtained from conventional and ecological farms were tested for the presence of ochratoxin A as well as for contamination by microscopic fungi. Ochratoxin A contamination of rye from ecological farms was over six times more frequent than that from conventional cultivation. The ochratoxin A content in wheat and barley samples from ecological farms was also higher. No wheat sample from conventional farms contained the mycotoxin. In the group of ecological farms, there were differences in the percentage of cereal samples containing ochratoxin A. The ochratoxin A levels ranged from 0.2 to 57 microg kg(-1). The mean concentration of ochratoxin A in investigated cereal grain was 5.7 microg kg(-1). From samples containing detectable amounts of ochratoxin A, fungi producing ochratoxin A under laboratory conditions were isolated. They were classified as belonging to the species Penicillium cyclopium, P. viridicatum, P. chrysogenum and also Aspergillus alliaceus, A. versicolor, A. glaucus and A. flavus. Penicillium strains - producers of ochratoxin A - were isolated from 93% of the samples; in 7% of samples, only Aspergillus strains producing this mycotoxin were noted. Rye samples mainly from one farm with an ecological type of cultivation and from one conventional farm were contaminated with both Aspergillus and Penicillium mycotoxigenic strains.
243Microfungal contamination of damp buildings--examples of risk constructions and risk materials. Gravesen S, Nielsen PA, Iversen R, Nielsen KF. Environ Health Perspect. 1999 Jun;107 Suppl 3:505-8.To elucidate problems with microfungal infestation in indoor environments, a multidisciplinary collaborative pilot study, supported by a grant from the Danish Ministry of Housing and Urban Affairs, was performed on 72 mold-infected building materials from 23 buildings. Water leakage through roofs, rising damp, and defective plumbing installations were the main reasons for water damage with subsequent infestation of molds. From a score system assessing the bioavailability of the building materials, products most vulnerable to mold attacks were water damaged, aged organic materials containing cellulose, such as wooden materials, jute, wallpaper, and cardboard. The microfungal genera most frequently encountered were Penicillium (68%), Aspergillus (56%), Chaetomium (22%), Ulocladium, (21%), Stachybotrys (19%) and Cladosporium (15%). Penicillium chrysogenum, Aspergillus versicolor, and Stachybotrys chartarum were the most frequently occurring species. Under field conditions, several trichothecenes were detected in each of three commonly used building materials, heavily contaminated with S. chartarum. Under experimental conditions, four out of five isolates of S. chartarum produced satratoxin H and G when growing on new and old, very humid gypsum boards. A. versicolor produced the carcinogenic mycotoxin sterigmatocystin and 5-methoxysterigmatocystin under the same conditions.
244Synthesis of sterigmatocystin on a chemically defined medium by species of Aspergillus and Chaetomium. Barnes SE, Dola TP, Bennett JW, Bhatnagar D. Mycopathologia. 1994 Mar;125(3):173-8.Sterigmatocystin (ST) is a secondary metabolite and a principal mycotoxin known to be produced by over 30 species of filamentous fungi. It is also one of the late intermediates in aflatoxin biosynthesis. We have tested the ability of 7 species of Aspergillus, including 4 strains of A. versicolor, one species of Bipolaris, and two species of Chaetomium, to produce ST on a sucrose-salts-phenylalanine defined medium as well as on three complex substrates. Highest ST production in our survey was by a strain of A. versicolor grown on wheat, whereas, the highest ST production on defined medium was by C. cellulolyticum. To our knowledge, this is the first report of ST production by C. cellulolyticum on any substrate. In precursor feeding studies, resting cultures of wild type A. nidulans and A. versicolor were unable to biotransform O-methylsterigmatocystin (OMST), the last known intermediate in aflatoxin biosynthesis. These results suggest that ST is the end product of polyketide metabolism in the strains tested.
245 Multiplicity of antibiotic production in Aspergillus versicolor N5 under mutagenesis: versilin a new antifungal antibiotic. Basu S, Das SK, Majumdar S, Bose SK. Indian J Exp Biol. 1987 Mar;25(3):207-8. 
246Mycoversilin, a new antifungal antibiotic. II. Structure elucidation. Samanta AK, Bose SK, Mahato SB. J Antibiot (Tokyo). 1984 Jul;37(7):733-7.The structure of a new antifungal antibiotic, mycoversilin, produced by Aspergillus versicolor (N5)17 was determined as I by various spectroscopic and chemical methods. Mycoversilin is a unique polynuclear aromatic compound having two methyl and six hydroxyl groups and two ether linkages. The acetyl derivative prepared was found to have no antifungal property.
247Mycoversilin, a new antifungal antibiotic. I. Fermentation, isolation and biological properties. Samanta AK, Bose SK. J Antibiot (Tokyo). 1984 Jul;37(7):728-32.A new antifungal antibiotic, mycoversilin, was isolated from the culture filtrate of Aspergillus versicolor (N5)17 by repeated column chromatography and recrystallized from ethyl acetate as homogeneous fine needles. Maximum production took place in a medium containing 4% glucose and 1% peptone at pH 3.5, temperature 28 degrees C after 8-9 days of incubation under stationary condition. Mycoversilin is a narrow spectrum antibiotic with activity against filamentous fungi, particularly Trichophyton rubrum (MIC 15 micrograms/ml).
256Isolation, structures, and antifungal activities of new aureobasidins.Yoshikawa Y, Ikai K, Umeda Y, Ogawa A, Takesako K, Kato I, Naganawa H. J Antibiot (Tokyo). 1993 Sep;46(9):1347-54.Aureobasidins are a group of cyclic depsipeptides with antifungal activity and are produced by Aureobasidium pullulans. Aureobasidins are composed of eight amino acids and one hydroxy acid such as 2-hydroxy-3-methylpentanoic acid (Hmp), and highly lipophilic. Five new aureobasidins, S1, S2a, S2b, S3 and S4, which have higher hydrophilicity in reversed phase HPLC than the known aureobasidins A-R, were discovered in a fermentation broth of A. pullulans R106 by means of on-line liquid chromatography/mass spectrometry with electrospray ionization. We identified the structures of the compounds and studied their antifungal activities. Three of the new aureobasidins, S2b, S3 and S4, which have hydroxylated Hmp as the hydroxy acid, were highly active against Candida spp. and Cryptococcus neoformans.
257 Aureobasidins, new antifungal antibiotics. Taxonomy, fermentation, isolation, and properties. Takesako K, Ikai K, Haruna F, Endo M, Shimanaka K, Sono E, Nakamura T, Kato I, Yamaguchi H. J Antibiot (Tokyo). 1991 Sep;44(9):919-24.Aureobasidins A to R were isolated from the fermentation broth of Aureobasidium pullulans R106. Aureobasidins are cyclic depsipeptide antibiotics with MW's ranging from 1.070 to 1,148. Aureobasidins showed high in vitro antifungal activity against Candida albicans
258Unique molecular conformation of aureobasidin A, a highly amide N-methylated cyclic depsipeptide with potent antifungal activity: X-ray crystal structure and molecular modeling studies. In Y, Ishida T, Takesako K. J Pept Res. 1999 May;53(5):492-500.A structural feature of aureobasidins, cyclic depsipeptide antibiotics produced by Aureobasidium pullulans R106, is the N-methylation of four out of seven amide bonds. In order to investigate possible relationship between the molecular conformation and the amide N-methylation, aureobasidin A (AbA), which exhibits the potent antifungal activity, was subjected to X-ray crystal analysis. The crystal, recrystallized from ether (orthorhombic, space group P2(1)2(1)2(1), a = 21.643 (3) A, b = 49.865(10) A, c = 12.427 (1) A, z= 8), contained two independent conformers per asymmetric unit and they took on a similar arrowhead-like conformation. The conformation consisted of three secondary structures of antiparallel beta-sheet, and beta- and gamma-turns, and was stabilized by three intramolecular and transannular N-H O=C hydrogen bonds. The beta-hydroxy-N-methyl-l-valine residue, which is indispensable for its bioactivity, was located at the tip of the corner. Since a nearly identical conformation has been observed for aureobasidin E, a related cyclic depsipeptide, this arrowhead-like conformation may be energetically stable and important for biological activity. The contribution of the amide N-methylation to the conformation was investigated by model building and energy calculations. The energy-minimizations of AbA analogs, in which some (one to four) of four N-methylated amide bonds were replaced with usual amide bond, led to some conformers which are fairly different from the arrowhead form of AbA, although they are stabilized by three intramolecular N-H...O=C hydrogen bonds. This result explains the reason why four out of the seven amide bonds have to be methylated to manifest biological activity, i.e. the high N-methylation of aureobasidin is necessary to form only one well-defined conformation.
276Toxic properties of Beauveria pigments on erythrocyte membranes. Jeffs LB, Khachatourians GG. Toxicon. 1997 Aug;35(8):1351-6.The Beauveria pigments, tenellin, bassianin and oosporein, all inhibited total erythrocyte membrane ATPase activity in a dose-dependent manner by as much as 50% at 200 micrograms/ml. These pigments inhibited Ca(2+)-ATPases to a greater extent than Na+/K(+)-ATPase activity. The ATPase inhibitory activity for these pigments was not specific but was probably a consequence of membrane disruption, since pigments all caused alterations in erythrocyte morphology and promoted varying degrees of cell lysis.
287Bipolaroxin, a selective phytotoxin produced by Bipolaris cynodontis. Sugawara F, Strobel G, Fisher LE, Van Duyne GD, Clardy J. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8291-4.Two sesquiterpenes have been isolated from the fungal pathogen of Bermuda grass Bipolaris cynodontis. Chemical, spectral, and x-ray diffraction studies have led to the characterization of these as bipolaroxin and dihydrobipolaroxin, highly oxygenated members of the eremophilane family. Bipolaroxin is phytotoxic to some but not all of the plants tested. To our knowledge, a phytotoxin with host selectivity isolated from a weed pathogen has not been reported previously.
288A 13-kilodalton maize mitochondrial protein in E. coli confers sensitivity to Bipolaris maydis toxin. Dewey RE, Siedow JN, Timothy DH, Levings CS 3rd. Science. 1988 Jan 15;239(4837):293-5.The Texas male-sterile cytoplasm (cms-T) of maize carries the cytoplasmically inherited trait of male sterility. Mitochondria isolated from cms-T maize are specifically sensitive to a toxin (BmT-toxin) produced by the fungal pathogen Bipolaris maydis, race T, and the carbamate insecticide methomyl. A mitochondrial gene unique to cms-T maize, which produces a 13-kilodalton polypeptide associated with cytoplasmic male sterility, was expressed in Escherichia coli. After addition of BmT-toxin or methomyl, inhibition of whole cell respiration and swelling of spheroplasts were observed in Escherichia coli cultures producing the novel mitochondrial protein; these effects are similar to those observed with isolated cms-T mitochondria. The amino-terminal region of the 13-kilodalton polypeptide appears to be essential for proper interaction with the BmT-toxin and methomyl. These results implicate the 13-kilodalton polypeptide in conferring toxin sensitivity to mitochondria of cms-T maize.
289Mutations in the maize mitochondrial T-urf13 gene eliminate sensitivity to a fungal pathotoxin. Braun CJ, Siedow JN, Williams ME, Levings CS 3rd. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4435-9.URF13, the product of the mitochondrial T-urf13 gene, confers on Texas cytoplasmic male-steril maize (Zea mays L.) a unique susceptibility to a fungal pathogen (Bipolaris maydis race T) and sensitivity to its pathotoxin. Expression of URF13 in Escherichia coli imparts pathotoxin sensitivity to the bacterium. We show by ion uptake studies in E. coli that a pathotoxin-URF13 interaction causes membrane permeability. Similarly, mitochondrial dysfunction caused by membrane permeabilization probably accounts for increased colonization of maize carrying the Texas cytoplasm by toxin-producing pathogens. Site-directed mutagenesis studies show that approximately one-quarter of the amino acids at the carboxyl end of URF13 can be eliminated without affecting toxin sensitivity. We have identified two dicyclohexylcarbodiimide (DCCD) binding sites in the URF13 protein and show that one of the sites is involved in conferring DCCD protection against the pathotoxin. Substitutional mutations at this DCCD binding site also eliminate toxin sensitivity.
314 Toxicity of Blastomyces dermatitidis. Landay ME, Huang KY, Grogan TM. Mycopathol Mycol Appl. 1971 Oct 13;45(2):125-9. (No abstract available) 
345The antibiotic properties of the phytotoxic metabolites of Botrytis cinerea Pers.] Rubezhniak IG, Troshin LP, Zaĭchenko AM. Mikrobiol Z. 1995 Nov-Dec;57(6):46-51.Antibiotic properties of substances of a phytotoxic complex from Botrytis cinerea have been studied for a number of phytopathogenic bacteria, phytopathogenic and toxigenic fungi as well as saprophytic yeast strains. High fungistatic activity of preparations of phytotoxic metabolites (PTM) has been stated for Dendrodochium toxicum, Myrothecium verrucaria, M. roridum, Aspergillus fumigatus, Penicillium urticae, agents of heavy human and cattle mycotoxicoses. The studied representatives of phytopathogenic fusaria differed significantly in sensitivity to PTM: all the strains studied of the species from section Discolor (Fusarium gibbosum 54,624 and 51,463, F. graminearum 108,269, F. sambucinum 54,968, F. culmorum 54,951) were actively inhibited by the PTM concentrations studied; F. sporotrichiella 52,290 proved to be insensitive to them; the strains studied of the species from sections Elegans (F. oxysporum 55,715, F. moniliforme 54,262) and Martiella (F. javanicum 54,075, F. solani 54,719) possessed different sensitivity to PTM. The overwhelming majority of the yeast strains proved to be resistant to the PTM concentrations studied, except for the strains of Trichosporon cutaneum. In this connection the fact of high sensitivity of one of the strains of Kluyveromyces marxianus var. marxianus to B. cinerea metabolites arouses great interest. The strains of studied phytopathogenic bacteria (Erwinia carotovora subsp. carotovora 8,982 and Clavibacter michiganense 13) were sensitive to higher concentrations of PTM.
349Genetic modification of an echinocandin B-producing strain of Aspergillus nidulans to produce mutants blocked in sterigmatocystin biosynthesis. Hodges RL, Hodges DW, Goggans K, Xuei X, Skatrud P, McGilvray D. J Ind Microbiol. 1994 Nov;13(6):372-81.The production of echinocandin B (ECB), a lipopolypeptide used for chemical manufacture of the anti-Candida agent Cilofungin, was accomplished by fermentation using a strain of Aspergillus nidulans. In addition to ECB, this fermentation also produces a significant amount of sterigmatocystin (ST), a potent carcinogen structurally related to the aflatoxins. Mutants blocked in the ST biosynthetic pathway were created by genetic modification of the polyploid production strain C747. The following steps were involved: (i) reduction of the genotype to haploid by treatment with the spindle fiber poison methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate (MBC), using colony morphology, conidia size, and the ability to obtain 5-fluoro-orotic acid (5-FOA)-resistant mutants as criteria for ploidy; (ii) mutagenesis of a haploid isolate using UV irradiation; and (iii) screening of mutants for inability to produce ST by thin layer chromatography. Six mutants blocked in ST production were isolated. All six remained capable of producing ECB equivalent in quantity to the haploid strain C747-GR14. One of the mutants was shown to be the result of a chromosomal translocation.
350 "Canditoxin", a new toxic substance isolated from Candida albicans. 1. Relationship between strains and virulence, and conditions for the production of the toxic substance] Iwata K, Uchida K, Endo H. Igaku To Seibutsugaku. 1967 Jun 10;74(6):346-50. 
351  An examination of the production of hydrolytic enzymes and toxins by pathogenic strains of Candida albicans. Chattaway FW, Odds FC, Barlow AJ. J Gen Microbiol. 1971 Aug;67(3):255-63. 
352In situ mycotoxin production by Candida albicans in women with vaginitis. Shah DT, Glover DD, Larsen B. Gynecol Obstet Invest. 1995;39(1):67-9.The virulence attributes of Candida albicans in cases of mucocutaneous disease have not been identified. Based on the recent finding that C. albicans is able to produce an immunosuppressive mycotoxin, gliotoxin, we analyzed vaginal samples of 3 women severely symptomatic for vaginal candidiasis and found that they contained significant levels of gliotoxin. Three control women who were not colonized with C. albicans showed no gliotoxin in vaginal samples. These findings raise the possibility that gliotoxin may play a role in the virulence of C. albicans.
398Beticolins, nonpeptidic, polycyclic molecules produced by the phytopathogenic fungus Cercospora beticola, as a new family of ion channel-forming toxins. Goudet C, Milat ML, Sentenac H, Thibaud JB. Mol Plant Microbe Interact. 2000 Feb;13(2):203-9.Beticolins are toxins produced by Cercospora beticola, a phytopathogenic fungus responsible for the leaf spot disease of sugar beet. They form a family of 20 nonpeptidic compounds (named B0 to B19) that share the same polycyclic skeleton but differ by isomeric configuration (ortho- or para-) and by a variable residue R (bridging two carbons in one of the six cycles). It has been previously shown that B0 assembles itself into a multimeric structure and forms ion channels into planar lipid bilayers (C. Goudet, A.-A. Very, M.-L. Milat, M. Ildefonse, J.-B. Thibaud, H. Sentenac, and J.-P. Blein, Plant J. 14:359-364, 1998). In the present work, we investigate pore formation by three ortho-beticolins, B0, B2, and B4, and their related (i.e., same R) para-isomers, B13, B1, and B3, respectively, using planar lipid bilayers. All beticolins were able to form ion channels with multiple conductance states, although the type of cyclization (ortho- or para-) and residue (R) result in variations of channel conductance and ionic permeability, respectively. Channel formation by beticolins is likely to be involved in the biological activity of these toxins.
399Cercospora beticola Toxins (X. Inhibition of Plasma Membrane H+-ATPase by Beticolin-1). Simon-Plas F, Gomes E, Milat ML, Pugin A, Blein JP. Plant Physiol. 1996 Jul;111(3):773-779.Beticolin-1 is a toxin produced by the fungus Cercospora beticola. The chemical structure of this toxin was previously elucidated. The effects of beticolin-1 on purified corn root plasma membrane H+-ATPase were studied in a solubilized form or were reconstituted into liposome membranes. The ATP hydrolysis activity of the purified solubilized enzyme was inhibited by micromolar concentrations of beticolin-1, and this inhibition was noncompetitive with respect to ATP. When this purified enzyme was inserted into liposome membranes, a competitive inhibition of the H+-ATPase hydrolysis activity by beticolin-1 was observed. The effect of beticolin-1 on the formation of H+-ATPase-phosphorylated intermediate was also studied. With the purified enzyme in its solubilized form, the level of phosphorylated intermediate was not affected by the presence of beticolin-1, whereas micromolar concentrations of the toxin led to a marked inhibition of its formation when the enzyme was reconstituted into liposomes. These data suggest that (a) the plasma membrane H+-ATPase is a direct target for beticolin-1, and (b) the kinetics of inhibition and the effect on the phosphorylated intermediate are linked and both depend on the lipid environment of the enzyme.
400Cercospora beticola toxins. Part XVII. The role of the beticolin/Mg2+ complexes in their biological activity. Study of plasma membrane H(+)-ATPase, vacuolar H(+)-PPase, alkaline and acid phosphatases. Gomès E, Gordon-Weeks R, Simon-Plas F, Pugin A, Milat ML, Leigh RA, Blein JP. Biochim Biophys Acta. 1996 Nov 13;1285(1):38-46.Beticolin-1 and beticolin-2, yellow toxins produced by the phytopathogenic fungus Cercospora beticola, inhibit the plasma membrane H(+)-ATPase. Firstly, since beticolins are able to form complexes with Mg2+, the role of the beticolin/Mg2+ complexes in the inhibition of the plasma membrane proton pump has been investigated. Calculations indicate that beticolins could exist under several forms, in the H(+)-ATPase assay mixture, both free or complexed with Mg2+. However, the percentage inhibition of the H(+)-ATPase activity is correlated to the concentration of one single form of beticolin, the dimeric neutral complex Mg2H2B2, which appears to be the active form involved in the H(+)-ATPase inhibition. Secondly, since previous data suggested that beticolins could also be active against other Mg2(+)-dependent enzymes, we tested beticolin-1 on the vacuolar H(+)-PPase, which requires Mg2+ as co-substrate, and on the alkaline and acid phosphatases, which do not use Mg2+ as co-substrate. Only vacuolar H(+)-PPase is sensitive to beticolin-1, which suggests that beticolins are specific to enzymes that use a complex of Mg2+ as the substrate. The same Mg2H2B2 complex which is responsible of the plasma membrane H(+)-ATPase inhibition appears to be also involved in the inhibition of the vacuolar H(+)-PPase.
401Cercospora beticola toxins. VII. Fluorometric study of their interactions with biological membranes. Mikes V, Milat ML, Pugin A, Blein JP. Biochim Biophys Acta. 1994 Oct 12;1195(1):124-30.The interactions of two beticolins, Cercospora beticola toxins, and of their magnesium complexes with liposomes or plasma membrane were studied. The fluorometric pH titration curves of beticolins in liposomes and in plasma membranes reveal the presence of the dissociated form of beticolins. The concentration of the magnesium complex in these membranes increases at high pH. The partition coefficient of beticolin-1 on liposomes is 3-fold higher than that of beticolin-2 and the fluorescence of both compounds on liposomes is similar. The addition of magnesium to liposomes causes a 40-fold and 20-fold increase in the partition coefficient of beticolin-1 and -2, respectively, as a result of the interactions between membrane, magnesium and beticolins. Beticolins react to a delta pH across the liposome membrane but the formation of the magnesium complex completely abolishes this effect
402The Photoactivated Cercospora Toxin Cercosporin: Contributions to Plant Disease and Fundamental Biology. Daub ME, Ehrenshaft M. Annu Rev Phytopathol. 2000;38:461-490.Plant pathogenic fungi in eight genera produce light-activated perylenequinone toxins that are toxic to plants via the generation of activated oxygen species, particularly singlet oxygen. Studies on the cercosporin toxin produced by Cercospora species have documented an important role for this toxin in pathogenesis of host plants. Cercosporin-generated active oxygen species destroy the membranes of host plants, providing nutrients to support the growth of these intercellular pathogens. Resistance of Cercospora species to the toxic effects of their own toxin has allowed these organisms to be used as a model for understanding the cellular basis of resistance to singlet oxygen and to general oxidative stress. In particular, the recent discovery that pyridoxine (vitamin B6) quenches singlet oxygen has led to the understanding of a novel role for this vitamin in cells as well as the discovery of a novel pathway of biosynthesis.
403Differential response of maize catalases and superoxide dismutases to the photoactivated fungal toxin cercosporin. Williamson JD, Scandalios JG. Plant J. 1992 May;2(3):351-8.Many fungi of the genus Cercospora produce a light-induced, photoactivated polyketide toxin called cercosporin. In the presence of light an excited form (triplet state) of the toxin molecule is produced which, depending on the reducing potential of the environment, reacts with molecular oxygen to produce singlet oxygen and/or superoxide radicals. In this paper a system is presented for analysis of antioxidant defense gene response using purified cercosporin under conditions demonstrated to favor superoxide formation. Under the assay conditions employed, changes in total catalase activity, as well as individual isozyme protein levels generally mirrored the changes observed in corresponding steady-state RNA levels in response to applied cercosporin. In contrast, while transcript accumulation for most maize superoxide dismutases increased dramatically, both total superoxide dismutase activity and individual isozyme protein levels remained constant in all toxin treatments. In one case, the analyses indicated that there are two distinct transcripts that hybridize with a gene-specific probe for Sod3. These two transcripts responded differentially to applied toxin (levels of the larger transcript increased while the smaller decreased), whereas corresponding steady-state levels for the SOD-3 isozyme proteins remained constant. This suggests that protein turnover might play a role in the response of these SODs to activated oxygen species.
404Dothistromin as a metabolite of Cercospora arachidicola. Stoessl A. Mycopathologia. 1984 Jun 30;86(3):165-8.The known phytotoxin dothistromin has been newly identified as a metabolite of the peanut pathogen Cercospora arachidicola. The potential of the substance as a mycotoxin is discussed.
405Some biological properties of traversianal, a strongly molluscicidal diterpenoid aldehyde from Cercospora traversiana. Stoessl A, Cole RJ, Abramowski Z, Lester HH, Towers GH. Mycopathologia. 1989 Apr;106(1):41-6.The diterpenoid aldehyde traversianal, a metabolite of the fenugreek pathogen Cercospora traversiana, has been shown to be highly toxic to brine shrimp and snails, and to lyse human red blood cells at concentrations as low as 5 x 10(-7) M. The compound also induced betacyanin leakage from beetroot slices but was essentially inactive in other standard tests for phytotoxicity despite its structural similarities to known phytotoxins. It was inactive in the chick bioassay.
406Antimycobacterial Anthraquinone-Chromanone Compound and Diketopiperazine Alkaloid from the Fungus Chaetomium globosum KMITL-N0802. Kanokmedhakul S, Kanokmedhakul K, Phonkerd N, Soytong K, Kongsaeree P, Suksamrarn A. Planta Med. 2002 Sep;68(9):834-6. Investigation of the fungus Chaetomium globosum KMITL-N0802 led to the isolation of a novel anthraquinone-chromanone compound named chaetomanone along with seven known compounds, ergosterol, ergosteryl palmitate, chrysophanol, chaetoglobosin C, alternariol monomethyl ether, echinuline and isochaetoglobosin D. These compounds were characterized by spectroscopic methods. Chaetomanone and echinulin exhibited activity towards Mycobacterium tuberculosis.
407Chaetoatrosin A, a novel chitin synthase II inhibitor produced by Chaetomium atrobrunneum F449. Hwang EI, Yun BS, Kim YK, Kwon BM, Kim HG, Lee HB, Bae KS, Kim SU. J Antibiot (Tokyo). 2000 Mar;53(3):248-55.Chaetoatrosin A, a novel chitin synthase II inhibitor, was isolated from the culture broth of fungus F449, which was identified as Chaetomium atrobrunneum F449. Chaetoatrosin A was purified by solvent partition, silica gel, ODS, preparative TLC, and Sephadex LH-20 column chromatographies, consecutively. The structure of chaetoatrosin A was assigned as 1,8-dihydroxy-3(2-hydroxypropionyl)-6-methoxynaphthalene on the basis of various spectroscopic analyses including UV, IR, mass spectral, and NMR. Its molecular weight and formula were found to be 262 and C14H14O5, respectively. ,Chaetoatrosin A inhibited chitin synthase II by 50% at the concentration of 104 microg/ml in an enzyme assay system. This compound showed antifungal activities against Rhizoctonia solani, Pyricularia oryzae, Botrytis cinerea, Cryptococcus neoformans and Trichophyton mentagrophytes.
408 Chaetoglobosins, cytotoxic 10-(indol-3-yl)-[13]cytochalasans from Chaetomium spp. I. Production, isolation and some cytological effects of chaetoglobosins A-J. Sekita S, Yoshihira K, Natori S, Udagawa S, Sakabe F, Kurata H, Umeda M. Chem Pharm Bull (Tokyo). 1982 May;30(5):1609-17. 
409The production of chaetoglobosins, sterigmatocystin, O-methylsterigmatocystin, and chaetocin by Chaetomium spp. and related fungi. Udagawa S, Muroi T, Kurata H, Sekita S, Yoshihira K, Natori S, Umeda M.Can J Microbiol. 1979 Feb;25(2):170-7.Production of mycotoxins by Chaetomium spp. and related fungi on rice culture was examined by a combination of cytotoxicity tests using HeLa cells and thin-layer chromatography. Three species, C. mollipilium, C. rectum, and C. subaffine, as well as C. cochliodes and C. globosum, were proved to produce chaetoglobosins. From cultures of four strains of Chaetomium sp., assigned to C. thielavioideum, and one strain of Farrowia sp., chaetocin, sterigmatocystin, and O-methylsterigmatocystin were isolated. Morphological characteristics of the producers of sterigmatocystins are described.
410Biosynthesis of chaetochromin A, a bis(naphtho-gamma-pyrone), in Chaetomium spp. Koyama K, Natori S. Chem Pharm Bull (Tokyo). 1989 Aug;37(8):2022-5.The biosynthesis of chaetochromin A, a metabolite of Chaetomium gracile, has been studied using [13CH3]methionine, sodium [1-13C]acetate, sodium [1,2-13C2]acetate, sodium [1-13C,2,2,2-2H3]acetate, and sodium [1-13C,1,1-18O2]acetate as precursors. The folding pattern of the polyketide chain in chaetochromin A, biosynthesized from sodium [1,2-13C2]acetate as the precursor, was determined to be the same as that of rubrofusarin by carbon-13 nuclear magnetic resonance (13C-NMR) analysis. By using [13CH3]methionine as a precursor, the source of 2-CH3 was determined. When sodium [1-13C,2,2,2-2H3]acetate was fed, a beta-isotope-shifted peak was observed only for carbon 2. In the 13C-NMR spectra of chaetochromin A and of its hexamethyl ether derived from sodium [1-13C,1,1-18O2]acetate, isotope-shifted peaks were observed for carbons 4, 5, 6, 8 and 10a, but not for carbon 2. These results showed that oxygen 1 originated from the same unit of acetate as carbon 10a.
411 Chaetochromins B, C and D, bis(naphtho-gamma-pyrone) derivatives from Chaetomium gracile. Koyama K, Natori S. Chem Pharm Bull (Tokyo). 1987 Feb;35(2):578-84. 

Sporidesmins: XIII. Ovine III-thrift in Nova Scotia: III. The characterisation of chetomin a toxic metabolite of Chaetomium cochliodes and Chaetomium globosum. Safe S ; Taylor AJ Chem Soc Perkin Trans I; (4).1972 472-479

Chetomin, 1 of the antibiotic metabolites of Chaetomium cochliodes and C. globosum was isolated as an amorphous, glass-like solid. Elemental analysis of chetomin, its diacetate and its bistrimethylsilyl ether, mass spectroscopy of its tetrathiomethyl derivative, and NMR spectroscopy indicate the molecular formula to be C31H30N6O6S4. The formation of a tetra-S-methyl derivative and a bismonosulfide indicated the presence of 2 epidithiocioxopiperazine ring systems like those present in chaetocin, a metabolite of C. minutum, a conclusion supported by the close similarity of the c.d. (circular dichroism) of the 2 metabolites. The UV spectrum of chetomin was the same as that of echinulin. These facts, and an interpretation of the NMR spectra of chemotin and its derivatives indicate that the molecule contains an indole, an indoline and 2 epidithiodioxopiperazine systems. A biogenetically plausible assembly of these structural features is shown.
413 Sporidesmins. 8. Ovine ill-thrift in Nova Scotia. 3. The characterisation of chetomin a toxic metabolite of Chaetomium cochliodes and Chaetomium globosum. Safe S, Taylor A. J Chem Soc [Perkin 1]. 1972;4:472-9. 
414 Mycotoxin production by Chaetomium spp. and related fungi. Sekita S, Yoshihira K, Natori S, Udagawa S, Muroi T, Sugiyama Y, Kurata H, Umeda M. Can J Microbiol. 1981 Aug;27(8):766-72. 
415The antibacterial activity of some naturally occurring 2,5-dihydroxy-1,4-benzoquinones.
Brewer D, Jen WC, Jones GA, Taylor A. Can J Microbiol. 1984 Aug;30(8):1068-72.
Polyporic acid, atromentin, bovinone, and oosporein are common metabolic products of a number of species of fungi. The related compound cochliodinol and its congeners are produced by several Chaetomium spp. These quinonoid metabolites have been shown to inhibit the growth and metabolism of a range of bacterial genera. The antibiotic activity of the quinones depends on the substituents at the 3 and 6 positions of the 2,5-dihydroxy-1,4-benzoquinone ring; in aerobic systems the activity appears to be inversely proportional to the polarity of the metabolite. It has been shown that reduction of the quinone to the hydroquinone changes the antibiotic activity of these metabolites but does not abolish it. Contrary to previous reports, the activity of these hydroquinones is not reversed by cysteine.
416Mollicellins: mutagenic and antibacterial mycotoxins. Stark AA, Kobbe B, Matsuo D, Büchi G, Wogan GN, Demain AL. Appl Environ Microbiol. 1978 Sep;36(3):412-20.Eight mollicellins (depsidones) (from Chaetomium mollicellum) were assayed for mutagenicity and antibacterial activity in Salmonella/microsome tests involving histidine reversion and forward mutation to 8-azaguanine resistance. Two of them, mollicellins C and E, which contain a 3-methylbutenoic acid moiety, were mutagenic and bactericidal for Salmonella typhimurium in the absence of microsomes. Mollicellins D and F, each containing a chlorine atom, were bactericidal but not mutagenic. The mutagenic activity was completely abolished and the antibiotic activity was greatly reduced by coincubation with rat liver microsomes.
417Comparative toxicity of Chaetomium contaminated corn and various chemical forms of oosporein in broiler chicks. Manning RO, Wyatt RD. Poult Sci. 1984 Feb;63(2):251-9.The toxicity to broiler chicks of Chaetomium contaminated corn and various chemical forms of oosporein were compared by feeding diets containing 60% Chaetomium contaminated corn (300 micrograms oosporein/g diet), and 300 or 150 micrograms/g of purified oosporein in either the K salt, Na salt, or organic acid form from hatching to 3 weeks of age. The Chaetomium contaminated corn diet caused 100% mortality during the first week of feeding. Necropsies revealed extensive visceral and articular gout, enlarged pale kidneys, dehydration, proventricular enlargement with mucosal necrosis, and a dark green discoloration of the gizzard lining. When the mortality percentages of the two experiments conducted were considered collectively, the K and Na salts of oosporein caused significantly higher mortality than the organic acid form of oosporein. The K salt caused the most severe lesions and the organic acid caused the least severe lesions. No mortality occurred at the 150 micrograms/g K salt or 150 micrograms/g organic acid levels. Relative kidney weights were increased by all forms of oosporein at 300 micrograms/g, but at 150 micrograms/g only the K salt caused an increase in kidney weight. The LD50 values, based on mortality from 1 to 10 days, were 5.77, 5.00, and 4.56 mg/kg for oosporein acid, oosporein Na salt, and oosporein K salt, respectively. These results suggest that the salts of oosporein (particularly the K salt) are more toxic than the organic acid, and the natural occurrence of oosporein in a salt for. could contribute to the increased toxicity of the Chaetomium contaminated corn.
418Avian gout caused by oosporein, a mycotoxin produced by Chaetomium trilaterale. Pegram RA, Wyatt RD. Poult Sci. 1981 Nov;60(11):2429-40.In a series of four experiments, diets containing oosporein at graded concentrations from 0 to 600 microgram/g were fed to male broiler chicks from hatching to 3 weeks of age. At dietary toxin levels of 100 microgram/g and below, no detrimental effects were observed. Dietary oosporein concentrations of 200 microgram/g and above elicited dose-related mortality resulting from severe visceral and articular gout. Three-week cumulative mortality percentages were 0, 13, 30, 57, and 95% for the 0, 200, 300, 400, and 600 microgram/g levels, respectively. Upon necropsy, the prominent lesions observed were massive urate deposits in various tissues, swollen and pale kidneys, dehydration, proventricular enlargement with mucosal necrosis, and a green discoloration of the gizzard lining. The effects on the provent
riculus and gizzard occurred at doses as low as 200 microgram/g and were the most sensitive indicators of oosporein-toxicosis. In addition to the proventriculus, the relative weights of the kidney and liver were significantly increased in a dose-related fashion. A significant reduction in 3-week body weight at 400 microgram/g apparently resulted from the lower feed consumption concomitantly observed at this level of dietary toxin. Oosporein also caused an increase in water consumption at 400 and 600 microgram/g. Blood analyses indicated no toxin-related effect on plasma glucose, plasma protein, packed red blood cell volume, hemoglobin, and prothrombin times. The plasma concentration of uric acid was significantly elevated at 400 microgram/g. These data and mechanistic considerations suggest that oosporein should be classified as a nephrotoxin in the broiler chicken.
419 Toxic effects of oosporein from Chaetomium trilaterale. Cole RJ, Kirksey JW, Cutler HG, Davis EE. J Agric Food Chem. 1974 May-Jun;22(3):517-20. 
420Biosynthesis of mevinolin, a hypocholesterolemic fungal metabolite, in Aspergillus terreus.
Shiao MS, Don HS. Proc Natl Sci Counc Repub China B. 1987 Jul;11(3):223-31
Mevinolin and compactin are fungal metabolites which inhibit cholesterol biosynthesis in mammalian systems. Biogenetically, mevinolin is formed from polyketide chains, one 18-carbon and one 4-carbon, derived from acetate in normal head to tail fashion. The remaining two carbons in mevinolin, namely C-2' and C-6 methyl groups, are transferred from S-adenosylmethionine. To distinguish the timing and sequence of these two methylation steps, [Me-14C]- and [Me-3H,14C]-L-methionine were fed to Aspergillus terreus at several selected production intervals. Location and distribution of labels were determined by the specific chemical degradation methods. The results have demonstrated clearly that transfer of methyl groups from two S-adenosylmethionine molecules to the biosynthetic precursors of mevinolin was a sequential process. Methylation at C-6 preceded that at C-2' of mevinolin. Both methylation steps proceeded with complete retention of hydrogens. Methyl groups were probably transferred to the anion-like intermediates.
421Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs. Manzoni M, Rollini M. Appl Microbiol Biotechnol. 2002 Apr;58(5):555-64.Hypercholesterolemia is considered an important risk factor in coronary artery disease. Thus the possibility of controlling de novo synthesis of endogenous cholesterol, which is nearly two-thirds of total body cholesterol, represents an effective way of lowering plasma cholesterol levels. Statins, fungal secondary metabolites, selectively inhibit hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase, the first enzyme in cholesterol biosynthesis. The mechanism involved in controlling plasma cholesterol levels is the reversible inhibition of HMG-CoA reductase by statins, related to the structural similarity of the acid form of the statins to HMG-CoA, the natural substrate of the enzymatic reaction. Currently there are five statins in clinical use. Lovastatin and pravastatin (mevastatin derived) are natural statins of fungal origin, while symvastatin is a semi-synthetic lovastatin derivative. Atorvastatin and fluvastatin are fully synthetic statins, derived from mevalonate and pyridine, respectively. In addition to the principal natural statins, several related compounds, monacolins and dihydromonacolins, isolated fungal intermediate metabolites, have also been characterized. All natural statins possess a common polyketide portion, a hydroxy-hexahydro naphthalene ring system, to which different side chains are linked. The biosynthetic pathway involved in statin production, starting from acetate units linked to each other in head-to-tail fashion to form polyketide chains, has been elucidated by both early biogenetic investigations and recent advances in gene studies. Natural statins can be obtained from different genera and species of filamentous fungi. Lovastatin is mainly produced by Aspergillus terreus strains, and mevastatin by Penicillium citrinum. Pravastatin can be obtained by the biotransformation of mevastatin by Streptomyces carbophilus and simvastatin by a semi-synthetic process, involving the chemical modification of the lovastatin side chain. The hypocholesterolemic effect of statins lies in the reduction of the very low-density lipoproteins (VLDL) and LDL involved in the translocation of cholesterol, and in the increase in the high-density lipoproteins (HDL), with a subsequent reduction of the LDL- to HDL-cholesterol ratio, the best predictor of atherogenic risk. The use of statins can lead to a reduction in coronary events related to hypercholesterolemia, but the relationship between benefit and risk, and any possible interaction with other drugs, must be taken into account.
433Purification, characterization, and amino acid sequence of cerato-platanin, a new phytotoxic protein from Ceratocystis fimbriata f. sp. platani. Pazzagli L, Cappugi G, Manao G, Camici G, Santini A, Scala A. J Biol Chem. 1999 Aug 27;274(35):24959-64.A new phytotoxic protein (cerato-platanin) of about 12.4 kDa has been identified in culture filtrates of the Ascomycete Ceratocystis fimbriata f. sp. platani, the causal agent of canker stain disease. The toxicity of the pure protein was bioassayed by detecting the inducing necrosis in tobacco leaves. The pure protein also elicited host synthesis of fluorescent substances in tobacco and plane (Platanus acerifolia) leaves. We purified the protein from culture medium to homogeneity. Its complete amino acid sequence was determined; this protein consists of 120 amino acid residues, contains 4 cysteines (S-S-bridged), and has a high percentage of hydrophobic residues. The molecular weight calculated from the amino acid sequence agrees with that determined by mass spectrometry, suggesting that no post-transnational modification occurs. Searches performed by the BLAST program in data banks (Swiss-Prot, EBI, and GenBank(TM)) revealed that this protein is highly homologous with two proteins produced by other Ascomycete fungi. One, produced during infection of wheat leaves, is codified by the snodprot1 gene of Phaeosphaeria nodorum (the causal agent of glume blotch of wheat), whereas the other is the rAsp f13 allergen from Aspergillus fumigatus. Furthermore, the N terminus of cerato-platanin is homologous with that of cerato-ulmin, a phytotoxic protein belonging to the hydrophobin family and produced by Ophiostoma (Ceratocystis) ulmi, a fungus responsible for Dutch elm disease.
434Cerato-ulmin, a hydrophobin secreted by the causal agents of Dutch elm disease, is a parasitic fitness factor. Temple B, Horgen PA, Bernier L, Hintz WE. Fungal Genet Biol. 1997 Aug;22(1):39-53.Dutch elm disease is caused by the aggressive Ophiostoma novo-ulmi and the nonaggressive O. ulmi. Both secrete the protein cerato-ulmin (CU). To determine what role CU plays in the pathology of Dutch elm disease, we constructed a CU overexpression mutant of the nonaggressive O. ulmi H5. Stable integration of a single copy of the cu gene from the aggressive O. novo-ulmi into the genome of the nonaggressive isolate resulted in increased secretion of CU protein. Trials with American elm, Ulmus americana, suggested no alteration of virulence of this overexpressing transformant. Using aggressive and nonaggressive wild types, the cu overexpressing mutant, and our cu- mutant (Bowden et al., 1996), we have demonstrated that CU production is correlated with an altered phenotype and more hydrophobic and adherent yeast-like cells. Our results also demonstrate that CU has a role in protecting infectious propagules from desiccation. These biological roles for CU would affect transmission of Dutch elm disease, and we therefore propose that this hydrophobin acts as a parasitic fitness factor.
445TMC-69, a new antitumor antibiotic with Cdc25A inhibitory activity, produced by Chrysosporium sp. TC1068. Taxonomy, fermentation and biological activities.Hirano N, Kohno J, Tsunoda S, Nishio M, Kishi N, Okuda T, Kawano K, Komatsubara S, Nakanishi N. J Antibiot (Tokyo). 2001 May;54(5):421-7.Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, Saitama, Japan.
A new antibiotic designated TMC-69 has been isolated from the fermentation broth of a fungal strain Chrysosporium sp. TC 1068. TMC-69 exhibited moderate in vitro cytotoxic activity. TMC-69-6H, a derivative of TMC-69 prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma. TMC-69-6H was found to specifically inhibit Cdc25A and B phosphatases.
459Isocladosporin, a biologically active isomer of cladosporin from Cladosporium cladosporioides. Jacyno JM, Harwood JS, Cutler HG, Lee MK. J Nat Prod. 1993 Aug;56(8):1397-401.Extraction of the fungus Cladosporium cladosporioides yielded the known isocoumarin, cladosporin [1], and a new compound. This metabolite, which inhibited the growth of etiolated wheat coleoptiles slightly more than did cladosporin, was characterized as a diastereoisomer of cladosporin at C-14 and was named isocladosporin [2].

487A fatty acid synthase gene in Cochliobolus carbonum required for production of HC-toxin, cyclo(D-prolyl-L-alanyl-D-alanyl-L-2-amino-9, 10-epoxi-8-oxodecanoyl). Ahn JH, Walton JD.
Mol Plant Microbe Interact. 1997 Mar;10(2):207-14.

The fungal maize pathogen Cochliobolus carbonum produces a phytotoxic and cytostatic cyclic peptide, HC-toxin, of structure cyclo(D-prolyl-L-alanyl-D-alanyl-L-Aeo), in which Aeo stands for 2-amino-9,10-epoxi-8-oxodecanoic acid. Here we report the isolation of a gene, TOXC, that is present only in HC-toxin-producing (Tox2+) fungal strains. TOXC is present in most Tox2+ strains in three functional copies, all of which are on the same chromosome as the gene encoding HC-toxin synthetase. When all copies of TOXC are mutated by targeted gene disruption, the fungus grows and sporulates normally in vitro but no longer makes HC-toxin and is not pathogenic, indicating that TOXC has a specific role in HC-toxin production and hence virulence. The TOXC mRNA is 6.5 kb and the predicted product has 2,080 amino acids and a molecular weight of 233,000. The primary amino acid sequence is highly similar (45 to 47% identity) to the beta subunit of fatty acid synthase from several lower eukaryotes, and contains, in the same order as in other beta subunits, domains predicted to encode acetyl transferase, enoyl reductase, dehydratase, and malonyl-palmityl transferase. The most plausible function of TOXC is to contribute to the synthesis of the decanoic acid backbone of Aeo.
488Toxin-deficient mutants from a toxin-sensitive transformant of Cochliobolus heterostrophus. Yang G, Turgeon BG, Yoder OC. Genetics. 1994 Jul;137(3):751-7.Tox1 is the only genetic element identified which controls production of T-toxin, a linear polyketide involved in the virulence of Cochliobolus heterostrophus to its host plant, corn. Previous attempts to induce toxin-deficient (Tox-) mutants, using conventional mutagenesis and screening procedures, have been unsuccessful. As a strategy to enrich for Tox- mutants, we constructed a Tox1+ strain that carried the corn T-urf13 gene (which confers T-toxin sensitivity) fused to a fungal mitochondrial signal sequence; the fusion was under control of the inducible Aspergillus nidulans pelA promoter which, in both A. nidulans and C. heterostrophus, is repressed by glucose and induced by polygalacturonic acid (PGA). We expected that a transformant carrying this construction would be sensitive to its own toxin when the T-urf13 gene was expressed. Indeed, the strain grew normally on medium containing glucose but was inhibited on medium containing PGA. Conidia of this strain were treated with ethylmethanesulfonate and plated on PGA medium. Among 362 survivors, 9 were defective in T-toxin production. Authenticity of each mutant was established by the presence of the transformation vector, proper mating type, and a restriction fragment length polymorphism tightly linked to the Tox1+ locus. Progeny of each mutant crossed to a Tox1+ tester segregated 1:1 (for wild type toxin production vs. no or reduced toxin production), indicating a single gene mutation in each case. Progeny of each mutant crossed to a Tox1- tester segregated 1:1 (for no toxin production vs. no or reduced toxin production) indicating that each mutation mapped at the Tox1 locus. Availability of Tox- mutants will permit mapping in the Tox1 region without interference from a known Tox1 linked translocation breakpoint.
506Three new metabolites from marine-derived fungi of the genera coniothyrium and microsphaeropsis Holler U, Konig GM, Wright AD. J Nat Prod. 1999 Jan;62(1):114-8.The marine sponges Ectyplasia perox and Myxilla incrustans were investigated for associated fungal strains. Among others, a Coniothyrium sp., from E. perox, and a Microsphaeropsis sp., from M. incrustans, were isolated, cultured, and investigated for their biologically active secondary metabolite contents. The new compound microsphaeropsisin (1) together with the known compounds (R)-mellein (4), (3R,4S)-hydroxymellein (5), (3R,4R)-hydroxymellein (6), and 4, 8-dihydroxy-3,4-dihydro-2H-naphthalen-1-one (7) were isolated from the Microsphaeropsis sp. From culture extracts of the Coniothyrium sp., the new compounds (3S)-(3',5'-dihydroxyphenyl)butan-2-one (2) and 2-(1'(E)-propenyl)-octa-4(E),6(Z)-diene-1,2-diol (3), together with the six known metabolites (3R)-6-methoxymellein (8), (3R)-6-methoxy-7-chloromellein (9), cryptosporiopsinol (10), phenylethanol, (p-hydroxyphenyl)ethanol, and 2-(hydroxymethyl)furan, were obtained. All structures were determined using spectroscopic methods. With the exception of 3, all compounds were tested for their antimicrobial properties, and all but 10 demonstrated significant antimicrobial activity in agar diffusion assays.
513The green colour effect (GCE) of the killer strain Cryptococcus laurentii CBS 139 on Staib agar. Staib F. Mycoses. 1999 Apr;42(1-2):103-6.Attention is drawn to the observation that the type strain Cryptococcus laurentii CBS 139, producing killer toxins (mycocins) directed at Cr. neoformans var. gattii, causes a green colour effect (GCE) on Staib agar (Guizotia abyssinica creatinine agar) in combination with an intense assimilation of creatinine. Five (9.6%) out of 52 strains of Cr. laurentii of various origin, showed a GCE and intense creatinine assimilation. Further research must show if all Cr. laurentii strains, characterized by a GCE similar to that of the strain CBS 139, are also capable of producing killer toxins. For further ecological and epidemiological research on strains producing killer toxins directed against species of the genus Cryptococcus, it is proposed to use Staib agar as differential culture medium indicating both colour effects, i.e. the GCE and the brown colour effect (BCE).
514Microcin production by the yeast Cryptococcus humicola. Golubev W, Shabalin Y.
FEMS Microbiol Lett. 1994 Jun 1;119(1-2):105-10.
Cryptococcus humicola strains secrete killer toxins inhibitory (at pH values ranging from 3 to 5.5) to many ascomycetous and basidiomycetous yeast-like fungi. RNA or DNA plasmids were not detected in the killers. The amino acid-containing toxins were of low M(r), soluble in methanol, resistant to proteolysis, thermostable, cellophane-diffusible and were specified as microcins. These findings show that the killer phenomenon in yeasts such as bacteriocinogeny may be due to excretion of two types of killer toxins: mycocins and microcins.
515Production of antibacterial compounds by phylloplane-inhabiting yeasts and yeastlike fungi. McCormack PJ, Wildman HG, Jeffries P. Appl Environ Microbiol. 1994 Mar;60(3):927-31.The production of antibacterial compounds by yeasts and yeastlike fungi isolated from the phylloplane is reported. Aureobasidium pullulans, Citeromyces matritensis, Cryptococcus laurentii, Rhodotorula glutinis, and Sporobolomyces roseus produced antibacterial compounds inhibitory to both Pseudomonas fluorescens and Staphylococcus aureus in an overlay bioassay. In contrast, isolates of Candida albicans, Filobasidium uniguttulatum, Saccharomyces cerevisiae, Torulaspora delbruckii, Tremella foliacea, Trichosporon beigelii, and Trichosporon dulcitum obtained from soil or from culture collections did not produce inhibitory compounds when screened by the same procedure. The production of antibacterial compounds was examined in more detail, using several isolates of A. pullulans distinguished by cluster analysis on the basis of biochemical and physiological tests. They were found to produce a range of antibacterial compounds with different activities. Two distinct antibiotics were produced by an isolate of A. pullulans in liquid culture during both the logarithmic and the stationary phases of growth.
576Experimental pheohyphomycosis and mycotoxicosis by Curvularia lunata in albino rats.Rout N, Nanda BK, Gangopadhyaya S. Indian J Pathol Microbiol. 1989 Jan;32(1):1-6.A rice contaminating fungus 'Curvularia lunata' yields 'Curvularin', a potent mycotoxin. Experimental Pheohyphomycosis and Mycotoxicosis were observed in albino rats. Spore suspension produced localised lesion; with simultaneous steroid therapy produced lesion in distant organs. Mycotoxin, Curvularin, produced hepatic necrosis.
577Isolation, and biological properties of a new cell cycle inhibitor, curvularol, isolated from Curvularia sp. RK97-F166.Honda Y, Ueki M, Okada G, Onose R, Usami R, Horikoshi K, Osada H. J Antibiot (Tokyo). 2001 Jan;54(1):10-6.A new cell growth inhibitor, curvularol, was isolated from the fermentation broth of Curvularia sp. RK97-F166. Curvularol showed no antibacterial activity, and very weak antifungal activity. However, curvularol inhibited the cell cycle progression of normal rat kidney (NRK) cells in G1 phase at 150 ng/ml. Curvularol induced the morphological reversion of srcts-transformed NRK cells at 100 ng/ml, and inhibited protein synthesis same as cycloheximide.
602 New antibiotics from Cylindrocarpon sp. Matsumoto M, Minato H, Uotani N, Matsumoto K, Kondo E. J Antibiot (Tokyo). 1977 Aug;30(8):681-2. 
603Antitumor activity of L-asparaginase from Cylindrocarpon obtusisporum MB-10 and its effect on the immune system. Raha SK, Dey SK, Roy SK, Chaudhuri S, Chakrabarty SL. Biochem Int. 1990 Sep;21(6):1001-11.L-Asparaginase from Cylindrocarpon obtusisporum MB-10 inhibits the growth of Ascites Fibrosarcoma and Dalton's Lymphoma tumor cells in vivo and significantly increases the survival rate of tumor bearing mice. The enzyme-treated normal mice become more healthy and survive longer than their usual life span. The spleen size of normal animals treated with L-asparaginase become larger, and the number of their rosetting T-lymphocytes along with the capacity of SRBC constellation gets increased. The surface topography of splenic T-lymphocytes of enzyme-treated mice exhibits some extensions of different parts of the membrane with ruffling of surface and formation of innumerable blebs, foldings, microvilli, etc. The adherence of leukocytes of peritoneal exudate cells of these mice is also enhanced. All results suggest that C. obtusisporum MB-10 L-asparaginase is active against tumors and non-immunosuppressive, and it deserves to be an immunotherapeutic agent.
610 The ilicicolins, antibiotics from Cylindrocladium ilicicola. Hayakawa S, Minato H, Katagiri K. J Antibiot (Tokyo). 1971 Sep;24(9):653-4. 
611 Cylindrochlorin, a new antibiotic produced by Cylindrocladium. Kato A, Ando K, Tamura G, Arima K. J Antibiot (Tokyo). 1970 Mar;23(3):168-9. 
616Antimicrobial and antitumoral activities of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species. Guiraud P, Steiman R, Seigle-Murandi F, Bartoli MH. Pharmazie. 1994 Apr;49(4):279-81.Antifungal, antibacterial and antitumoral properties of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one were researched. This compound was isolated from culture medium of a new Drechslera species from the area of the Dead Sea. The product exhibited a large activity spectrum against microorganisms, with interesting IC 50 values close to those obtained with reference compounds (kanamycin and ketoconazole). Antitumoral potentiality was 10 to 58 times less important than with doxorubicin, however IC 50 obtained were below 4 micrograms/ml, which is the threshold value proposed by National Cancer Institute for preliminary screening of active molecules.
617Cochlioquinone A, an inhibitor of diacylglycerol kinase. Machida T, Higashi K, Ogawara H. J Antibiot (Tokyo). 1995 Oct;48(10):1076-80.The effects of cochlioquinone A, isolated from Drechslera sacchari, were studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki = 3.1 microM. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhibited neither protein kinase C, epidermal growth factor receptor-associated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A reduced the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 microM, and simultaneously augmented the phosphorylation of 80 kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80 kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 microgram/ml). These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.
618Triticone A: a novel bioactive lactam with potential as a molecular probe. Kenfield D, Strobel S, Sugawara F, Berglund D, Strobel G. Biochem Biophys Res Commun. 1988 Nov 30;157(1):174-82.Triticone A is one member of a family of novel compounds which are spirocyclic lactams produced by several plant pathogenic fungi including Drechslera tritici repentis on wheat. It undergoes racemization to form triticone B and when tested, the enantiomeric mixture causes chlorosis and necrosis on a wide range of plants. Fluorescein diacetate treated protoplasts in conjunction with various triticone treatments allowed for accurate quantitation of the biological activity of the toxin. Various physiological functions of the wheat cell are impaired including the Hill and CO2 fixation reactions in photosynthesis. In addition, triticone A inhibits enzymes that have SH functional groups as part of their active site, eg., the protease-ficin. Neither triticone C or D had any activity in the enzyme or protoplast assays. It is apparent that triticone A has some potential as a molecular probe in a variety of biological systems.
619Cytochalasin B: preparation, analysis in tissue extracts, and pharmacokinetics after intraperitoneal bolus administration in mice. Lipski KM, McQuiggan JD, Loucy KJ, Fondy TP. Anal Biochem. 1987 Mar;161(2):332-40.Cytochalasin B (CB) was prepared by methanol extraction of dehydrated mold (Drechslera dematioidea) matte, reverse-phase C18 silica gel batch adsorption, selective elution with 1:1 (v/v) hexane:tetrahydrofuran (THF), crystallization, preparative TLC, and recrystallization. Unit gravity silica gel normal phase chromatography afforded additional CB. Yield per liter of medium was 300 mg of CB greater than 95% pure by NMR, HPLC (60:40 hexane:THF, Lichrosorb Si60 silica gel, 230 nm), and TLC. CB added exogenously to mouse organs at 1 and 5 micrograms/organ was recovered 70 to 100% by methanol extraction, adsorption to C18 silica gel Sep-Pak cartridges, elution with ethyl acetate, and analysis by TLC and/or HPLC. Limiting sensitivity (micrograms/extract) was 0.5 TLC; 1.0 HPLC. Quantitative extraction was confirmed with 3H-labeled CB. CB ip in mice at 50 mg/kg (LD10) distributed rapidly into liver, renal fat, kidney, intestines, mesentery, pancreas, spleen, and blood cells and was cleared from all but liver within 24 h. CB was below detectable levels in thymus, lymph nodes, heart, brain, bone marrow, and lungs. Cytochalasin A is fixed to tissues and not extractable. This work affords a source of CB in quantities permitting in vivo study, provides methods for extraction and analysis, and reveals the pharmacokinetics of ip bolus CB.
624 Studies on fungal products. IX. Dethiosecoemestrin, a new metabolite related to emestrin, from Emericella striata. Seya H, Nozawa K, Udagawa S, Nakajima S, Kawai K. Chem Pharm Bull (Tokyo). 1986 Jun;34(6):2411-6. 
625Experimental acute poisoning in mice induced by emestrin, a new mycotoxin isolated from Emericella species. Terao K, Ito E, Kawai K, Nozawa K, Udagawa S. Mycopathologia. 1990 Nov;112(2):71-9.The effects of emestrin (EMS), a secondary metabolite of the Emericella species, on male ICR mice were examined. The intraperitoneal LD50 values of EMS were 17.7 and 13.0 mg/kg at 24 and 48 hr, respectively. The target organs of EMS were the heart, liver and thymus. In doses over 30 mg/kg the experimental animals died from cardiac failure shortly after the injections. Several survivors that were given EMS in doses under 20 mg/kg showed severe centrilobular necrosis in the liver at 24 hr. Marked degeneration of mitochondria was seen in electron micrographs of both cardiac muscle cells and hepatocytes. In the degenerated hepatocytes, prominent proliferation of RER, membrane-limited inclusions containing both ribosome-like granules and RER, and fenestrated lamella-like structures were observed. Massive necrosis of lymphocytes was always observed in the cortical layer of the thymus of the survivors within 24 hr, while bilateral adrenalectomized mice showed no discernible pathomorphological changes in the lymphoid tissues. Pretreatment of mice with diethyl maleate increased the incidence and severity of hepatic necrosis, whereas that with either cysteine or CoCl2 reduced the severity of centrilobular necrosis of the liver. Pretreatment with phenobarbital had no significant effect on EMS-induced hepatic lesions.
626Isolation of a new tremorgenic indoloditerpene, 1'-O-acetylpaxilline, from Emericella striata and distribution of paxilline in Emericella spp. Nozawa K, Horie Y, Udagawa S, Kawai K, Yamazaki M. Chem Pharm Bull (Tokyo). 1989 May;37(5):1387-9.The distribution of a tremorgenic mycotoxin, paxilline (1), was investigated in 19 species belonging to the genus Emericella. It was found that Emericella desertorum, E. foveolata, and E. striata produced paxilline (1). A new type of indoloditerpene, emindole DA (4), was also found in E. quadrilineata. A new tremorgenic indoloditerpene, 1'-O-acetylpaxilline (3), was isolated from the mycelium of E. striata. Its structure was established on the basis of spectroscopic investigations.
627Correlation between the regulation of sterigmatocystin biosynthesis and asexual and sexual sporulation in Emericella nidulans. Guzmán-de-Peña D, Aguirre J, Ruiz-Herrera J. Antonie Van Leeuwenhoek. 1998 Feb;73(2):199-205.We analyzed the regulation of sterigmatocystin biosynthesis in wild type and mutant strains of Emericella nidulans (= Aspergillus nidulans). A positive correlation between both asexual and sexual sporulation and synthesis of the mycotoxin was observed. Those conditions which favored sporulation stimulated sterigmatocystin formation, and vice versa. Both processes were stimulated by light in a veA+ genetic background. In contrast, they were inhibited by diaminobutanone, an inhibitor of ornithine decarboxylase. The effect of this inhibitor was partially reverted by putrescine addition. Partial supplementation of specific requirements to auxotrophic mutants allowed normal vegetative growth, but interfered with asexual sporulation and sterigmatocystin biosynthesis. Synthesis of the mycotoxin was neither affected in a brlA mutant or in developmental mutants blocked at later steps in sporulation. As in wild type strain, diaminobutanone inhibited sterigmatocystin biosynthesis and cleisthotecia formation in the brlA mutant, and its effect was reverted by addition of putrescine. The inhibitor also affected the transcription of brlA. Our results indicate that sporulation and the synthesis of sterigmatocystin are co-regulated at a step previous to the brlA execution point.
628A new sterigmatocystin-producing Emericella variant from agricultural desert soils. Klich M, Mendoza C, Mullaney E, Keller N, Bennett JW. Syst Appl Microbiol. 2001 Apr;24(1):131-8.An unusual, sterigmatocystin-producing taxon with characteristics of both Emericella nidulans (anamorph Aspergillus nidulans) and Emericella rugulosa (anamorph Aspergillus rugulovalvus, formerly A. rugulosus) was isolated repeatedly during a mycofloral survey of desert cotton field soils where aflatoxin is a chronic problem. Members of this taxon had ascospores with smooth convex walls like E. nidulans but grew slowly like E. rugulosa; moreover, they were similar to an industrial echinocandin B-producing strain which had been classified as "Aspergillus nidulans var. roseus." These new desert isolates were compared with "A. nidulans var. roseus" and representative wild-type isolates of E. nidulans and E. rugulosa using traditional morphological characters, secondary metabolite profiles of mycelial extracts, and Southern blot analysis of genomic DNA. The desert isolates and "A. nidulans var. roseus shared morphological, physiological and molecular characters with E. rugulosa. These isolates constitute a new non-rugulose variant of E. rugulosa.
629Structures of novel epipolythiodioxopiperazines, emethallicins B, C, and D, potent inhibitors of histamine release, from Emericella heterothallica. Kawahara N, Nozawa K, Yamazaki M, Nakajima S, Kawai K. Chem Pharm Bull (Tokyo). 1990 Jan;38(1):73-8.Novel compounds designated emethallicins B (1), C (2), and D (3), along with emethallicin A (4), were isolated from the mycelium of the heterothallic fungus, Emericella heterothallica (mating type a). The structures of emethallicins B (1), C (2), and D (3) were determined on the basis of spectroscopic and chemical investigations. Emethallicins B (1) and C (2) are epitetrathiodioxopiperazines, which have the same basic carbon skeleton as apoaranotin (19) and acetylaranotin (17), respectively, whereas emethallicin D (3) is an epitrithiodioxopiperazine derivative, which has the same carbon skeleton as apoaranotin (19). It is very interesting that a large amount of the disulfide, emethallicin A (4), was isolated from the strain of mating type A and that the corresponding tetrasulfide, emethallicin B (1), and trisulfide, emethallicin D (3), were isolated from the other mating type strain, along with a small amount of the disulfide (4). Emethallicins B (1), C (2), and D (3) have potent inhibitory activity against compound 48/80-induced histamine release from mast cells, like emethallicin A (4).
630Structure of a novel epidithiodioxopiperazine, emethallicin A, a potent inhibitor of histamine release from Emericella heterothallica. Kawahara N, Nakajima S, Yamazaki M, Kawai K. Chem Pharm Bull (Tokyo). 1989 Oct;37(10):2592-5.A new epidithiodioxopiperazine derivative, emethallicin A (1), was isolated along with ergosterol from the mycelial extract of the heterothallic fungus, Emericella heterothallica (mating type A). The structure of emethallicin A (1) was established on the basis of chemical and spectroscopic investigations and finally by chemical transformation to apoaranotin (11). Emethallicin A (1) has the same basic skeleton as apoaranotin (11), with C6-C2 carboxylic acid (mandelic and phenylacetic acids) diester moieties, and showed a potent inhibitory activity on histamine release from mast cells.
631Antitumor efficacy in vitro and in vivo of falconensones, a new type of polyene. Tamagawa K, Shimizu K, Ebine T, Maitani Y, Fukui T, Kawai KI, Takahashi N. Clin Cancer Res. 2001 Nov;7(11):3551-8.Falconensones A and B are new type of yellow pigment isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis. To date, these falconensones and their derivatives, falconensone A p-bromophenylhydrazone and falconensone A dioxime are known to exhibit biological activities, which include growth inhibition and both induction of differentiation and apoptosis of HL60 human leukemia cells. The synthetic derivatives have been shown to be more potent than natural falconensone A and B in eliciting these activities. Herein, we investigate whether falconensones inhibit growth of other cancer cell lines in vitro, and we evaluate their ability to modify survival in C57 BL/6J mice using M5076 murine reticulosarcoma in vivo, which is established as the metastasis model. Falconensone A, falconensone A p-bromophenylhydrazone, and falconensone A dioxime inhibit growth of human myeloid leukemia cell lines, HL60 and HL60R, human hepatoma cell line HepG2, human prostate cancer cell line DU-145, and human breast cancer cell line MCF-7/Adr(R), whereas falconensone B, the 4'-nor-methyl derivative of falconensone A, shows extremely low or no activity. In contrast, all of the falconensones are active in growth inhibition of human breast cancer cell line MCF-7. Survival time of M5076-implanted mice was prolonged by treatment with falconensones, particularly falconensone A dioxime. These results indicate that falconensone A and its derivatives exhibit anticancer efficacy in a broad spectrum of cancer cell lines. These agents may have great potential for clinical use in the treatment of various cancers.
632Induction of apoptosis in the human promyelocytic leukemia cell line HL60 by falconensone A and its derivatives, new polyenes. Takahashi N, Kubo Y, Iwahori A, Kawai KI, Fukui T. Biol Pharm Bull. 2000 Jun;23(6):748-54.Falconensones A and B are a new type of yellow pigment with structural similarity to retinoic acid isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa. In the present study we show that falconensone A alone induced apoptosis of HL60 human leukemia cells, while falconensone B, the 4'-nor-methyl derivative of falconensone A, had much lower activity. The synthetic derivatives of falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime, were more potent than natural falconensone A and B as far as the induction of apoptosis was concerned. The induction of apoptosis by the falconensones correlated with their inhibition of cell growth. In addition, falconensones A and B, and falconensone A dioxime, increased the generation of intracellular reactive oxygen species, while falconensone A p-bromophenylhydrazone was inactive. These results suggest that falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime are potential new apoptosis-inducing agents. The enhanced generation of reactive oxygen species in cells may be involved in apoptosis induced by falconensone A and falconensone A dioxime, but not by falconensone A p-bromophenylhydrazone. It is also suggested that the methyl residue at the 4' position of the falconensone A cyclopentenone ring may be essential for the induction of apoptosis. Based on these results, falconensone A and its derivatives may be clinically useful in the treatment of some leukemias.
633Unguisin C, a GABA-containing cyclic peptide from the fungus Emericella unguis. Malmstrøm J, Ryager A, Anthoni U, Nielsen PH. Phytochemistry. 2002 Aug;60(8):869-72.Besides the known unguisins A and B, a new cyclic heptapeptide, unguisin C, containing a GABA-derived moiety in the ring, was isolated from the fungus Emericella unguis. The structure was determined by 1D and 2D NMR techniques. Marfey's method was used to determine the absolute stereochemistry. Precursor-directed biosynthesis of the unguisins was performed by supplementation of the culture medium with amino acids (L-Ala, L-Ser, L-Phe and L-Leu). A related cyclic heptapeptide, unguisin D, was detected by HPLC and characterized by sequence analysis using LC-QITMS.
634Unguisins A and B: new cyclic peptides from the marine-derived fungus emericella unguis Malmstrom J. J Nat Prod. 1999 May;62(5):787-9.Unguisin A (1) and B (2), the first cyclic heptapeptides containing GABA in the ring, were isolated from a marine-derived strain of Emericella unguis. The chemical structures of 1 and 2 were elucidated by extensive 2D NMR techniques, and the stereochemistry of the individual amino acids was determined using Marfey's method
635Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor. Malmstrøm J, Christophersen C, Barrero AF, Oltra JE, Justicia J, Rosales A. J Nat Prod. 2002 Mar;65(3):364-7.From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified. The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations. In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines. Varixanthone (4) showed antimicrobial activity.
662 New antibiotics from the fungus Epicoccum nigrum. I. Fermentation, isolation and antibacterial properties. Baute MA, Deffieux G, Baute R, Neveu A. J Antibiot (Tokyo). 1978 Nov;31(11):1099-101.An atmosphere isolate of the fungus Epicoccum nigrum was found to exhibit an activity against Staphylococcus aureus. A more active, non-sporulating variant of this strain was selected. From its fermentation broth, two novel compounds, epicorazines A and B, were isolated by preparative TLC and tested against a series of bacteria.
663 New antibiotics from the fungus Epicoccum nigrum. II. Epicorazine A: structure elucidation and absolute configuration. Deffieux G, Baute MA, Baute R, Filleau MJ. J Antibiot (Tokyo). 1978 Nov;31(11):1102-5.An antibiotic, epicorazine A, isolated from a particular strain of the fungus Epicoccum nigrum, was shown to be a new epidithiodiketopiperazine from its UV, IR, mass, NMR and CD spectra. X-Ray diffraction measures confirmed this structure and its absolute configuration.
664 New antibiotics from the fungus Epicoccum nigrum. III. Epicorazine B: structure elucidation and absolute configuration. Deffieux G, Filleau MJ, Baute R. J Antibiot (Tokyo). 1978 Nov;31(11):1106-9.Comparison of UV, IR, PMR and CD spectra of epicorazine B with those of epicorazine A, a previously isolated metabolite of Epicoccum nigrum, showed that they were isomers with the same epidithiodiketopiperazine skeleton. X-Ray determination of epicorazine B indicated that the difference is related to a cis-trans configuration.
665Comparison between antifungal and antibacterial activities of several strains of Epicoccum purpurascens from the Mediterranean area. Mallea M, Pesando D, Bernard P, Khoulalene B. Mycopathologia. 1991 Aug;115(2):83-8.The antimicrobial activities of seven Epicoccum purpurascens strains isolated either from evergreen oak leaves (Quercus ilex) collected over a period of one year, or from the atmosphere were compared in vitro. Two strains sporulated and conspicuously inhibited the growth of Staphylococcus aureus and Trichophyton mentagrophytes. Thin-layer chromatographic studies showed the existence of some compounds, such as flavipin, which were common to all the strains. Epicorazine B was present in the extracts of only the two most active strains
681Aflavinines and other antiinsectan metabolites from the ascostromata of Eupenicillium crustaceum and related species. Wang HJ, Gloer JB, Wicklow DT, Dowd PF. Appl Environ Microbiol. 1995 Dec;61(12):4429-35.This report describes the distribution of antiinsectan metabolites present in sclerotioid ascostromata produced by representative strains of Eupenicillium crustaceum and fungal taxa that are considered to be closely related. The hexane and chloroform extracts of E. crustaceum NRRL 3332 displayed significant antiinsectan activity in assays against the corn earworm, Helicoverpa zea. The major metabolite accounting for this antiinsectan activity was a known aflavinine analog, 10,23-dihydro-24,25-dehydroaflavinine, occurring at approximately 2.8 mg/g of dry ascostromata. In dietary assays at ca. 3,000 ppm, a 79% reduction in weight gain and a 42% reduction in feeding rate were observed in H. zea and Carpophilus hemipterus larvae, respectively. A new aflavinine analog, 10,23,24,25-tetrahydro-24-hydroxyaflavinine, was also identified. These aflavinine compounds are the first to be reported from a fungal genus other than Aspergillus. New macrophorin-type metabolites accounted for the antiinsectan activity of ascostromata produced by E. crustaceum NRRL 22307, which produced no aflavinines, while Eupenicillium molle NRRL 13062 produced both aflavinines and macrophorins. Sclerotia produced by Penicillium gladioli NRRL 938, NRRL 939, and QM 2743, a fungus reported to be conspecific with the anamorph of E. crustaceum, produced neither aflavinines nor macrophorins. Eupenicillium reticulisporum NRRL 3446 produced the aflavinine analog 10,23-dihydro-24,25-dehydroaflavinine and an unrelated compound called pyripyropene A, a potent inhibitor of acyl-coenzyme A-cholesterol acyltransferase. Eupenicillium abidjanum NRRL 5809, reported to be conspecific with E. reticulisporum, produced neither of these compounds. The Eupenicillium species that produced aflavinines are also known for their ability to grow rapidly with reduced water activity.
682. Immunosuppressive effect of bredinin on cell-mediated and humoral immune reactions in experimental animals. Kamata K, Okubo M, Ishigamori E, Masaki Y, Uchida H, Watanabe K, Kashiwagi N. Transplantation. 1983 Feb;35(2):144-9.Bredinin (BR), an imidazole nucleoside isolated from Eupenicillium brefeldianum was previously reported to prolong kidney allograft survival in dogs. The immunosuppressive effect of BR was studied in experimental animals. In beagles, in vitro responses of lymphocytes stimulated by mitogens or allogeneic cells were suppressed by in vitro BR treatment. BR, given in vivo, also showed an inhibitory action against development of delayed hypersensitivity reaction to tubercle bacilli in guinea pigs or against hemagglutinin production following booster SRBC injection in rabbits. Of note may be the fact that BR was found to have an immunosuppressive potency comparable to that of azathioprine and, in addition, to show a decreased hepatotoxicity compared with the latter.
683Production of brefeldin-A. McCloud TG, Burns MP, Majadly FD, Muschik GM, Miller DA, Poole KK, Roach JM, Ross JT, Lebherz WB 3rd. J Ind Microbiol. 1995 Jul;15(1):5-9.Fermentation conditions are described for the production of the antitumor antibiotic 7-(S)-brefeldin-A (brefeldin-A) in liquid culture by Eupenicillium brefeldianum, (B.Dodge) Stolk and Scott, ATCC 58665. An analytical hplc method was developed which allowed rapid quantitation of the compound during fermentation. A kilogram of brefeldin-A was isolated from a fermentation at the 6800-liter scale.
684Eupenifeldin, a novel cytotoxic bistropolone from Eupenicillium brefeldianum. Mayerl F, Gao Q, Huang S, Klohr SE, Matson JA, Gustavson DR, Pirnik DM, Berry RL, Fairchild C, Rose WC. J Antibiot (Tokyo). 1993 Jul;46(7):1082-8.Eupenifeldin was isolated from cultures of Eupenicillium brefeldianum ATCC 74184 by extraction and crystallization. The compound was identified as a pentacyclic bistropolone on the basis of spectral data and its complete structure was established by single-crystal X-ray analysis. The compound is cytotoxic against the HCT-116 cell line and has in vivo antitumor activity in the P388 leukemia model.
685Mizoribine and mycophenolate mofetil. Ishikawa H. Curr Med Chem. 1999 Jul;6(7):575-97.Both mizoribine (MZR) and mycophenolate mofetil (MMF) are immunosuppressive agents that inhibit the proliferation of lymphocytes selectively, via inhibition of IMPDH. MZR is a nucleoside of the imidazole class, isolated from the culture medium of the mold Eupenicillium brefeldianum M-2166. Although this compound has been found to have weak antimicrobial activity against Candida albicans, it has proved ineffective against experimental candidiasis. Unlike azathioprine, this compound is not taken up by nucleic acids in the cell. Instead, after phosphorylation MZR-5 -monophosphate inhibits GMP synthesis by the antagonistic blocking of IMPDH (Ki = 10(-8)M) and GMP- synthetase (Ki =10(-5) M). The drug has been found to inhibit both humoral and cellular immunity, and on this basis it was developed in Japan as an immunosuppressant. MZR has been shown in animal experiments to lack oncogenicity, and has been shown clinically to be associated with a low incidence of severe adverse reactions. MZR has been registered in Japan for the prevention of rejection in renal transplantation, and for the treatment of lupus nephritis, rheumatoid arthritis and the nephrotic syndrome. MMF is the morpholinoethyl ester prodrug of mycophenolic acid (MPA), which was first isolated in 1896 from the culture media of several Penicillium species. MPA has been evaluated for its unique properties as an anticancer, antiviral, antifungal and antibacterial agent, as well as for its therapeutic use in psoriasis and rheumatoid arthritis. MMF was designed to enhance the oral bioavailability of the parent compound. After beneficial effects were observed in animals, the clinical efficacy of MMF as an immunosuppressant in renal transplantation was studied in the United States. In 1995 the US Food and Drug Administration (FDA) approved the use of MMF for the prevention of rejection in renal transplantation, the drug also available on a number of European markets.
686Mollenines A and B: new dioxomorpholines from the ascostromata of Eupenicillium molle. Wang H, Gloer JB, Wicklow DT, Dowd PF. J Nat Prod. 1998 Jun 26;61(6):804-7.Two new dioxomorpholines (1 and 2) have been isolated from the sclerotioid ascostromata of Eupenicillium molle (NRRL 13062). Their structures were determined by analysis of NMR data. Mollenine A (1) exhibited moderate cytotoxicity and antibacterial activity, but neither compound displayed significant antiinsectan activity.
687Mycotoxin producing potential of some isolates of Aspergillus flavus and Eurotium groups from meat products. el-Kady I, el-Maraghy S, Zohri AN. Microbiol Res. 1994 Sep;149(3):297-307.All strains (92) of A. flavus group proved to be positive for production of aflatoxin (45 to 1200 micrograms/50 ml medium) on potato dextrose liquid medium, while 59 strains only proved to be positive (35-310 micrograms/50 ml) on 15% NaCl potato-dextrose liquid medium. Most of the strains tested of A. flavus, A. flavus var. columnaris and A. oryzae produced aflatoxins B1, B2, G1 & G2. All positive strains of A. tamarii produced aflatoxins G1 & G2 while the tested isolate of A. zonatus produced aflatoxins B1 & G1. Of 95 strains tested of Eurotium, aflatoxins B1 & G1 were produced by one strain of each of E. chevalieri var. intermedium, E. repens and E. rubrum. Gliotoxin was detected in the extract of two strains of E. chevalieri and one strain of each of E. chevalieri var. intermedium and E. pseudoglaucum on the salt-free medium, and two strains of each of E. chevalieri, E. chevalieri var. intermedium and one of E. pseudoglaucum on 15% NaCl medium. Sterigmatocystin was produced by some strains of E. chevalieri, E. chevalieri var. intermedium, E. amstelodami, E. pseudoglaucum and E. rubrum on the two experimental media. One strain only of E. repens produced ochratoxin A while citrinin was detected in the extract of one strain of E. pseudoglaucum.
688Metabolic products of microorganisms. 170. On the antibiotic activity of cladosporin. Anke H, Zähner H. Arch Microbiol. 1978 Mar;116(3):253-7.Cladosporin was isolated from the cultures of three species of the genus Eurotium. Cladosporin inhibited the growth of several fungi and at very low concentrations the growth of Bacillus brevis and Clostridium pasteurianum. Bacillus subtilis and most other Gram-positive bacteria were not sensitive. Gram-negative bacteria and yeasts were not affected by concentrations up to 100 microgram/ml. Dimethyl cladosporin showed only week activity against Bacillus brevis with the minimal inhibitory concentrations being a 100 times higher than of cladosporin. The incorporation of leucine and uracil into acid insoluble material in Bacillus brevis cells was completely inhibited by concentration of 0.5 microgram/ml cladosporin. The incorporation of thymidine was not affected at this concentration.
689Exophilin A, a new antibiotic from a marine microorganism Exophiala pisciphila. Doshida J, Hasegawa H, Onuki H, Shimidzu N. J Antibiot (Tokyo). 1996 Nov;49(11):1105-9.Exophilin A, a new antibacterial compound, was discovered in the culture of the marine microorganism Exophiala pisciphila NI10102, which was isolated from a marine sponge Mycale adhaerens. The absolute chemical structure of exophilin A was elucidated as a trimer of (3R,5R)-3,5-dihydroxydecanoic acid by spectroscopic methods and analyses of a degradative product. Exophilin A showed antimicrobial activity against Gram-positive bacteria.
740Antibiotic Y: biosynthesis by Fusarium avenaceum (Corda ex Fries) Sacc., isolation, and some physicochemical and biological properties. Goliński P, Wnuk S, Chełkowski J, Visconti A, Schollenberger M. Appl Environ Microbiol. 1986 Apr;51(4):743-5.A compound very similar to the mycotoxin citrinin was observed on thin-layer chromatographic plates during the screening analysis of grain extracts. This compound was produced by 22 of the tested Fusarium avenaceum (Corda ex Fries) Sacc. strains isolated from wheat, triticale, barley, corn, and potatoes. A chemical test confirmed the presence of an unknown compound, which was given the preliminary name of antibiotic Y (indicating yellow fluorescence). The following properties of the new metabolite are described: spectroscopic (UV, infrared, proton nuclear magnetic resonance, fluorescence, and mass spectrometry), phytotoxic, antibiotic (inhibitory effect of bacterial growth), and toxic (toxicity to Artemia salina, chicken embryos, and mouse fibroblasts). Elemental analysis of the compound showed that it had the general formula C15H10O8, in agreement with the mass spectrometric finding that the molecular ion had a molecular weight of 318. The structure of the compound is presently under study.
741Production of beauvericin, moniliformin, fusaproliferin, and fumonisins b(1), b(2), and b(3) by fifteen ex-type strains of fusarium species. Fotso J, Leslie JF, Smith JS. Appl Environ Microbiol. 2002 Oct;68(10):5195-7.Fifteen Fusarium species were analyzed by high-performance liquid chromatography for the production of six mycotoxins in corn grits cultures. Production of mycotoxins ranged from 66 to 2,500 micro g/kg for fumonisin B(1), 0.6 to 1,500 micro g/g for moniliformin, 2.2 to 720 micro g/g for beauvericin, and 12 to 130 micro g/g for fusaproliferin. Fumonisin B(2) (360 micro g/kg) was produced by two species, fumonisin B(3) was not detected in any of the 15 species examined, and Fusarium bulbicola produced none of the six mycotoxins that we analyzed.
742Occurrence of beauvericin and enniatins in wheat affected by Fusarium avenaceum head blight. Logrieco A, Rizzo A, Ferracane R, Ritieni A. Appl Environ Microbiol. 2002 Jan;68(1):82-5.We evaluated Fusarium contamination and the levels of hexadepsipeptide mycotoxins in 13 wheat samples affected by head blight in Finland. Fusarium avenaceum was the dominant species (91%) isolated from all samples, but isolates of F. culmorum (4%), F. tricinctum (3%), and F. poae (2%) also were recovered. Beauvericin (0.64 to 3.5 microg/g) was detected in all 13 samples. Enniatin B (trace to 4.8 microg/g) was detected in 12 samples, enniatin B(1) (trace to 1.9 microg/g) was detected in 8 samples, and enniatin A(1) (trace to 6.9 microg/g) was detected in 10 samples. Ten of 13 strains of F. avenaceum and 2 strains of F. poae and F. tricinctum produced beauvericin in culture on rice (trace to 70, 9.4, and 33 microg/g, respectively). All strains also produced enniatins (trace to 2,700 microg/g). This is the first report on the natural co-occurence of beauvericin and enniatins in wheat infected predominantly by F. avenaceum.
743Production of the mycotoxins fusaproliferin and beauvericin by South African isolates in the Fusarium section Liseola. Shephard GS, Sewram V, Nieuwoudt TW, Marasas WF, Ritieni A. J Agric Food Chem. 1999 Dec;47(12):5111-5.The production of fusaproliferin (FUS), a recently described mycotoxin, and beauvericin (BEA), a mycotoxin recently reported to co-occur with FUS in Fusarium-infected corn, by South African isolates in the Fusarium section Liseola, was investigated. Five isolates each of F. verticillioides, F. proliferatum, F. subglutinans, and F. globosum were cultured on corn kernels. Four each of the five South African isolates of F. proliferatum and F. subglutinans produced FUS (10-1725 and 330-2630 mg/kg, respectively). BEA was produced by four of the F. proliferatum strains (310-1130 mg/kg) and three of the F. subglutinans strains (140-700 mg/kg). The isolates of F. verticillioides failed to produce significant levels of either of these secondary metabolites. F. globosum was a weak producer of both in that one isolate of five produced 25 mg/kg FUS and five out of five produced BEA at levels ranging between 10 and 110 mg/kg. To further characterize these strains, their production of fumonisins B(1), B(2), and B(3), as well as moniliformin, was investigated. Of the four species investigated, fumonisins were produced by all except F. subglutinans, which in turn was the only species whose isolates in this study produced moniliformin (four of five isolates, ranging from 155 to 2095 mg/kg). Analysis of visibly Fusarium-infected home-grown corn collected in the Transkei region of the Eastern Cape Province of South Africa showed that nine of the ten samples contained low levels of FUS (up to 62 microg/kg), whereas all ten samples showed BEA contamination ranging from 8 to 1734 microg/kg with a mean of 258 microg/kg.
744Beauvericin production by Fusarium species. Logrieco A, Moretti A, Castella G, Kostecki M, Golinski P, Ritieni A, Chelkowski J. Appl Environ Microbiol. 1998 Aug;64(8):3084-8.Beauvericin is a cyclohexadepsipeptide mycotoxin which has insecticidal properties and which can induce apoptosis in mammalian cells. Beauvericin is produced by some entomo- and phytopathogenic Fusarium species (Fusarium proliferatum, F. semitectum, and F. subglutinans) and occurs naturally on corn and corn-based foods and feeds infected by Fusarium spp. We tested 94 Fusarium isolates belonging to 25 taxa, 21 in 6 of the 12 sections of the Fusarium genus and 4 that have been described recently, for the ability to produce beauvericin. Beauvericin was produced by the following species (with the number of toxigenic strains compared with the number of tested strains given in parentheses): Fusarium acuminatum var. acuminatum (1 of 4), Fusarium acuminatum var. armeniacum (1 of 3), F. anthophilum (1 of 2), F. avenaceum (1 of 6), F. beomiforme (1 of 1), F. dlamini (2 of 2), F. equiseti (2 of 3), F. longipes (1 of 2), F. nygamai (2 of 2), F. oxysporum (4 of 7), F. poae (4 of 4), F. sambucinum (12 of 14), and F. subglutinans (3 of 3). These results indicate that beauvericin is produced by many species in the genus Fusarium and that it may be a contaminant of cereals other than maize.
745Dermal toxicity of Fusarium toxins in combinations. Bhavanishankar TN, Ramesh HP, Shantha T. Arch Toxicol. 1988 Jan;61(3):241-4.T 2 toxin (T 2), diacetoxyscirpenol (DAS), fusarenon X (FX) and butenolide (Bd) at concentrations of 0.2, 0.3, 5 and 10 micrograms/site, respectively, were applied individually and in combinations on shaved skin of guinea pigs. Erythema and induration were observed on skin patches treated with the toxins. Increase in the thickness of stratum malpighii was the major histological change observed. Mild to moderate degeneration of fibrocytes and cellular infiltration were found in the corium of skin treated with FX, Bd, DAS and T 2. The order of toxicity of individual toxins was T 2 greater than DAS greater than FX greater than Bd. Combinations of T 2 + FX and T 2 + Bd resulted in antagonism, while DAS + FX and DAS + Bd caused synergism.
74613C NMR study of the biosynthesis of toxins by Fusarium graminearum. Blackwell BA, Miller JD, Greenhalgh R. J Biol Chem. 1985 Apr 10;260(7):4243-7.13C NMR spectroscopic investigations on the biosynthesis of mycotoxins produced by Fusarium graminearum (M69) were carried out through the incorporation of [1-13C]- and [2-13C]acetate precursors. The major secondary metabolites produced by this species in still culture were deoxynivalenol (3,7,15-trihydroxy-12,13-epoxytrichothec-9-en-one), 15-acetyldeoxynivalenol, zearalenone, and butenolide. [1-13C]- and [2-13C]acetate were incorporated in alternate carbon atoms in zearalenone, consistent with the head to tail condensation of nine acetate units. The trichothecenes were enriched in a manner consistent with the condensation of three mevalonate units. 13C/13C couplings, observed between C-5 and C-12, as well as between C-6 and C-15 of 15-acetyldeoxynivalenol, confirms the current hypothesis of formation of the trichothecene ring system by cyclization of farnesyl pyrophosphate. The incorporation pattern in ergosterol is also consistent with a mevalonate origin, while the adjacent incorporation of acetate methyl groups in butenolide suggests a glutamate precursor. The degree of enrichment in the secondary metabolites, which ranged from 3 to 10% at each carbon site, was observed in the 13C NMR spectra of the crude fungal extracts to be dependent on the timing of acetate addition to the culture. The specific toxins produced together with the quantity of each, were also found to be dependent on the timing of acetate addition. Competition between the three biosynthetic pathways of secondary metabolism, i.e. polyketide, mevalonate, and amino acid for the labeled acetate in this organism is a complex function of culture conditions.
747Simultaneous high-performance liquid chromatographic determination of visoltricin, acuminatopyrone and chlamydosporols in Fusarium cultures on maize. Solfrizzo M, Visconti A. J Chromatogr A. 1996 Apr 12;730(1-2):69-73.Visoltricin (VIS), acuminatopyrone (ACP), clamydosporol (CL), isochlamydosporol (ICL) and chlamydospordiol (DIOL), recently characterized Fusarium metabolites, were separated on a polymeric RP-18 column eluted with acetonitrile-0.01% ammonia solution (35:65) at 1 ml/min and detected with a diode-array UV detector. The presence of ammonia in the mobile phase improved the shape of the CL and VIS peaks. The use of a polymeric column was required owing to the basic pH of the mobile phase. Maize cultures of several strains of F.tricinctum and F. chlamydosporum were analysed with this procedure after extraction with aqueous methanol, partitioning with methylene chloride and clean-up with a C18 minicolumn. VIS was produced only by F. tricinctum, whereas ACP and chlamydosporols were produced by both Fusarium species.
748Isolation and characterization of new chlamydosporol related metabolites of Fusarium chlamydosporum and Fusarium tricinctum. Solfrizzo M, Visconti A, Savard ME, Blackwell BA, Nelson PE. Mycopathologia. 1994 Aug;127(2):95-101.Fusarium chlamydosporum strain T-826 isolated from corn in the USA produced chlamydosporol and two analogs which have been identified by various spectroscopic techniques as: 7,8-dihydro-5-hydroxy-4-methoxy-trans-7,8-dimethyl-2H,5H-pyrano(4, 3-b)pyran-2-one (or isochlamydosporol) and 4-methoxy-5-hydroxymethyl-6-(3-butan-2-ol)-2H-pyran-2-one (or chlamydospordiol). Chlamydosporol (compound a + b) chlamydospordiol (compound c) and isochlamydosporol (compound d) were produced together (up to 6000 micrograms/g) by 3 out of 11 isolates of F. chlamydosporum and by 3 out of 24 isolates of F. tricinctum from various substrates and geographic origin. Three isolates of F. chlamydosporum and one isolate of F. tricinctum produced only chlamydospordiol and 2 isolates of F. tricinctum produced chlamydosporol (a + b), and chlamydospordiol (c).
749Occurrence of the mycotoxin chlamydosporol in Fusarium species. Shier WT, Abbas HK.
Toxicon. 1992 Oct;30(10):1295-8.
The mycotoxin chlamydosporol (C11H14O5) has been independently isolated from three different Fusarium species (F. chlamydosporum, F. acuminatum and F. culmorum), suggesting that its distribution may be widespread. We have developed a sensitive, specific fluorometric assay for chlamydosporol that allows quantitation in crude culture extracts. Using this assay we have observed production of chlamydosporol on rice medium by 23 of 40 isolates (58%) of Fusarium sp. examined in amounts as high as 0.8% (wt/wt) dried culture medium
750Fast methods for screening of trichothecenes in fungal cultures using gas chromatography-tandem mass spectrometry. Niels KF, Thran U. J Chromatogr A. 2001 Sep 21;929(1-2):75-87.The paper presents a fast method for trichothecene profiling and chemotaxonomic studies in species of Fusarium, Stachybotrys. Trichoderma and Memnoniella. Micro scale extracted crude Fusarium extracts were derivatised using pentafluoropropionic anhydride and analysed by gas chromatography with simultaneous full scan and tandem mass spectrometric detection. It was possible to monitor for up to four compounds simultaneous, making detection of acetyl T-2 toxin, T-2 toxin, HT-2 toxin, T-2 triol. T-2 tetraol, neosolaniol, iso-neosolaniol, scirpentriol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, 4-acetoxyscirpentriol, nivalenol, fusarenon-X, deoxynivalenol, 15-acetyl-deoxynivalenol and 3-acetyldeoxynivalenol possible during a 23-min GC run. A slightly modified method could detect trichothecenes produced by Stachybotrys, Memnoniella and Trichoderma, by hydrolysing crude extracts prior to derivatisation with heptafluorobuturyl imidazole. All types of derivatised extracts could be reanalysed using negative ion chemical ionisation (NICI) GC-MS for molecular mass determination and verification purposes. A retention time index could be used for correction in retention time drifts between sequences and worked both in EI+ and NICI mode.
751Microbial acetyl conjugation of T-2 toxin and its derivatives. Yoshizawa T, Onomoto C, Morooka N. Appl Environ Microbiol. 1980 May;39(5):962-6.The acetyl conjugation of T-2 toxin and its derivatives, the 12,13-epoxytrichothecene mycotoxins, was studied by using mycelia of trichothecene-producing strains of Fusarium graminearum, F. nivale, Calonectria nivalis, and F. sporotrichoides, T-2 toxin was efficiently converted into acetyl T-2 toxin by all strains except a T-2 toxin-producing strain of F. sporotrichoides, which hydrolyzed the substrate to HT-2-toxin and neosolaniol. HT-2 toxin was conjugated to 3-acetyl HT-2 toxin as an only product by mycelia of F. graminearum and C. nivalis, but was also resistant to conjugation by both F. nivale and F. sporotrichoides. Neosolaniol was also biotransformed selectively into 3-acetyl neosolaniol by F. graminearum. However, 3-acetyl HT-2 toxin was not acetylated by any of the strains under the conditions employed, but was hydrolyzed to HT-2 toxin by F. graminearum and F. nivale. This is the first report on the biological 3 alpha-O-acetyl conjugation of T-2 toxin and its derivatives.
752Production of T-2 toxin by a Fusarium resembling Fusarium poae.Torp M, Langseth W. Mycopathologia. 1999;147(2):89-96.A Fusarium species with a micro morphology similar to F. poae and a metabolite profile resembling that of F. sporotrichioides has been identified. Like typical F. poae, the microconidia have a globose to pyriform shape, but the powdery appearance, especially on Czapek-Dox Iprodione Dichloran agar (CZID), less aerial mycelium and the lack of fruity odour on Potato Sucrose Agar (PSA) make it different from F. poae. The lack of macroconidia, polyphialides and chlamydospores differentiates it from F. sporotrichioides. All 18 isolates investigated, 15 Norwegian, two Austrian and one Dutch, produced T-2 toxin (25-400 micrograms/g) on PSA or Yeast Extract Sucrose agar (YES). In addition, neosolaniol, iso-neosolaniol, HT-2 toxin, 4- and 15-acetyl T-2 tetraol, T-2 triol and T-2 tetraol and 4,15-diacetoxyscirpenol were formed in variable amounts. Neither nivalenol, 4- or 15-acetylnivalenol or 4,15-diacetylnivalenol were detected in any of the cultures, while these toxins were produced at least in small amounts by all the 12 typical F. poae isolates studied. The question of whether this Fusarium should be classified as F. poae or F. sporotrichioides or a separate taxon should be addressed.
753Biosynthesis of the trichothecene 3-acetyldeoxynivalenol. Identification of the oxygenation steps after isotrichodermin. Zamir LO, Devor KA, Sauriol F. J Biol Chem. 1991 Aug 15;266(23):14992-5000.Upon feeding an excess of the substrate isotrichodermin, five tricyclic metabolites accumulated in Fusarium culmorum cultures. These compounds were also identified as transient intermediates of trichothecene biosynthesis by kinetic pulse labeling. Their structures were characterized by spectroscopic techniques (1H NMR, 13C NMR, 2H NMR, and nuclear Overhauser effect difference experiments) as: 1, 15-deacylcalonectrin; 2, calonectrin; 3, 7-hydroxyisotrichodermin; 4, 8-hydroxyisotrichodermin; and 5, 7, hydroxycalonectrin. Four of these metabolites (1-4) were rigorously proven to be biosynthetic precursors to 3-acetyldeoxynivalenol. Indeed, their deuteriated derivatives were shown to be incorporated very efficiently into 3-acetyldeoxynivalenol by 2H-NMR. In addition, our experimental data suggests that the first oxygenation step after isotrichodermin is at C-15, producing 15-deacylcalonectrin.
754Trichothecene mycotoxins from Fusarium culmorum cultures.Baldwin NC, Bycroft BW, Dewick PM, Marsh DC, Gilbert J.Z Naturforsch [C]. 1987 Sep-Oct;42(9-10):1043-9.Chemical analysis of the culture filtrates of Fusarium culmorum CMI 14764 has demonstrated the presence of seven trichothecene mycotoxins. Major metabolites are 3-acetyldeoxynivalenol and 7 alpha, 8 alpha-dihydroxycalonectrin, with 3,15-diacetyldeoxynivalenol, deoxynivalenol, calonectrin, isotrichodermin and 12,13-epoxytrichothec-9-ene (EPT) as minor products. The occurrence of the rarely encountered unsubstituted trichothecene EPT is significant in that this compound may function as a common intermediate in the biosynthetic pathways to all natural trichothecenes. The structures of the known trichothecenes isolated from F. culmorum suggest a route in which EPT is sequentially oxygenated to the more complex deoxynivalenol derivatives.
755The occurrence of culmorin and hydroxy-culmorins in cereals. Ghebremeskel M, Langseth W. Mycopathologia. 2001;152(2):103-8.Forty-five samples from 1988-1995 of naturally contaminated grain, barley, wheat and oats, three samples of mixed feed, and 16 samples of grain artificially inoculated with Fusarium culmorum during the flowering stage were analysed for deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-acetyl-DON), culmorin and hydroxy-culmorins. These compounds are secondary metabolites produced by the fungal species F. culmorum and F. graminearum. Acetonitrile-water extract of the samples was purified on a Mycosep #225 column, derivetized using penta-fluoropropionic anhydride (PFPA) and analysed by gas chromatography-mass spectrometry (GC-MS). The amount of each of culmorin, 5-, 12-, 14 and 15-hydroxy-culmorin and one unknown hydroxy-culmorin were determined relative to the amount of DON plus 3-acetyl DON for each sample. The ratio between the total amount of culmorin compounds and the DON compounds ranged from 0.14 to 1.07 in the samples. This study shows that there is a strong correlation between the amount of DON present in the grain and the amount of culmorin and hydroxy-culmorins present. The ratio of each of the culmorin compounds relative to the amount of DON compounds were in the same range in the grain artificially inoculated by F. culmorum as found in an earlier study for F. culmorum strains cultivated on rice, while the hydroxy-culmorin profile in the naturally contaminated grain was more similar to what was found for the F. graminearum cultures in the same study. These results indicate that F. graminearum may be a relatively important source for DON in grain also in relatively cold areas.
756Mycotoxin producing potential of Fusarium graminearum isolates from Uruguayan barley. Pineiro MS, Scott PM, Kanhere SR. Mycopathologia. 1995-96;132(3):167-72.Twelve isolates of Fusarium graminearum were obtained from barely grains collected from different Uruguayan regions (harvest 1993-94). This was the predominant fungal species contaminating the crop due to a particular humid and warm season with cold nights conductive to toxin production The isolates were grown on moist, sterile rice, extracted with aqueous methanol, and examined for mycotoxin production. Zearalenone (ZEA) and the trichothecenes deoxynivalenol (DON), 3- and 15-acetyl-DON (AcDON), nivalenol (NIV), fusarenon-X (FX) and T-2 toxin (T-2) were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) and confirmed by gas chromatography-mass spectrometry (GC-MS). Eleven of the 12 strains were DON and/or ZEA producers and 9 were AcDON positive. No NIV or FX were detected. One strain produced T-2. The predominant acetyl-DON isomer was 15-AcDON. Mass-spectral analysis yielded detectable levels of other mycotoxins, 13-OH-apotrichothecenes, 11-epiapotrichothecenes, culmorin, sambucinol, and isotrichodermol being the most numerous. From the metabolic profiles it is suggested that Uruguayan F. graminearum strains belong to the chemotype IB (DON/15-AcDON). The predominance of this chemotype is in accordance with data from Canada, United States, Mexico and Argentina which have similar climatic conditions that would favor F. graminearum growth and mycotoxin production.
757Cytotoxicity of trichothecenes and fusarochromanone produced by Fusarium equiseti strains isolated from Norwegian cereals. Morrison E, Rundberget T, Kosiak B, Aastveit AH, Bernhoft A. Mycopathologia. 2002;153(1):49-56.The cytotoxicity and secondary metabolites of 28 Norwegian strains of Fusarium equiseti have been characterized. Trichothecenes and fusarochromanone (FUCH) in rice culture extracts of the strains were analysed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). The following metabolites were found in all isolates: FUCH, nivalenol (NIV), scirpentriol (SCIRP), 4-acetylnivalenol (4-ac-NIV, also called fusarenon-X), 15-acetyl-nivalenol (15-ac-NIV), and diacetoxyscirpenol (DAS). 4,15-diacetyl-nivalenol (diacetyl-NIV) was found in 5 isolates. Porcine kidney epithelial cells (PK15. American Type Culture Collection) were exposed to rice culture extracts to study cytotoxicity. Descriptive statistics and factor analysis of the identified secondary metabolites show that their main metabolites were FUCH, NIV, SCIRP, DAS and 15-ac-NIV, consecutively. The individual trichothecenes were highly intercorrelated, whereas the production of acetylated NIV and DAS was slightly less. Stepwise multiple regression analysis of cytotoxicity and metabolite profiles of rice culture extracts ascribed the toxicity mainly to a combination of FUCH and 15-ac-NIV, though SCIRP or DAS are agents in the combined toxicity as well.
758 Natural contamination of Manitoba barley by 3,15-diacetyldeoxynivalenol and its detection by immunochromatography. Usleber E, Abramson D, Gessler R, Smith DM, Clear RM, Martlbauer E. Appl Environ Microbiol. 1996 Oct;62(10):3858-60.Contamination of Canadian barley samples by 3,15-diacetyldeoxynivalenol was detected by enzyme immunoassays combined with liquid chromatography-mass spectrometry. This is the first reported natural occurrence of this mycotoxin. The barley was infected mainly with Fusarium graminearum. Deoxynivalenol, 3-acetyldeoxynivalenol, and zearalenone were also found.
759Production of culmorin compounds and other secondary metabolites by Fusarium culmorum and F. graminearum strains isolated from Norwegian cereals. Langseth W, Ghebremeskel M, Kosiak B, Kolsaker P, Miller D. Mycopathologia. 2001;152(1):23-34.Twenty-three Fusarium culmorum and 21 F. graminearum isolates were studied for their ability to produce mycotoxins and other secondary metabolites. The strains were cultivated on rice, and the extracts analysed by gas chromatography mass spectrometry (GC-MS) after derivatization with pentafluoropropionic (PFP) reagent. Two F. culmorum strains formed nivalenol and its acetylated derivatives (chemotype II), while all F. graminearum and the other F. culmorum isolates produced deoxynivalenol (DON) via 3-acetyldeoxynivalenol (3-acetyl-DON) (chemotype IA). 15-hydroxy-culmorin, followed by 5-hydroxy-culmorin were the main other metabolites produced F. culmorum, while 5-, 12- and an unidentified hydroxy-culmorin, suggested to be 14-hydroxy-culmorin, were the main metabolites of F. graminearum. The hydroxy-culmorin profile was found to be significantly different for the two Fusarium species. Minor amounts of about ten other hydroxy-culmorins, four hydroxy-culmorones and 3,13-dihydroxy- epiapotrichothecene were also detected in most cultures. Traces of sambucinol seemed to be present in some of the isolates, but were not detected in any significant amounts. The precursors in the biosynthetic sequence to 3-acetyldeoxynivalenol, 7,8-dihydroxycalonectrin and 15-deacetyl-7,8-dihydroxycalonectrin, were detected in most cultures. We also report the assignment of both the 1H and 13C NMR data of 15-deacetyl-7,8-dihydroxycalonectrin, which has only been reported incorrectly before.
760Production of type A trichothecenes and enniatin B by Fusarium sambucinum Fuckel sensu lato. Altomare C, Logrieco A, Bottalico A, Mulé G, Moretti A, Evidente A. Mycopathologia. 1995;129(3):177-81.Twenty-nine Fusarium isolates, representing three new taxa originated by Nirenberg from F. sambucinum Fuckel sensu lato, namely: F. sambucinum Fuckel sensu stricto, F. venenotum Nirenb., and F. torulosum (Berk. & Curt.) Nirenb., were tested for in vitro production of toxic secondary metabolites on autoclaved corn kernels. F. sambucinum sensu stricto was able to produce type A trichothecenes and enniatin B (EB). In particular, amongst the 14 isolates tested, 5 produced only diacetoxyscirpenol (DAS) (up to 700 micrograms/g); 1 produced only neosolaniol (NEOS) (250 micrograms/g); 2 produced T-2 toxin (T-2) + NEOS (up to 175 and 150 micrograms/g, respectively); 1 produced NEOS + DAS (300 and 100 micrograms/g, respectively); and 5 produced DAS + EB (up to 500 and 140 micrograms/g, respectively). All six isolates of F. venenotum were able to produce only DAS (up to 100 micrograms/g). F. torulosum produced no trichothecenes, but four out of nine tested isolates were able to produce EB (up to 140 micrograms/g). Zearalenones and type B trichothecenes were not found. The toxicity of the culture extracts towards Artemia salina L. was correlated in general with the occurrence of the above toxins, except for some F. torulosum strains. However, the lack of correlation between the amounts of toxins recovered and toxic activity observed in the Geotrichum candidum Link ex Pers. and A. salina assays suggested the presence of unknown toxic compounds.
761JM47, a cyclic tetrapeptide HC-toxin analogue from a marine Fusarium species. Jiang Z, Barret MO, Boyd KG, Adams DR, Boyd AS, Burgess JG. Phytochemistry. 2002 May;60(1):33-8.A761:A775The known metabolite, enniatin B, and a cyclic tetrapeptide, JM47, which is a new natural product, were extracted from brown rice cultures of a marine fungus, identified as a Fusarium species, isolated from the marine alga Codium fragile. NMR studies, including 15N HMQC and 15N HMBC, established the structure of JM47 as cyclo(Ala-Ala-Aoh-Pro), where Aoh is the amino acid, (2S,9S)-2-amino-8-oxo-9-hydroxydecanoic acid. The absolute stereochemistry of the Aoh side chain carbinol centre was determined using Mosher ester methodology. Analysis of NOESY data assisted by molecular modelling revealed an alternating L-, D-, L-, D-configuration for the tetrapeptide core. The absolute stereochemistry of the core was determined by acidic hydrolysis and chiral TLC analysis of the proline residue. JM47 belongs to the HC-toxin family of cyclic tetrapeptides which possess a 2-amino-8-oxo-9,10-epoxydecanoic acid residue in place of the Aoh unit. This is the first report of an analogue of HC-toxin from a marine Fusarium species.
762Directed biosynthesis of new enniatins. Krause M, Lindemann A, Glinski M, Hornbogen T, Bonse G, Jeschke P, Thielking G, Gau W, Kleinkauf H, Zocher R. J Antibiot (Tokyo). 2001 Oct;54(10):797-804.New cyclohexadepsipeptides of the enniatin type with potential anthelmintic properties were produced by two different strategies: 1. In vitro synthesis by use of the multienzyme enniatin synthetase, and 2. in vivo precursor feeding of enniatin producing strains Fusarium scirpi and Fusarium sambucinum. The compounds were analyzed by HPLC, various NMR measurements and mass spectrometry. The three N-methyl L-amino acid positions in the enniatin B molecule could be gradually replaced by other (N-methyl) L-amino acids, e.g. alanine, cysteine, threonine and serine. The latter two amino acids yield new enniatins with functional groups in the hydrophobic side chains. Similarly the three D-2-hydroxyisovalerate residues, present in all naturally occuring enniatins, could be substituted by D-2-hydroxybutyric acid and D-lactic acid. Despite its lower yield the in vitro synthesis has the advantage of a broader variety of products formed.
763Discovery and occurrence of the fumonisins: a historical perspective. Marasas WF. Environ Health Perspect. 2001 May;109 Suppl 2:239-43.This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.
764The effects of cereal substrate and temperature on production of beauvericin, moniliformin and fusaproliferin by Fusarium subglutinans ITEM-1434. Kostecki M, Wisniewska H, Perrone G, Ritieni A, Golinski P, Chelkowski J, Logrieco A. Food Addit Contam. 1999 Sep;16(9):361-5.One strain of Fusarium subglutinans (ITEM-1434) isolated from maize ear rot in Poland was tested for the ability to synthesize moniliformin (MON), beauvericin (BEA) and fusaproliferin (FP) on six cereal substrates (wheat, rye, barley, oat, maize and rice kernels) for 3 weeks at 25 degrees C and on rice at three different temperatures (20, 25 and 30 degrees C). Most MON (497 micrograms/g) was produced on rice; most BEA (704 micrograms/g) on wheat or rice, and most FP (422 micrograms/g) on rye. When cultured on rice, F. subglutinans produced the highest levels of BEA and FP at 20-25 degrees C, while MON production was best at 30 degrees C.
765Biological characterization of fusapyrone and deoxyfusapyrone, two bioactive secondary metabolites of Fusarium semitectum.Altomare C, Perrone G, Zonno MC, Evidente A, Pengue R, Fanti F, Polonelli L. J Nat Prod. 2000 Aug;63(8):1131-5.Fusapyrone (1) and deoxyfusapyrone (2), two alpha-pyrones originally isolated from rice cultures of Fusarium semitectum, were tested in several biological assays. Compounds 1 and 2 showed considerable antifungal activity against several plant pathogenic and/or mycotoxigenic filamentous fungi, although they were inactive toward yeasts isolated from plants and the Gram-positive bacterium Bacillus megaterium in disk diffusion assays. Compound 1 was consistently more active than 2. Among the tested fungi, Fusarium species were the least sensitive to the two pyrones, while Alternaria alternata, Ascochyta rabiei, Aspergillusflavus, Botrytis cinerea, Cladosporium cucumerinum, Phoma tracheiphila, and Penicillium verrucosum were the most sensitive. Compounds 1 and 2 also showed good inhibitory activity toward agents of human mycoses. Aspergilli were the most sensitive, while some species-specific variability was found among the Candida spp. In an Artemia salina larvae bioassay, 1 was not toxic at the highest concentration tested (500 microM), whereas the LC(50) of 2 was 37.1 microM (21.8 microg/mL). Neither 1 nor 2 was phytotoxic in a panel of assays that monitored plant-cell toxicity, as well as wilt-, chlorosis-, and necrosis-inducing activity. Moreover, 2 stimulated the root elongation of tomato seedlings at doses of 10 and 100 microM. In consideration of the biological activities evidenced in this study, 1 and 2 appear to be potential candidates for biotechnological applications, as well as good models for studies on mechanism(s) of action and structure-activity relationships.
766Fusapyrone and deoxyfusapyrone, two antifungal alpha-pyrones from Fusarium semitectum. Evidente A, Conti L, Altomare C, Bottalico A, Sindona G, Segre AL, Logrieco A. Nat Toxins. 1994;2(1):4-13.A strain of Fusarium semitectum Berk. & Rav. from maize stalk rot in southern Italy produced bioactive metabolites when cultured on autoclaved rice kernels at room temperature for 4 weeks. The organic extracts of fungal culture showed a strong antibiotic activity towards Geotrichum candidum in disk diffusion assays, but they were not toxic to Artemia salina larvae. Two antifungal metabolites were isolated and characterized by chemical and spectroscopic methods as two 3-substituted-4-hydroxy-6-alkyl-2-pyrones, in particular, the 3-(4-deoxy-beta-xylo-hexopyranosyl)-4-hydroxy-6-[2-hydroxy-7-hydroxymeth yl- 1,1,5,9,11-pentamethyl-3,5,8-heptadecatrienyl]-2H-pyran-2-one and its 6-[2-hydroxy-1,1,5,7,9,11-hexamethyl] analog, which were named fusapyrone and deoxyfusapyrone, respectively.
767Pharmacological activities of fusaric acid (5-butylpicolinic acid). Wang H, Ng TB. Life Sci. 1999;65(9):849-56.This review article aims at summarizing research findings on the various pharmacological activities of fusaric acid (5-butylpicolinic acid), a mycotoxin produced by several Fusarium species which commonly infect cereal grains and other agricultural commodities. The actions of the toxin on mammals, birds, arthropods, crustaceans and plants are covered. The effects on mammals are diverse and are apparent in the nervous, cardiovascular and immune systems. Fusaric acid is toxic to some mammalian tumor cell lines.
768Production of fusaric acid by Fusarium species. Bacon CW, Porter JK, Norred WP, Leslie JF. Appl Environ Microbiol. 1996 Nov;62(11):4039-43.Fusaric acid is a mycotoxin with low to moderate toxicity, which is of concern since it might be synergistic with other cooccurring mycotoxins. Fusaric acid is widespread on corn and corn-based food and feeds and is frequently found in grain, where Fusarium spp. are also isolated. We surveyed 78 strains of Fusarium moniliforme, F. crookwellense, F. subglutinans, F. sambucinum, F. napiforme, F. heterosporum, F. oxysporum, F. solani, and F. proliferatum for their ability to produce fusaric acid. Strains in Fusarium section Liseola also were assigned to mating population of the Gibberella fujikuroi species complex. The fungi could be divided into three classes, low (< 100 micrograms/g), moderate (100 to 500 micrograms/g), and high (> 500 micrograms/g), based on the amounts of this mycotoxin produced in culture on autoclaved corn. Strains of mating populations C from rice consistently produced moderate to high concentrations of fusaric acid. Two isolates, one each from mating populations C and D, produced fusaric acid in excess of 1,000 micrograms/g of corn. No isolates of any of the Fusarium species examined were negative for the production of fusaric acid on autoclaved corn.
769Detection of fusarin C and trichothecenes in Fusarium strains from Spain. Cantalejo MJ, Torondel P, Amate L, Carrasco JM, Hernandez E. J Basic Microbiol. 1999;39(3):143-53.A group of 49 strains of Fusarium sp. isolated from different Spanish samples of cereals and mixed feedstuffs were screened for their ability to produce trichothecenes like T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS) and deoxynivalenol (DN), as well as other mycotoxin produced by Fusarium named fusarin C. The production of these mycotoxins was analyzed by means of spectrophotometry, thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and gas chromatography (GC). Results showed that from 19 Fusarium strains in which cultures trichothecene production was detected, 15 were HT-2 producers, 9 T-2 producers, 14 DAS producers and 10 DN producers. On the other hand, from 28 Fusarium strains in which cultures fusarin C production was detected, 22 were low fusarin C producers (ranged from 0.04 to 1 microgram/l ICI medium), 5 Fusarium strains were intermediate-level producers (ranged from 1 to 10 micrograms/l ICI medium) and one Fusarium strain produced 240 micrograms/l ICI medium. The identified Fusarium strains that produced trichothecenes and fusarin C were F. moniliforme and F. oxysporum.
770Production of fusarin C on cereal and soybean by Fusarium moniliforme. Bacon CW, Marijanovic DR, Norred WP, Hinton DM. Appl Environ Microbiol. 1989 Nov;55(11):2745-8.Two isolates of Fusarium moniliforme were compared with respect to production of a mutagenic compound, fusarin C, on seven corn varieties as well as on soybean, wheat, rye, barley, and a liquid culture medium. The isolates were originally obtained from corn and barley. Both isolates produced fusarin C on seed of all five crops within a 21-day period, and one isolate produced the largest amount on oats. Soybean was the poorest substrate for both isolates. Although the quantity of fusarin C produced on grain was isolate dependent, specific substrate requirements for each strain were suggested. The isolates differed in their ability to grow and produce fusarin C on corn with different moisture contents (16, 20, 24, and 28%). One isolate was more xerotolerant and grew at 16% moisture but did not produce the mutagen.
771Biological and chemical characterization of metabolites of Fusarium moniliforme isolates. Hassanin N, Gabal MA. Vet Hum Toxicol. 1990 Dec;32(6):536-40.Metabolites of fusarium moniliforme isolates from different types of corn were characterized biologically and chemically. The biological assays included rat feeding, rat dermal tests and inoculation of embryonated eggs. Thin-layer chromatography, gas liquid chromatography, and mass spectrophotometry were used to isolate and determine their chemical identities. The metabolites were identified as diacetoxyscripenol, ipomeanol, ipomeanine and diplodiatoxin. The biological tests revealed significant weight loss in rats fed the contaminated corn for 5 w. Hemorrhages and edema in the brain and intestine were detected in all the groups of rats.
772Simultaneous occurrence of fumonisin B1 and other mycotoxins in moldy corn collected from the People's Republic of China in regions with high incidences of esophageal cancer. Chu FS, Li GY. Appl Environ Microbiol. 1994 Mar;60(3):847-52.A total of 31 corn samples collected from households in the counties of Cixian and Linxian of the People's Republic of China, where high incidences of esophageal cancer have been reported, were analyzed for fumonisin B1 (FB1), aflatoxin, and total trichothecene mycotoxins. High levels of FB1 (18 to 155 ppm; mean, 74 ppm) were found in 16 of the samples that showed heavy mold contamination. FB1, at lower levels (20 to 60 ppm; mean, 35.3 ppm), was also found in 15 samples, collected from the same households, that did not show any visible mold contamination. The levels of aflatoxin in the samples were low (1 to 38.4 ppb; mean, 8.61 ppb). High levels of total type-A trichothecenes were also found in the moldy corn samples (139 to 2,030 ppb; mean, 627 ppb). Immunochromatography of selected samples revealed that these samples contained T-2 toxin, HT-2 toxin, iso-neosolaniol, monoacetoxyscirpenol, and several other type-A trichothecenes. The concentration of total type-B trichothecenes in 15 moldy corn samples was in the range of 470 to 5,826 ppb (mean, 2,359 ppb). High levels (3.7 to 5.0 mg/g) of FB1 were produced in corn in the laboratory by five Fusarium moniliforme strains isolated from the moldy corn. These fungi were also capable of forming various nitrosamines (5 to 16 micrograms per flask) in the presence of nitrate and precursor amines.(ABSTRACT TRUNCATED AT 250 WORDS)
806Four new immunosuppressive components, kobiin and kobifuranones A, B, and C, from an ascomycete, Gelasinospora kobi. Fujimoto H, Satoh Y, Yamazaki M. Chem Pharm Bull (Tokyo). 1998 Feb;46(2):211-6.A new sesterterpenetriol named kobiin and three new 2-furanones named kobifuranones A, B, and C were isolated from an Ascomycete, Gelasinospora kobi. Kobiin, the main immunosuppressive principle of this fungus, possesses a bicyclic skeleton of five- and fifteen-membered rings. Kobifuranones A, B, and C were supposed to be metabolites formed from a common intermediate biosynthesized through the acetate-malonate pathway. The immunosuppressive activity of kobiin and kobifuranones A, B, and C was evaluated in a system of mouse spleen lymphocytes stimulated to proliferate with concanavalin A and lipopolysaccharide.
807Immunomodulatory constituents from three ascomycetes, Gelasinospora heterospora, G. multiforis, and G. longispora. Fujimoto H, Sumino M, Nagano J, Natori H, Okuyama E, Yamazaki M.Chem Pharm Bull (Tokyo). 1999 Jan;47(1):71-6.Three new 2-pyrones (2H-pyran-2-ones) called multiforisins G (3), H (1), and I (4), and a known hexaketide sordarial (2) have been isolated from an Ascomycete Gelasinospora heterospora. Among them, 1, 2, and 3 have been proved to be the immunosuppressive components of the fungus. Compounds 1, 3, and 4 have also been isolated from G. multiforis together with multiforisin A (5), which was formerly isolated from this fungus as its main immunosuppressive feature, and 1-5 have also been isolated from G. longispora. The absolute stereostructure of 2, which was not previously certain, has finally been determined to be (3'R,4'S). It has been found that the multiforisins 1, 3, and 5 in which one of the two substituents at positions 3 and 5 is a hydroxymethyl group and the other is a formyl or an acetoxymethyl group, show high immunosuppressive activity; the immunosuppressive activity of 3 does not seem to be due to inhibition of interleukin 2 (IL-2) production.
808Isolation of some immunosuppressive components from an ascomycete, Gelasinospora multiforis. Fujimoto H, Satoh Y, Nakayama M, Takayama T, Yamazaki M. Chem Pharm Bull (Tokyo). 1995 Apr;43(4):547-52.Five new components, named multiforisins A, B, C, D, and E, with immunosuppressive activity were isolated from an Ascomycete, Gelasinospora multiforis. Multiforisin A, the main immunosuppressive principle of this fungus, was deduced to be 5-formyl-3-(hydroxymethyl)-4-methoxy-6-(1E-propenyl)-alpha-pyrone. Multiforisins B, C, D, and E were also deduced to be alpha-pyrone derivatives related to multiforisin A. The IC50 values of multiforisins A, B, C, D, E, and dihydro multiforisin A were evaluated against proliferation of mouse spleen lymphocytes stimulated with concanavalin A and lipopolysaccharide.
813Biodiversity of killer activity in yeasts isolated from the Brazilian rain forest. Buzzini P, Martini A. Can J Microbiol. 2000 Jul;46(7):607-11.The occurrence of killer activity against a panel composed of 22 industrially and (or) medically important yeasts was investigated in 438 yeast and yeast-like cultures belonging to 96 species, isolated from different environments of the Brazilian rain forest. Altogether, 26% of ascomycetes, 56% of basidiomycetes, and 42% of yeast-like cultures exhibited killer activity against at least one of the panel yeasts. More than 15 species never reported before as toxin producers were found, with Pseudozyma antarctica, Trichosporon asteroides, and Geotrichum klebahnii, showing the broader activity spectra. Plasmid curing did not cure the killer phenotypes of Candida maltosa, Debaryomyces hansenii, G. klebahnii, Tr. asteroides, Cryptococcus laurentii, and Ps. antarctica.
820Occurrence of Gibberella zeae strains that produce both nivalenol and deoxynivalenol. Sugiura Y, Watanabe Y, Tanaka T, Yamamoto S, Ueno Y. Appl Environ Microbiol. 1990 Oct;56(10):3047-51.By single ascospore isolation, several sets of asci containing eight ascospores were isolated from perithecia of Gibberella zeae. Of these sets, seven were investigated for their ability to produce 8-ketotrichothecene mycotoxins on rice grains. Analyses were made with gas chromatography-mass spectrometry and gas chromatography with 63Ni electron capture detection. Of 56 total isolates, 11 produced nivalenol, 4-acetylnivalenol, and deoxynivalenol, 1 produced nivalenol and deoxynivalenol, 7 produced deoxynivalenol and 3-acetyldeoxynivalenol, 19 produced deoxynivalenol and 15-acetyldeoxynivalenol, and 6 produced deoxynivalenol and both 15- and 3-acetyldeoxynivalenol. The remaining 12 isolates produced nivalenol and 4-acetylnivalenol. All isolates of G. zeae that we examined could produce 8-ketotrichothecenes in this investigation. This report is the first to demonstrate the presence of G. zeae isolates producing both nivalenol and deoxynivalenol. In addition, differences in the production between 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol are discussed in relation to culture conditions.
821Fusarium species (section Liseola) and its mycotoxins in maize harvested in northern Argentina. Torres AM, Reynoso MM, Rojo FG, Ramirez ML, Chulze SN. Food Addit Contam. 2001 Sep;18(9):836-43.Maize and maize products harvested in small fields and stored by farmers in northern Argentina were assayed for Fusarium and fumonisin and beauvericin contamination. Fumonisins were present in six of the 18 samples. The levels of fumonisins ranged from 603 to 1888 ng/kg. Fumonisin B3 (FB3) and beauvericin were not detected in the samples evaluated. Fusarium subglutinans was one of the most prevalent species isolated. Twenty-five strains of F. subglutinans isolated from maize kernels and belonging to Gibberella fujikuroi mating population E were beauvericin-producers in culture. Seven of these strains also produced moniliformin. This is the first report on beauvericin-production by maize isolates of F. subglutinans from Argentina.
822Identification of deoxynivalenol- and nivalenol-producing chemotypes of Gibberella zeae by using PCR. Lee T, Oh DW, Kim HS, Lee J, Kim YH, Yun SH, Lee YW. Appl Environ Microbiol. 2001 Jul;67(7):2966-72.Gibberella zeae, a major cause of cereal scab, may be divided into two chemotypes based on production of the trichothecenes deoxynivalenol (DON) and nivalenol (NIV). We cloned and sequenced the gene cluster for trichothecene biosynthesis from each chemotype. G. zeae H-11 is a DON producer isolated from corn, and G. zeae 88-1 is a NIV producer from barley. We sequenced a 23-kb gene cluster from H-11 and a 26-kb cluster from 88-1, along with the unlinked Tri101 genes. Each gene cluster contained 10 Tri gene homologues in the same order and transcriptional directions as those of Fusarium sporotrichioides. Between H-11 and 88-1 all of the Tri homologues except Tri7 were conserved, with identities ranging from 88 to 98% and 82 to 99% at the nucleotide and amino acid levels, respectively. The Tri7 sequences were only 80% identical at the nucleotide level. We aligned the Tri7 genes and found that the Tri7 open reading frame of H-11 carried several mutations and an insertion containing 10 copies of an 11-bp tandem repeat. The Tri7 gene from 88-1 carried neither the repeat nor the mutations. We assayed 100 G. zeae isolates of both chemotypes by PCR amplification with a primer pair derived from the Tri7 gene and could differentiate the chemotypes by polyacrylamide gel electrophoresis. The PCR-based method developed in this study should provide a simple and reliable diagnostic tool for differentiating the two chemotypes of G. zeae.
823Ancymidol blocks trichothecene biosynthesis and leads to accumulation of trichodiene in Fusarium sporotrichioides and Gibberella pulicaris. Desjardins AE, Plattner RD, Beremand MN. Appl Environ Microbiol. 1987 Aug;53(8):1860-5.Ancymidol, a plant growth regulator, inhibited biosynthesis of diacetoxyscirpenol by Gibberella pulicaris (Fusarium sambucinum) in a defined liquid medium. Ancymidol also inhibited biosynthesis of T-2 toxin by a wild-type strain of Fusarium sporotrichioides and biosynthesis of diacetoxyscirpenol, deacetylated calonectrin, and dideacetylated calonectrin by mutant strains of this species. Ancymidol-treated cultures accumulated the hydrocarbon trichodiene, a biosynthetic precursor of the trichothecenes. Ancymidol did not block trichodiene accumulation by a trichodiene-producing mutant strain of F. sporotrichioides. Ancymidol appears to block the trichothecene biosynthetic pathway after formation of trichodiene and before formation of trichothecenes containing four or more oxygen atoms.
824Duckling toxicity and the production of fumonisin and moniliformin by isolates in the A and E mating populations of Gibberella fujikuroi (Fusarium moniliforme). Leslie JF, Marasas WF, Shephard GS, Sydenham EW, Stockenström S, Thiel PG. Appl Environ Microbiol. 1996 Apr;62(4):1182-7.Two biological species of Gibberella fujikuroi (A and F mating populations) share the Fusarium moniliforme anamorph. Twenty strains of each of these biological species were tested for the ability to produce fumonisins B1, B2, and B3 and moniliformin and for toxicity to 1-day-old ducklings. Most of the members of the A mating population (19 of 20 strains) produced more than 60 micrograms of total fumonisins per g, whereas only 3 of 20 members of the F mating population produced more than trace levels of these toxins and none produced more than 40 micrograms of total fumonisins per g. In addition, only 3 of 20 members of the A mating population produced more than 1 microgram of moniliformin per g (and none produced more than 175 micrograms/g), while all 20 strains of the F mating population produced more than 85 micrograms of this toxin per g and 1 strain produced 10,345 micrograms/g. The duckling toxicity profiles of the strains of the two mating populations were similar, however, and the level of either toxin by itself was not strongly correlated with duckling toxicity. On the basis of our data we think that it is likely that the members of both of these mating populations produce additional toxins that have yet to be chemically identified. These toxins may act singly or synergistically with other compounds to induce the observed duckling toxicity.
825Biosynthetic and genetic relationships of B-series fumonisins produced by Gibberella fujikuroi mating population A. Proctor RH, Desjardins AE, Plattner RD. Nat Toxins. 1999;7(6):251-8.Fumonisins are mycotoxins produced by the maize pathogen Gibberella fujikuroi mating population A and frequently contaminate maize. Wild-type G. fujikuroi produces four B-series fumonisins, FB1, FB2, FR3 and FB4. These toxins are identical in structure except for the number and positions of hydroxyls along their linear carbon backbone. To elucidate the genetic and biosynthetic relationships among these fumonisins, we conducted meiotic and biochemical analyses of G. fujikuroi mutants with altered fumonisin production that resulted from defective alleles at three loci, Fum1, Fum2 and Fum3. These mutants produced either no fumonisins, only FR2 and FB4, or only FR3 and FR4. Genetic analyses revealed the orientation of the Fum loci along linkage group 1 of the fungus. The mutants were grown together in pair-wise combinations to determine if their fumonisin production phenotypes could be complemented. When FR3- and FB2-producing mutants were grown together, complementation occurred. However, when a nonproducing mutant was grown with a FR2- or FB3-producing mutant, complementation did not occur or was incomplete. When purified FR2, FR3, or FB4 was fed to mutant cultures, FR4 was converted primarily to FR2, FR3 was converted to FB1 and FB2 was not converted. The results from these assays suggest a previously unrecognized branch in the fumonisin biosynthetic pathway.
826Media for identification of Gibberella zeae and production of F-2-(Zearalenone). Bacon CW, Robbins JD, Porter JK. Appl Environ Microbiol. 1977 Feb;33(2):445-9.Media are described for the isolaton of Fusarium graminearum in the perithecial state, Gibberella zeae, and for the production of F-2 (zearalenone) by Fusarium species. On soil extract-corn meal agar isolated medium, G. Zeae produced perithecia in 9 to 14 days under a 12-h photoperiod. Species of Fusarium were screened for F-2 production on a liquid medium. From strains that produced F-2, the yields, from stationary cultures of G. zeae and F. culmorum after 12 days of incubation, ranged from 22 to 86 mg/liter. Three strains produced no F-2. Glumatic acid, starch, yeast extract,and the proper ratio of medium volume-to-flask volume were necessary for F-2 synthesis.
827Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst. III. Production of novel isocoumarin derivatives, isolation, and biological activities. Stadler M, Anke H, Sterner O. J Antibiot (Tokyo). 1995 Mar;48(3):261-6.During investigations on the influence of CaBr2 on the secondary metabolism of Lachnum papyraceum, the production of mycorrhizins and lachnumon type antibiotics was strongly inhibited in bromide-containing culture media. Instead, six isocoumarin derivatives, 6-hydroymellein (6), 4-chloro-6-hydroxymellein (7), 4-bromo-6-hydroxymellein (9), 6-methoxymellein (10). 4-chloro-6-methoxymellein (11), and 4-chloro-6,7-dihydroxymellein (12) were isolated. Compounds 7, 9, 11, and 12 have never been isolated from natural sources. 6-Hydroxymellein has been isolated previously from many sources including Gilmaniella humicola and proposed to be a precursor of mycorrhizin A (see reference 6). In comparison to the mycorrhizins, the isocoumarin derivatives exhibited only weak antimicrobial, cytotoxic, phytotoxic, and nematicidal activities.
828New sequences and new fungal producers of peptaibol antibiotics antiamoebins. Jaworski A, Brückner H. J Pept Sci. 2000 Apr;6(4):149-67.Mixtures of the microheterogeneous 16-mer peptaibol antibiotics called antiamoebins (AAM) have been isolated from the culture broths of strains of the filamentous fungi Stilbella erythrocephala ATCC 28144, Stilbella fimetaria CBS 548.84 and Gliocladium catenulatum CBS 511.66. Sequences were determined using on-line HPLC together with positive- and negative-ion electrospray ionization mass spectrometry. Some characteristic features are recognized in the mass spectrometric fragmentation pattern of AAM. From a sample originally used for sequencing AAM (from Hindustan Antibiotics, Ltd., Pimpri, Poona-411018, India), and a sample of AAM commercially available (from Sigma Chemicals, St. Louis, MO, USA) HPLC elution profiles and sequences were assigned. Further, sequences of AAM previously isolated from Emericellopsis synnematicola CBS 176.60 and Emericellopsis salmosynnemata CBS 382.62 were determined. The peptide designated AAM I was the most abundant in all isolates and its structure could be confirmed. AAM II was detectable as a minor component (1.9%) only in the original sample of AAM, but not in the other isolates. The structures of AAM III, IV and V, which had previously been partly assigned, were definitely established, and the new sequences AAM VI-XVI were elucidated. AAM showing Phe1/Leu1 or Phe1/Val1 exchange, respectively, are produced in amounts only by S. erythrocephala. Sequences, HPLC elution profiles ('fingerprints') and relative amounts of peptides of all isolates were correlated.
829A new sesquiterpene antibiotic, heptelidic acid producing organisms, fermentation, isolation and characterization. Itoh Y, Kodama K, Furuya K, Takahashi S, Haneishi T, Takiguchi Y, Arai M. J Antibiot (Tokyo). 1980 May;33(5):468-73.A new sesquiterpene antibiotic, heptelidic acid, was found in the culture filtrate of three different strains of fungi isolated from soil samples. These strains were identified as Gliocladium virens, Chaetomium globosum and Trichoderma viride. Heptelidic acid was produced by conventional submerged culture and purified by successive column chromatography on silica gel and Sephadex LH-20 and finally by preparative TLC on silica gel. The molecular formula of heptelidic acid was determined as C15H20O5 on the basis of elementary analysis and high resolution mass spectrometry of its monomethyl ester. The antimicrobial spectrum of the antibiotic revealed its specific activity against anaerobic bacteria, especially against Bacteroides fragilis.
830Biosynthesis of Gliorosein in Gliocladium roseum I.M.I. 93065.
Steward MW, Packter NM. Biochem J 1965 Jun;95:26C-28C.
831Studies on the biosynthesis of phenols in fungi. Biosynthesis of 3,4-dimethoxy-6-methyltoluquinol and gliorosein in Gliocladium roseum I.M.I. 93 065. Packter NM, Steward MW. Biochem J. 1967 Jan;102(1):122-32. 
832The structure of gliovirin, a new antibiotic from Gliocladium virens. Stipanovic RD, Howell CR. J Antibiot (Tokyo). 1982 Oct;35(10):1326-30. 
833Glisoprenins C, D and E, new inhibitors of appressorium formation in Magnaporthe grisea, from cultures of Gliocladium roseum. 1. Production and biological activities. Thines E, Eilbert F, Anke H, Sterner O. J Antibiot (Tokyo). 1998 Feb;51(2):117-22.Glisoprenins C, D, and E, new glisoprenin derivatives, were isolated together with glisoprenin A from submerged cultures of the deuteromycete Gliocladium roseum HA190-95. All glisoprenins inhibited appressorium formation in Magnaporthe grisea on inductive (hydrophobic) surfaces. The compounds exhibited moderate cytotoxic, but no antifungal, antibacterial or phytotoxic activities.
834TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282. Kohno J, Asai Y, Nishio M, Sakurai M, Kawano K, Hiramatsu H, Kameda N, Kishi N, Okuda T, Komatsubara S. J Antibiot (Tokyo). 1999 Dec;52(12):1114-23.Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.
835Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazine produced by Gliocladium sp. Chu M, Truumees I, Rothofsky ML, Patel MG, Gentile F, Das PR, Puar MS, Lin SL. J Antibiot (Tokyo). 1995 Dec;48(12):1440-5.Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation of broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3, respectively. Northern analysis revealed the exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction of serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by [3H]uridine incorporation. There results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.
836Interaction of SMKT, a killer toxin produced by Pichia farinosa, with the yeast cell membranes. Suzuki C, Ando Y, Machida S. Yeast. 2001 Dec;18(16):1471-8.SMKT (salt-mediated killer toxin), a killer toxin produced by the halotolerant yeast, Pichia farinosa, kills yeasts of several genera, including Saccharomyces cerevisiae. To elucidate the killing mechanism of SMKT, we examined the interaction of SMKT with membranes using liposomes. Leakage of calcein from calcein-entrapped liposomes was observed in the presence of SMKT. Destruction of liposomes was observed by dark-field microscopy. Comparison of intact S. cerevisiae cells with SMKT-treated cells by dark-field microscopy indicated that the spherical cell membrane is disrupted by SMKT. Using sodium carbonate extraction, we obtained direct evidence for the first time that SMKT is associated with the membrane of sensitive cells. Our results indicate that SMKT kills sensitive S. cerevisiae by interacting with the yeast cell membrane.
837N-glycosylation is involved in the sensitivity of Saccharomyces cerevisiae to HM-1 killer toxin secreted from Hansenula mrakii IFO 0895. Kimura T, Komiyama T, Furuichi Y, Iimura Y, Karita S, Sakka K, Ohmiya K. Appl Microbiol Biotechnol. 1999 Feb;51(2):176-84.Saccharomyces cerevisiae rhk mutants were previously shown to have a phenotype that is resistant to HM-1 killer toxin secreted from Hansenula mrakii IFO 0895. The RHK1/ALG3 gene encodes a mannosyl-transferase that is involved in the synthesis of an oligosaccharide in protein N-glycosylation. Previously, this gene was cloned and shown to complement the rhk1 mutation. In this study, the RHK2 gene, which complements the rhk2 mutation, was cloned. The RHK2 gene was found to be identical to the essential gene STT3, which encodes a subunit of the oligosaccharyl-transferase complex. This complex transfers the core oligosaccharide to proteins. The rhk2 mutants showed supersensitivity to several drugs (Calcofluor White, caffeine and FK506), suggesting that these strains have cell-wall defects. Activity staining of invertase in an acrylamide gel indicated that it was underglycosylated. These results suggest that one or more mannoproteins are involved in the cytocidal process of HM-1.
838Effect of a killer toxin of Pichia anomala to Pneumocystis. Perspectives in the control of pneumocystosis. Séguy N, Polonelli L, Dei-Cas E, Cailliez JC. FEMS Immunol Med Microbiol. 1998 Sep;22(1-2):145-9.Despite the development of drugs in the prophylaxis of pneumocystosis, Pneumocystis carinii remains a major opportunistic microorganism in immunosuppressed individuals, especially in human immunodeficiency virus-infected patients. Since side effects were frequently observed after administration of trimethoprim-sulfamethoxazole or pentamidine, the drugs which are mainly used in treating human P. carinii pneumonia (PCP), new therapeutic strategies should be developed. Over the last years, the inhibitory effect of a Pichia anomala killer toxin (PaKT), a molecule with a wide spectrum of antimicrobial activity, was characterized on P. carinii. The susceptibility of mouse and rat-derived Pneumocystis to PaKT has been demonstrated by in vitro attachment tests and in vivo infectivity assays. Nevertheless, PaKT is strongly antigenic, toxic and could not be used directly as a therapeutic agent. Then, a new strategy using killer toxin-like anti-idiotypic antibodies (KT-antiIds) mimicking the fungal toxin activity has been developed. Different KT-antiIds were obtained by idiotypic immunization with a monoclonal antibody (mabKT4). This mabKT4 neutralized the killer properties of the PaKT. KT-antiIds were produced by immunization against the variable domain (idiotype) of mAbKT4 (internal image of the killer toxin receptor), or they were obtained directly from vaginal fluid of patients affected by recurrent vaginal candidiosis. In this last case, such natural KT-antiIds were immunopurified by affinity-chromatography with mAbKT4 and their anti-P. carinii activity was then evaluated. Our results showed that both the in vitro attachment of rat-derived parasites and their infectivity to nude rats were inhibited by the KT-antiIds. With regard to KT-antiIds obtained by immunization, the antimicrobial activity of a monoclonal KT-antiIds (mAbK10) has been evaluated by using a PCP experimental nude rat model treated by mAbK10 administered by aerosol. The pneumocystosis extension was significantly reduced in this model. The monoclonal KT-antiIds were effective against P. carinii in reducing parasite proliferation in lungs of nude rats. Further experiments are in progress to study the in vivo anti-P. carinii activity of KT-antiIds by using recombinant single-chain of the variable fragment of KT-antiIds. Yeast killer toxin-like recombinant molecules could provide the basis for a new therapeutic strategy towards the control of pneumocystosis.
839Killer toxins of certain yeast strains have potential growth inhibitory activity on gram-positive pathogenic bacteria. Izgü F, Altinbay D. Microbios. 1997;89(358):15-22.The killer yeast strains which are encountered most frequently among species in the genera Saccharomyces, Candida, Hansenula, Pichia and Kluyveromyces (ten killer strains in toto) were tested for the activity of their toxins on the growth of some pathogenic bacteria (four Gram-positive and six Gram-negative strains) in a test in which purified toxins were not required. Neither toxins of the killer Saccharomyces cerevisiae and Pichia membranefaciens strains were active against the bacterial strains. In contrast the killer toxins of Hansenula anamola, Hansenula mrakii, Candida tropicalis, Kluyveromyces drosphilarum and Kluyveromyces lactis showed potential growth inhibitory effects on Gram-positive pathogenic bacteria. Thus, yeast killer toxins were found to be active only on Gram-positive bacterial cell types.
854Convenient procedures for the biosynthesis, isolation, and isotope labeling of cytochalasins. Zabel RA, Miller CA, Tanenbaum SW. Appl Environ Microbiol. 1979 Feb;37(2):208-12.Efforts to improve small-scale yields of useful cytochalasins by fermentation resulted in selection of an enriched aflatoxin medium which increased yields by fivefold over those reported in the literature. With Helminthosporium dematoideum and Zygosporium masonii in stationary culture for 3 weeks, cytochalasins B and D were obtained in quantities approaching 700 and 500 mg/liter, respectively. It appears that the critical component in this growth medium is factors associated with whole wheat. By using these procedures, coupled with improvements in isolation, supplementation with two radioactive phenylalanine species readily produced [14C]- or [3H]cytochalasin B. Oxidation of carrier-free radioactive cytochalasin B to cytochasasin A readily provided this labeled congener as well. The isotopic ocnversion of precursor to crystalline products that met analytical criteria ranged from 2 to 4% of the administered radioactivity.
855 The structure and conformation of HC-toxin. Kawai M, Rich DH, Walton JD. Biochem Biophys Res Commun. 1983 Mar 16;111(2):398-403. 
856 Characteristics of the toxin helminthosporal isolated from culture medium filtrates of Helminthosporium sativum P., K. and B. by extraction with diethyl ether [proceedings] Sommereyns G, Closset JL. Arch Int Physiol Biochim. 1977 Apr;85(2):431-3. 
857 Helminthosporoside, a host-specific toxin from Helminthosporium sacchari. Steiner GW, Strobel GA. J Biol Chem. 1971 Jul 10;246(13):4350-7. 
858 Purification and structure of the host-specific toxin from Helminthosporium carbonum race 1. Walton JD, Earle ED, Gibson BW. 
859In vitro strategies for selection of eye-spot resistant sugarcane lines using toxins of Helminthosporium sacchari. Prasad V, Naik GR. Indian J Exp Biol. 2000 Jan;38(1):69-73.In vitro strategies were applied for the selection of eye-spot resistant variants from susceptible sugarcane cultivar Co 419 Different selective units (callus and leaf) of the susceptible cultivar were subjected to sub-lethal to lethal doses of toxins (culture filtrate and partially purified toxin) of H. sacchari, with the objective of improving the efficacy of in vitro selection protocols. All the selective units gave more or less similar response with culture filtrate, but a distinct response was observed when leaf was subjected to partially purified toxin treatment. The response was characterised by the degree of resistance exhibited by the regenerated seedlings.
860Isolation and characterization of host-selective toxin from Helminthosporium sacchari. Livingston RS, Scheffer RP. J Biol Chem. 1981 Feb 25;256(4):1705-10. 
862 Sativene, Parent of the Toxin from Helminthosporium sativum.
Mayop DE, Williams RE. J AM Chem Soc 1965 Jul 20;87:3275.
863 Comparative biochemistry of the phytopathogenic fungus Helminthosporium. XVI. The production of victoxinine by H. sativum and H. victoriae. Pringle RB. Can J Biochem. 1976 Sep;54(9):783-7. 
864Cloning and mapping of a putative barley NADPH-dependent HC-toxin reductase. Han F, Kleinhofs A, Kilian A, Ullrich SE. Mol Plant Microbe Interact. 1997 Mar;10(2):234-9.The NADPH-dependent HC-toxin reductase (HCTR), encoded by Hm1 in maize, inactivates HC-toxin produced by the fungus Cochliobolus carbonum, and thus confers resistance to the pathogen. The fact that C. carbonum only infects maize (Zea mays) and is the only species known to produce HC-toxin raises the question: What are the biological functions of HCTR in other plant species? An HCTR-like enzyme may function to detoxify toxins produced by pathogens which infect other plant species (R. B. Meeley, G. S. Johal, S. E. Briggs, and J. D. Walton, Plant Cell, 4:71-77, 1992). Hm1 homolog in rice (Y. Hihara, M. Umeda, C. Hara, Q. Liu, S. Aotsuka, K. Toriyama, and H. Uchimiya, unpublished) and HCTR activity in barley, wheat, oats and sorghum have been reported (R. B. Meeley and J. D. Walton, Plant Physiol. 97:1080-1086, 1993). To investigate the sequence conservation of Hm1 and HCTR in barley and the possible relationship of barley Hm1 homolog to the known disease resistance genes, we cloned and mapped a barley (Hordeum vulgare) Hm1-like gene. A putative full-length cDNA clone, Bhm1-18, was isolated from a cDNA library consisting of mRNA from young leaves, inflorescences, and immature embryos. This 1,297-bp clone encodes 363 amino acids which show great similarity (81.6%) with the amino acid sequence of HM1 in maize. Two loci were mapped to barley molecular marker linkage maps with Bhm1-18 as the probe; locus A (Bhm1A) on the long arm of chromosome 1, and locus B (Bhm1B) on the short arm of chromosome 1 which is syntenic to maize chromosome 9 containing the Hm2 locus. The Bhm1-18 probe hybridized strongly to a Southern blot of a wide range of grass species, indicating high conservation of HCTR at the DNA sequence level among grasses. The HCTR mRNA was detected in barley roots, leaves, inflorescences, and immature embryos. The conservation of the HCTR sequence, together with its expression in other plant species (R. B. Meeley and J. D. Walton, Plant Physiol. 97:1080-1086, 1993), suggest HCTR plays an important functional role in other plant species.
895The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms. Peláez F, Cabello A, Platas G, Díez MT, González del Val A, Basilio A, Martán I, Vicente F, Bills GE, Giacobbe RA, Schwartz RE, Onish JC, Meinz MS, Abruzzo GK, Flattery AM, Kong L, Kurtz MB. Syst Appl Microbiol. 2000 Oct;23(3):333-43.In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonema strains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.
900Antifungal metabolites (monorden, monocillin IV, and cerebrosides) from Humicola fuscoatra traaen NRRL 22980, a mycoparasite of Aspergillus flavus sclerotia. Wicklow DT, Joshi BK, Gamble WR, Gloer JB, Dowd PF.The mycoparasite Humicola fuscoatra NRRL 22980 was isolated from a sclerotium of Aspergillus flavus that had been buried in a cornfield near Tifton, Ga. When grown on autoclaved rice, this fungus produced the antifungal metabolites monorden, monocillin IV, and a new monorden analog. Each metabolite produced a clear zone of inhibition surrounding paper assay disks on agar plates seeded with conidia of A. flavus. Monorden was twice as inhibitory to A. flavus mycelium extension (MIC > 28 microg/ml) as monocillin IV (MIC > 56 microg/ml). Cerebrosides C and D, metabolites known to potentiate the activity of cell wall-active antibiotics, were separated from the ethyl acetate extract but were not inhibitory to A. flavus when tested as pure compounds. This is the first report of natural products from H. fuscoatra.
901The effects of space flight on the production of monorden by Humicola fuscoatra WC5157 in solid-state fermentation. Lam KS, Mamber SW, Pack EJ, Forenza S, Fernandes PB, Klaus DM. Appl Microbiol Biotechnol. 1998 May;49(5):579-83.The effect of space flight on the production of the antibiotic monorden on two types of agar media, T8 and PG, by Humicola fuscoatra WC5157 was examined on board the US Space Shuttle mission STS-77 in May 1996. Paired space-flight and ground control samples were prepared using identical hardware, protocol, media, and inoculum. Inoculation occurred simultaneously for both groups 2.5 after launch. The flight and ground samples were allowed to grow for the entire 10-day mission in a dark, thermally controlled (22 degrees C) environment. Post-flight HPLC analysis of the flight and ground sample extracts indicated that the production of monorden by H. fuscoatra WC5157 in the flight samples was higher than in the ground samples in both agar media. In the T8 medium, the production of monorden in the flight and ground samples was 11.6 +/- 3.5 micrograms and 8.9 +/- 1.1 micrograms respectively (30% increase). In the PG medium, the production of monorden in the flight and ground samples was 23.8 +/- 3.3 micrograms and 8.2 +/- 2.2 micrograms respectively (190% increase). The production of monorden in the flight and ground control samples was confirmed by HPLC-MS analysis.
902Xanthoquinodin B3, a new anticoccidial agent produced by Humicola sp. FO-888. Tabata N, Tomoda H, Iwai Y, Omura S. J Antibiot (Tokyo). 1996 Mar;49(3):267-71.Xanthoquinodin B3, a new component of anticoccidial xanthoquinodins, which was detected in the culture broth of Humicola sp. FO-888, was isolated by heat treatment of the xanthoquinodins complex. Structural elucidation indicated that xanthoquinodin B3 has the same heterodimer of xanthone- and anthraquinone-derived monomers as other xanthoquinodins. Schizont formation of monensin-resistant Eimeria tenella in BHK-21 cells was inhibited by xanthoquinodin B3 at concentrations greater than 0.035 microM.
911Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. C, VanMiddlesworth FL, Hensens OD, et al. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):80-4.Three closely related fungal metabolites, zaragozic acids A, B, and C, that are potent inhibitors of squalene synthase have been isolated and characterized. Zaragozic acids A, B, and C were produced from an unidentified sterile fungal culture, Sporormiella intermedia, and Leptodontium elatius, respectively. The structures of the zaragozic acids and their trimethyl esters were determined by a combination of physical and chemical techniques. The zaragozic acids are characterized by a novel 2,8-dioxobicyclo[3.2.1]octane-4,6,7- trihydroxyl-3,4,5-tricarboxylic acid core and differ from each other in the structures of the 6-acyl and 1-alkyl side chains. They were found to be potent competitive inhibitors of rat liver squalene synthase with apparent Ki values of 78 pM, 29 pM, and 45 pM, respectively. They inhibited cholesterol synthesis in Hep G2 cells, and zaragozic acid A was an inhibitor of acute hepatic cholesterol synthesis in the mouse (50% inhibitory dose of 200 micrograms/kg of body weight). Inhibition of squalene synthase in cells and in vivo was accompanied by an accumulation of label from [3H]mevalonate into farnesyl diphosphate, farnesol, and organic acids. These data indicate that the zaragozic acids are a previously unreported class of therapeutic agents with potential for the treatment of hypercholesterolemia.
912Leptosins I and J, cytotoxic substances produced by a Leptosphaeria sp. Physico-chemical properties and structures. Takahashi C, Numata A, Matsumura E, Minoura K, Eto H, Shingu T, Ito T, Hasegawa T. J Antibiot (Tokyo). 1994 Nov;47(11):1242-9.Leptosins I and J, belonging to a series of epipolythiodioxopiperazines, have been isolated from the mycelium of a strain of Leptosphaeria sp. OUPS-4 attached to the marine alga Sargasssum tortile. Their relative stereostructures have been elucidated by chemical and spectral evidence. These compounds exhibited significant cytotoxic activity against cultured P388 cells.
913MK4588, a new antibiotic related to xanthocillin. Itoh J, Takeuchi Y, Gomi S, Inouye S, Mikawa T, Yoshikawa N, Ohkishi H. J Antibiot (Tokyo). 1990 May;43(5):456-61.A new antibiotic, MK4588, structurally related to xanthocillin, was isolated from the culture broth of Leptosphaeria sp. L-179. Antibiotic MK4588 exhibited inhibitory activity against a limited range of Gram-positive and Gram-negative bacteria. The antibiotic was degraded by alkali to a more active product. The structures of MK4588 and the degradation product were determined to be (1R*,6S*,7S*)-7-(Z)-(1-isocyano-2-(4-methoxyphenyl]ethenyl-1-hydro xy-7- isocyanobicyclo[4,2,0]oct-2-en-4-one and (Z)-2,3-diisocyano-1-(4-methoxyphenyl)buta-1,3-diene, respectively, by NMR spectral analyses coupled with X-ray crystallographic analysis of MK4588.
914Leptosphaeria maculans, the causal agent of blackleg disease of Brassicas. Howlett BJ, Idnurm A, Pedras MS. Fungal Genet Biol. 2001 Jun;33(1):1-14.The loculoascomycete Leptosphaeria maculans (anamorph: Phoma lingam) causes blackleg of Brassicas, including Brassica napus (canola or rapeseed). This fungus probably comprises several morphologically similar species; taxonomic relationships between them are being clarified and nomenclature is being revised. The pathotype ("A" group) responsible for major economic losses to canola has been studied in more detail than other members of this species complex and is the focus of this review. L. maculans is haploid, outcrossing, can be transformed, and has a genome size of about 34 Mb. Preliminary genetic and physical maps have been developed and three genes involved in host specificity have been mapped. As yet, few genes have been characterized. Chemical analysis of fungal secondary metabolites has aided understanding of taxonomic relationships and of the host-fungal interaction by the unraveling of pathways for detoxification of antimicrobial phytoalexins. Several phytotoxins (host and nonhost specific) have been identified and a complex pattern of regulation of their synthesis by fungal and host metabolites has been discovered.
915HPLC analyses of cultures of Phoma spp.: differentiation among groups and species through secondary metabolite profiles. Pedras MS, Biesenthal CJ. Can J Microbiol. 2000 Aug;46(8):685-91.The metabolite profiles of 26 isolates of the blackleg fungus (Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode ex Fr.) Desm.), obtained from diverse parts of the world (part of the International Blackleg Crucifer Network collection), were studied utilizing specific culture conditions, HPLC analysis, and a set of chemical markers. This fungus is the causative agent of blackleg disease of brassica oilseeds; a virulent strain of the pathogen has caused significant rapeseed (Brassica napus L., and B. rapa L.) and canola (B. napus L., and B. rapa L.) losses in Canada, and is also considered a serious agricultural problem worldwide. Effective surveys of blackleg epidemics require simple and reliable analytical methodology to differentiate among the diverse groups of isolates. The chemical analysis of phytotoxins and related secondary metabolites is perhaps one of the most discriminating and the least ambiguous methods for differentiation of Phoma blackleg isolates. Following HPLC analyses, the 26 isolates could be placed in three main groups, irrespective of country of origin: isolates producing phomamide and sirodesmins, isolates producing indolyl dioxopiperazines, and isolates producing polyketides. Discussion of the implications of our findings and suggestions for species reclassification are provided.
940A novel quinone antibiotic from Malbranchea cinnamomea TAIM 13T54. Chiung YM, Fujita T, Nakagawa M, Nozaki H, Chen GY, Chen ZC, Nakayama M. J Antibiot (Tokyo). 1993 Dec;46(12):1819-26.A novel quinone antibiotic named malbranicin was isolated from the culture filtrate and mycelium of Malbranchea cinnamomea TAIM 13T54, a thermophilic fungus. The antibiotic was elucidated to be 6-(1-acetylethyl)-2-methoxy-2,5-cyclohexadiene-1,4-dione by spectral analysis. Malbranicin exhibited antimicrobial and cytotoxic activities against Gram-positive bacteria and mammalian cell lines, respectively.
942Toxigenic molds in water-damaged buildings: dechlorogriseofulvins from Memnoniella echinata. Jarvis BB, Zhou Y, Jiang J, Wang S, Sorenson WG, Hintikka EL, Nikulin M, Parikka P, Etzel RA, Dearborn DG. J Nat Prod. 1996 Jun;59(6):553-4.An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, led to the isolation of many isolates of Stachybotrys atra and two isolates of a related toxigenic fungus, Memnoniella echinata. M. echinata produces two cytotoxic trichothecene mycotoxins, trichodermol (1a) and trichodermin (1b), as well as several griseofulvins. Dechlorogriseofulvin (2a) and epidechlorogriseofulvin (2b) were the major compounds isolated. This is the first report of a fungus outside the Penicillium genus producing griseofulvins.
943Study of toxin production by isolates of Stachybotrys chartarum and Memnoniella echinata isolated during a study of pulmonary hemosiderosis in infants. Jarvis BB, Sorenson WG, Hintikka EL, Nikulin M, Zhou Y, Jiang J, Wang S, Hinkley S, Etzel RA, Dearborn D. Appl Environ Microbiol. 1998 Oct;64(10):3620-5.A cluster of cases of pulmonary hemosiderosis among infants was reported in Cleveland, Ohio, during 1993 and 1994. These unusual cases appeared only in infants ranging in age from 1 to 8 months and were characterized by pulmonary hemorrhage, which caused the babies to cough up blood. A case-control study identified major home water damage (from plumbing leaks, roof leaks, or flooding) as a risk factor for development of pulmonary hemorrhage in these infants. Because of an interest in the possibility that trichothecene mycotoxins might be involved in this illness, a number of isolates of Stachybotrys chartarum were grown in the laboratory on rice, and extracts were prepared and analyzed both for cytotoxicity and for specific toxins. Two isolates of Memnoniella echinata, a fungus closely related to S. chartarum, were also included in these studies. S. chartarum isolates collected from the homes were shown to produce a number of highly toxic compounds, and the profiles of toxic compounds from M. echinata were similar; the most notable difference was the fact that the principal metabolites produced by M. echinata were griseofulvins.
944Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2.Vertesy L, Kogler H, Markus A, Schiell M, Vogel M, Wink J. J Antibiot (Tokyo). 2001 Oct;54(10):771-82.The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone. The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide. The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro. This proline-rich peptide is a subsequence of beta-casein. From the observed absence in the literature of any other highly significant sequence homologues, memnopeptide A can be assumed to arise from metabolic products of the fungus with direct incorporation of constituents of the nutrient medium. The formation of memnopeptide A suggests this may be a mechanism for storage of amines by the fungus. Memnopeptide A has weak antibacterial activity against gram-positive bacteria and effects half-maximal activation of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) at a concentration of 12.5 microM.
948Zygosporin D and two new cytochalasins produced by the fungus Metarrhizium anisopliae. Fujii Y, Tani H, Ichinoe M, Nakajima H. J Nat Prod. 2000 Jan;63(1):132-5.Zygosporin D (3) and two new cytochalasins (4 and 5) were isolated from the culture filtrate of the fungus Metarrhizium anisopliae and characterized on the basis of their spectral data and chemical conversions. The new cytochalasins, 4 and 5, were determined to be deacetylcytochalasin C and (6R,16S,18R,21R)-18,21-dihydroxy-16, 18-dimethyl-10-phenyl[11]cytochalasa-13(E),19(E)-diene-1,7,17-trio ne, respectively. Of these three cytochalasins, only zygosporin D is an effective inhibitor of shoot elongation of rice seedlings.
949The novel desmethyldestruxin B2, from Metarhizium anisopliae, that suppresses hepatitis B virus surface antigen production in human hepatoma cells. Chen H, Yeh SF, Ong GT, Wu SH, Sun CM, Chou CK. J Nat Prod. 1995 Apr;58(4):527-31.We have examined the antiviral activity of a crude extract prepared from the culture medium of the fungus Metarhizium anisopliae. Eight active destruxins were identified which showed strong suppressive effect on the production of the hepatitis B surface antigen (HBsAg) in human hepatoma Hep3B cells. One new compound, desmethyldestruxin B2 [1], was isolated from M. anisopliae. This structure was determined based on its nmr and mass spectral data.
950Crystal and molecular structure of Destruxin B. Steiner JR, Barnes CL. Int J Pept Protein Res. 1988 Feb;31(2):212-9.The cyclic hexadepsipeptide mycotoxin Destruxin B, produced by Metarrhizium anisopliae, crystallizes in the orthorhombic space group P212121, with a = 11.010(2)A, b = 14.679(5)A, c = 21.273(7)A and Z = 4. The structure was solved by direct methods and refined by least-squares technique to a final unweighted R value of 0.051, for 3361 reflections with I greater than 3 sigma (I). The backbone of the peptide is asymmetric and is made of 5 trans peptide and ester units and 1 cis peptide unit. The backbone conformation of this cyclic depsipeptide is very similar to that of Roseotoxin B, an analogous mycotoxin produced by Trichothecium roseum. The conformation in the crystalline state also correlates well with the solution conformation, as reported from proton n.m.r. studies. The crystal packing is directed by van der Waals contacts.
951Determination of destruxins, cyclic peptide toxins, produced by different strains of Metarhizium anisopliae and their mutants induced by ethyl methane sulfonate and ultraviolet using HPLC method. Hsiao YM, Ko JL. Toxicon. 2001 Jun;39(6):837-41.Metarhizium anisopliae produces a family of cyclic peptide toxins, destruxins (DTXs), which exhibit various insecticidal activity. Four major DTXs have been separated by HPLC and identified by the liquid chromatography electrospray mass spectrometry (LC-ESI-MS) methods. Strain F061 of M. anisopliae produced large amounts of (DTXs), especially DTX-A (12.84+/-0.04 microg/ml), DTX-B (66.89+/-2.57 microg/ml) and DMDB (1.41+/-0.13 microg/ml). High levels of DTX-E (4.19+/-0.13 microg/ml) were produced by strain F007 of M. anisopliae. The results of our studies also showed that either ethyl methane sulfonate (EMS) or ultraviolet (UV) can significantly increase the production of DTXs. Mutant 61E-9 produced high levels of DTX-A (30.05+/-1.97 microg/ml), DTX-B (110.37+/-10.02 microg/ml) and DMDB (8.30+/-0.45 microg/ml). High levels of DTX-E (20.59+/-2.65 microg/ml) were produced by mutant 7E-3. Both mutant strains are suitable for industrial fermentation processes and possess a wide range of potential applications in the area of metabolic toxin production.
952In vitro effect of fungal cyclodepsipeptides on leukemic cells: study of destruxins A, B and E.Odier F, Vey A, Bureau JP. Biol Cell. 1992;74(3):267-71.The activities of three mycotoxins isolated from the hyphomycete Metarhizium anisopliae: destruxin A, B, and E (DA, DB and DE) are described and compared in vitro on leukemic cells. Their antitumor effect was investigated by flow cytometry on growth, cell viability and cell cycle perturbation 48 h after destruxin exposure. Against P388 leukemic cells, DE displayed greater antiproliferative activity than DA and DB. The minimum concentration required to inhibit 50% of cell proliferation is 0.33 microgram/ml for DE, 11.7 micrograms/ml for DA and 9.4 micrograms/ml for DB. Cell cycle modifications were only observed with DE at 50 and 10 micrograms/ml and consisted in an accumulation of the cells in G0/1 phase. DA and DB did not modify the number of cells in G0/1 of the cell cycle. Nevertheless a decrease in the number of cells in G2+M phase was induced by the three destruxins.
953Destruxin Ed1 a cyclopeptide from the fungus Metarhizium anisopliae. Jegorov A, Sedmera P, Havlícek V, Matha V. Phytochemistry. 1998 Nov;49(6):1815-7.A new destruxin Ed1 has been isolated from the entomopathogenic fungus Metarhizium anisopliae. Its structure was deduced from the NMR and mass spectral data.
954Production of cyclodepsipeptides destruxin A and B from Metarhizium anisopliae. Liu BL, Chen JW, Tzeng YM. Biotechnol Prog. 2000 Nov-Dec;16(6):993-9.Maltose and peptone were the best carbon and nitrogen sources for the production of destruxins from Metarhizium anisopliae. With the addition of 0.1% (w/v) beta-alanine to the basal medium, the yields of cyclodepsipeptides DA and DB were 7.2 and 279 mg/L, respectively, which was 2-fold higher than that of control experiment. Response surface methodology (RSM) was applied to optimize the compositions of maltose, peptone, beta-alanine, and glucose used in a shaker-flask cultivation of M. anisopliae for the production of DA and DB. Estimated optimal compositions for the DA production were maltose 2.58%, peptone 0.72%, beta-alanine 0.02%, and glucose 0.55%. The predicted DA yield was 18.5 mg/L. On the other hand, the optimal compositions for DB production were maltose 2.51%, peptone 0.75%, beta-alanine 0.02%, and glucose 0.43%. A maximum DB yield of 232 mg/L was predicted. These were confirmed by cultivation experiments conducted at the optimized conditions for maximum destruxins production in a shaker-flask. Furthermore, a modest high level of DA (49 mg/L) and DB (268 mg/L) yields were obtained by employing the response surface methodology optimized DB production medium in a no-baffle, stirred-tank fermentor.
956Immunomodulatory constituents from an ascomycete, Microascus tardifaciens. Fujimoto H, Fujimaki T, Okuyama E, Yamazaki M. Chem Pharm Bull (Tokyo). 1999 Oct;47(10):1426-32.Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, questin (emodin 8-O-methylether) (1), rubrocristin (2), 5,7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tradioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (6), tradioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.
965Macrosphelide B suppressed metastasis through inhibition of adhesion of sLe(x)/E-selectin molecules. Fukami A, Iijima K, Hayashi M, Komiyama K, Omura S. Biochem Biophys Res Commun. 2002 Mar 8;291(4):1065-70.Macrosphelide B (MSB), a 16-membered macrolide from Microsphaeropsis sp. FO-5050, inhibits adhesion of sialyl Lewis(x) (sLe(x))-expressing HL-60 cells to LPS-activated (E-selectin-expressing) human umbilical vein endothelial cells (HUVECs) in vitro. This study examines MSB effects on metastasis of B16/BL6 mouse melanoma cells (B16/BL6 cells) and L5178Y-ML mouse lymphoma cells in vivo and analyzes the MSB antimetastatic activity mechanism. When administered MSB at 20 mg/kg/day, lung metastatic nodules of B16/BL6 cells were significantly decreased (T/C = 45%). However, no inhibition of metastasis of L5178Y-ML cells to the spleen and liver was observed. Flow cytometry analysis showed that B16/BL6 cells expressed high levels of sLe(x) antigen, whereas expression on L5178Y-ML cells was low. Under in vitro conditions, B16/BL6 cells demonstrated a greater degree of adhesion to LPS-activated HUVECs than L5178Y-ML cells, but adhesion was significantly inhibited by MSB and sLe(x) antibody. Combined therapy of MSB and cisplatin (CDDP) induced remarkable lung metastasis inhibition without adverse effects of CDDP to the host. All these findings suggest that MSB suppresses lung metastasis of B16/BL6 cells by inhibiting cell adhesion to endothelial cells through the sLe(x) molecule.
966Microsphaerones A and B, two novel gamma-pyrone derivatives from the sponge-derived fungus Microsphaeropsis sp. Wang CY, Wang BG, Brauers G, Guan HS, Proksch P, Ebel R. J Nat Prod. 2002 May;65(5):772-5.Two new metabolites, microsphaerones A (1) and B (2), were identified from the EtOAc extract of the culture of an undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba. Compounds 1 and 2 represent the first examples of gamma-pyrone derivatives of the fungal genus Microsphaeropsis. The structures of the compounds were elucidated on the basis of comprehensive spectral analysis ((1)H, (13)C, (1)H-(1)H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution ESI and EIMS experiments). The (S)-2-methylsuccinic acid moiety present in 1 was established by GC-MS analysis of a hydrolysis product.
967A new anti-influenza virus antibiotic, 10-norparvulenone from Microsphaeropsis sp. FO-5050. Fukami A, Nakamura T, Kim YP, Shiomi K, Hayashi M, Nagai T, Yamada H, Komiyama K, Omura S. J Antibiot (Tokyo). 2000 Oct;53(10):1215-8. 
968TAN-1496 A, C and E, diketopiperazine antibiotics with inhibitory activity against mammalian DNA topoisomerase I. Funabashi Y, Horiguchi T, Iinuma S, Tanida S, Harada S. J Antibiot (Tokyo). 1994 Nov;47(11):1202-18.Fungal metabolites with an epi-oligothiadiketopiperazine structure, TAN-1496 A, C and E, were isolated from the culture broth of Microsphaeropsis sp. FL-16144. Their molecular formulas were determined to be C22H28N2O9S2, C22H28N2O9S3 and C22H28N2O9S4, respectively. Structures were determined by comparing the NMR data with those of known diketopiperazine antibiotics, sirodesmins. These metabolites inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I but did not affect the decatenation of kinetoplast DNA by calf thymus topoisomerase II at concentration up to 500 microM. They strongly suppressed the growth of various murine and human tumor cells and induced apoptosis. Moreover, various derivatives were synthesized to investigate the relationship of their functional groups and biological activities.
987Medium-chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber. Hajjaj H, Klaébé A, Goma G, Blanc PJ, Barbier E, François J. Appl Environ Microbiol. 2000 Mar;66(3):1120-5.During submerged culture in the presence of glucose and glutamate, the filamentous fungus Monascus ruber produces water-soluble red pigments together with citrinin, a mycotoxin with nephrotoxic and hepatoxic effects on animals. Analysis of the (13)C-pigment molecules from mycelia cultivated with [1-(13)C]-, [2-(13)C]-, or [1, 2-(13)C]acetate by (13)C nuclear magnetic resonance indicated that the biosynthesis of the red pigments used both the polyketide pathway, to generate the chromophore structure, and the fatty acid synthesis pathway, to produce a medium-chain fatty acid (octanoic acid) which was then bound to the chromophore by a trans-esterification reaction. Hence, to enhance pigment production, we tried to short-circuit the de novo synthesis of medium-chain fatty acids by adding them to the culture broth. Of fatty acids with carbon chains ranging from 6 to 18 carbon atoms, only octanoic acid showed a 30 to 50% stimulation of red pigment production, by a mechanism which, in contrast to expectation, did not involve its direct trans-esterification on the chromophore backbone. However, the medium- and long-chain fatty acids tested were readily assimilated by the fungus, and in the case of fatty acids ranging from 8 to 12 carbon atoms, 30 to 40% of their initial amount transiently accumulated in the growth medium in the form of the corresponding methylketone 1 carbon unit shorter. Very interestingly, these fatty acids or their corresponding methylketones caused a strong reduction in, or even a complete inhibition of, citrinin production by M. ruber when they were added to the medium. Several data indicated that this effect could be due to the degradation of the newly synthesized citrinin (or an intermediate in the citrinin pathway) by hydrogen peroxide resulting from peroxisome proliferation induced by medium-chain fatty acids or methylketones.
988Metabolites of Monascus ruber in silages. Schneweis I, Meyer K, Hörmansdorfer S, Bauer J. J Anim Physiol Anim Nutr (Berl). 2001 Feb;85(1-2):38-44.A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 x 10(3) and 9 x 10(6) colony-forming units (CFU)/g (mean: 2 x 10(5) CFU/g). Monacolin K(L) and the hydroxy acid monacolin K(A) were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25-15 600 and 28-65 400 microg/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2 microg/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin K(A) and monacolin K(L) occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.
989New monascus metabolite isolated from red yeast rice (angkak, red koji). Wild D, Tóth G, Humpf HU. J Agric Food Chem. 2002 Jul 3;50(14):3999-4002.Red yeast rice (angkak, red koji) obtained as cultures of Monascus purpureus on rice was extracted and analyzed by HPLC. In addition to the known red, orange, and yellow pigments and the mycotoxin citrinin, a new Monascus metabolite was detected. It is present in the original red yeast rice and formed in higher amounts when red yeast rice is heated. High-resolution mass spectrometry indicated the molecular formula C(15)H(12)O(4). The chemical structure was elucidated by analysis of NMR data. The new compound, named monascodilone, is characterized by a propenyl group on a pyrone ring, an aromatic ring, and a gamma-lactone group.
991Identification of sterigmatocystin as a metabolite of Monocillium nordinii. Ayer WA, Pena-Rodriguez L, Vederas JC. Can J Microbiol. 1981 Aug;27(8):846-7. 
992Observations on the experimental pathogenicity and toxigenicity of Mortierella wolfii strains of bovine origin. Corbel MJ, Eades SM. Br Vet J. 1991 Nov-Dec;147(6):504-16.Four strains of Mortierella wolfii isolated from cattle in Britain were compared in pathogenicity and toxigenicity with a strain isolated from a cow with the mycotic abortion-pneumonia syndrome in New Zealand. All strains produced acute lethal infection in rabbits after intravenous inoculation of mycelial suspensions and all produced subacute mycotic encephalitis in mice after intracerebral injection. They also produced an acid-stable, heat- and trypsin-labile toxin in vitro. The action of the toxin was exerted mainly on the kidneys in rabbits and mice and produced effects distinct from those resulting from infection with M. wolfii.
993Localisation and pathology of Mortierella wolfii toxin in mice. Davey G, Simpson LO, Kalmakoff J. J Pathol. 1975 Sep;117(1):33-7.Using 125I labelled M. wolfii toxin the site of action in mice was shown to be the kidney. Autoradiographic studies revealed the label to be localised in the proximal convoluted tubules of the kidney, where there was a marked necrosis and degeneration of the epithelium causing the tubules to become considerably distended. Although the distal and collecting tubules maintained their integrity, many contained amorphous casts. An injected dose of 1 toxic unit (10 mug protein) was sufficient to produce damage to the kidney with subsequent anaemia, azotemia and albuminuria. Other organs appeared to be essentially normal and renal failure was the probable cause of death of mice.
994Purification and properties of a toxin isolated from Mortierella wolfii. Davey G, Smith JM, Kalmakoff J. Infect Immun. 1973 Dec;8(6):882-6. 
995Evidence that the nephrotoxin from the fungus Mortierella wolfii is a protein. Davey G, Kalmakoff J. Can J Microbiol. 1974 Nov;20(11):1513-6 
1011A novel bioactive delta lactone FD-211. Taxonomy, isolation and characterization. X; He, B M; Mizoue, K. Nozawa O, Okazaki T, Sakai N, Komurasaki T, Hanada K, Morimoto S, Chen ZX, He BM, Mizoue K. J Antibiot (Tokyo). 1995 Feb;48(2):113-8.During our screening program for natural product drugs effective against multidrug-resistant mammalian cells, we have discovered a new delta lactone FD-211 from the fermantation broth of Myceliophthora lutea TF-0409. FD-211 had a broad spectrum activity against cultured tumor cell lines, including adriamycin-resistant HL-60 cells.
1012Waol B, a new trihydrofuran derivative with cytocidal activity, isolated from Myceliophthora lutea. Nozawa O, Okazaki T, Morimoto S, Chen ZX, He BM, Mizoue K. J Antibiot (Tokyo). 2000 Nov;53(11):1296-300. 
1016Trichoverroid stereoisomers.Jarvis BB, Wang S, Ammon HL. J Nat Prod. 1996 Mar;59(3):254-61.Trichoverroids, which lie along the biosynthetic path between the simple and the macrocyclic trichothecenes, have been characterized previously as sets of diastereomers that have the S-configuration at C-6' and are epimeric at C-7'. An isolate of Myrothecium verrucaria (ATCC 20540), which is the only species of Myrothecium reported to produce the macrocyclic trichothecene isororidin E (3a), produces trichoverrols (1) and trichoverrins (2) that are epimeric at C-7' but that have R-configurations at the C-6' centers. Also reported are several additional naturally occurring C6'R-series trichoverroids that have varied structural modifications, including several E,Z-isomers 7-9, 9 beta,10 beta-epoxides 11a and b, 12,13-deoxyisotrichoverrin B (10), and 8 alpha-hydroxyisotrichoverrin A (12).
1017A new macrocyclic trichothecene, 12,13-deoxyroridin E, produced by the marine-derived fungus Myrothecium roridum collected in Palau. amikoshi M, Akano K, Meguro S, Kasuga I, Mine Y, Takahashi T, Kobayashi H. J Nat Prod. 2001 Mar;64(3):396-8.A new macrocyclic trichothecene, 12,13-deoxyroridin E (1), and three known compounds, roridin E (2), verrucarin A (3), and verrucarin J (4), were obtained as cytotoxic components from the marine-derived fungus Myrothecium roridum, isolated in Palau. 12,13-Deoxyroridin E is the second example of a macrocyclic trichothecene possessing a double bond at C-12-C-13 and was about 80-fold less cytotoxic than roridin E, the epoxide variant.
101812,13-Deoxytrichoverrins from Myrothecium verrucaria.Jarvis BB, Midiwo JO, Guo MD. J Nat Prod. 1989 May-Jun;52(3):663-5. 
101914'-Hydroxymytoxin B and 16-hydroxyroridin E, two new cytotoxic trichothecenes from Myrothecium roridum. Alvi KA, Rabenstein J, Woodard J, Baker DD, Bergthold JD, Lynch J, Lieu KL, Braude IA. J Nat Prod. 2002 May;65(5):742-4.Two new trichothecenes, 14'-hydroxymytoxin B (1) and 16-hydroxyroridin E (3), were isolated from a fermentation extract of Myrothecium roridum. The structures of 1 and 3 were determined by spectral data interpretation. Both compounds showed potent cytotoxic activity against primary soft-tissue sarcoma cells.
1020New trichoverroids from Myrothecium verrucaria: 16-hydroxytrichodermadienediols. Jarvis BB, Vrudhula VM. J Antibiot (Tokyo). 1983 Apr;36(4):459-61. 
1021Phytotoxicity and mammalian cytotoxicity of macrocyclic trichothecene mycotoxins from Myrothecium verrucaria. Abbas HK, Johnson BB, Shier WT, Tak H, Jarvis BB, Boyette CD. Phytochemistry. 2002 Feb;59(3):309-13.Macrocyclic trichothecene toxins produced by Myrothecium verrucaria (a phytopathogen of interest in biological weed control) and the non-trichothecene toxin atranone B from Stachybotrys atra were tested for phytotoxicity in duckweed (Lemna pausicostata L.) plantlet cultures and kudzu (Pueraria lobata L.) leaf disc assays, and for mammalian cytotoxicity in four cultured cell lines. Roridin E and H, epi-isororidin E, and verrucarin A and J were phytotoxic (half-maximal effect in the concentration range 0.1-9.7 microM on duckweed and 1.5->80 microM on kudzu) and cytotoxic to mammalian cell lines (half-maximal inhibition of proliferation in the concentration range 1-35 nM). Trichoverrins A and B and atranone B were moderately phytotoxic (half-maximal effect in the concentration range 1 9-69 microM on duckweed and 13->80 microM on kudzu) and weakly cytotoxic with mammalian cell lines (half-maximal inhibition of proliferation in the concentration range 0.3->2 microM).
1022Roridin L, M and verrucarin M, new macrocyclic trichothecene group antitumor antibiotics, from Myrothecium verrucaria. Murakami Y, Okuda T, Shindo K. J Antibiot (Tokyo). 2001 Nov;54(11):980-3. 
1023Structure of roridin J, a new macrocyclic trichothecene from Myrothecium verrucaria. Jarvis BB, Stahly GP, Pavanasasivam G, Mazzola EP. J Antibiot (Tokyo). 1980 Feb;33(2):256-8. 
1025Myxostiolide, myxostiol, and clavatoic acid, plant growth regulators from the fungus Myxotrichum stipitatum. Kimura Y, Shimada A, Kusano M, Yoshii K, Morita A, Nishibe M, Fujioka S, Kawano T. J Nat Prod. 2002 Apr;65(4):621-3.New plant growth regulators, named myxostiolide (1), myxostiol (2), and clavatoic acid (3), have been isolated from Myxotrichum stipitatum, and their structures have been established by spectroscopic methods including 2D NMR. The biological activities of 1, 2, and 3 have been examined using tea pollen and lettuce seedling bioassay methods. With tea pollen, compound 1 inhibited the pollen tube growth to 14% of control at a concentration of 100 mg/L. With lettuce seedlings, compound 2 accelerated the root growth from 1 mg/L to 100 mg/L and compound 3 inhibited the root growth, to 52% of control, at a concentration of 100 mg/L.
1026Antitumor effect of keto-diepoxides isolated from the fungus Nattrassia mangiferae. King I, Blood C, Chu M, Patel M, Liu M, Li Z, Robertson N, Maxwell E, Catino JJ. Oncol Res. 1995;7(1):1-5.A novel keto-diepoxide Sch 49209 and its derivative Sch 50672, produced by the fungus Nattrassia mangiferae, inhibited tumor cell invasion through an artificial basement membrane. These compounds, at nontoxic concentrations, inhibited invasion of HT-1080 cells in a dose-dependent manner. The IC50 values for Sch 49209 and Sch 50672 were 0.75 and 8 microM, respectively, when cells were incubated with drugs for 5 h. Sch 49209 inhibited both tumor cell invasion and cell motility to the same extent under conditions that did not cause any apparent cytotoxicity. Sch 4209 and Sch 50672, however, inhibited the growth of ras-transformed cells in a semisolid medium in a 5-day culture with IC50 values of 0.6 and 2.4 microM, respectively. They also inhibited the anchorage-dependent growth of pT24 cells in vitro with IC50 values of 0.5 and 0.9 microM for Sch 40209 and Sch 50672, respectively. Using the murine lung epidermoid carcinoma M27 cells implanted SC in mice as a model, we found both Sch 49209 and Sch 50672 inhibited the growth of this tumor at doses ranging from 2 to 10 mg/kg. These compounds also decreased the formation of spontaneous lung metastasis in this model. Sch 50672 inhibited the growth of human tumor xenografts, SW620 and A431, in athymic mode mice. Our data suggest that keto-diepoxides inhibit tumor growth and metastasis and that this activity may be due, in part, to anti-invasive activity.
1034Metabolites of Pyrenomycetes V. Identification of an antibiotic from two species of Nectria, as cephalochromin. Carey ST, Nair MS. Lloydia. 1975 Sep-Oct;38(5):448-9. 
1035A new deoxyfusarubin produced by the fungus Nectria haematococca. Synthesis of the two isomeric deoxyanhydronaphthopyranones from toralactone. Parisot D, Devys M, Barbier M. J Antibiot (Tokyo). 1992 Nov;45(11):1799-801. 
1036A new immunomodulator, FR-900483. Shibata T, Nakayama O, Tsurumi Y, Okuhara M, Terano H, Kohsaka M. J Antibiot (Tokyo). 1988 Mar;41(3):296-301.FR-900483 is a new immunoactive substance produced by a fungus, Nectria lucida F-4490. Concanavalin A-stimulated lymphocyte proliferation, which had been suppressed by addition of immunosuppressive factor, was restored to a normal level by the addition of FR-900483. Furthermore, FR-900483 restored the capacity of immunosuppressed mice to produce antibody against sheep red blood cells.
1037Fusarin C, (7Z)-fusarin C and (5Z)-fusarin C; inhibitors of dihydroxynaphthalene-melanin biosynthesis from Nectria coccinea (Cylindrocarpon sp.). Eilbert F, Thines E, Arendholz WR, Sterner O, Anke H. J Antibiot (Tokyo). 1997 May;50(5):443-5. 
1038Haematocin, a new antifungal diketopiperazine produced by Nectria haematococca Berk. et Br. (880701a-1) causing nectria blight disease on ornamental plants. Suzuki Y, Takahashi H, Esumi Y, Arie T, Morita T, Koshino H, Uzawa J, Uramoto M, Yamaguchi I. J Antibiot (Tokyo). 2000 Jan;53(1):45-9.A new antifungal diketopiperazine named haematocin was isolated from the culture broth of Nectria haematococca Berk. et Br. (880701a-1) causing blight disease on ornamental plants, Phalaenopsis spp. and Doritanopsis spp. Its structure was established by spectroscopic methods. Haematocin inhibited the germ-tube elongation and spore-germination of Pyricularia oryzae at the ED50 values of 30 microg/ml and 160 microg/ml, respectively.
1039Metabolites from Pyrenomycetes VIII. Identification of three metabolites from Nectria lucida as antibiotic triprenyl phenols. Carey ST, Nair MS. Lloydia. 1977 Nov-Dec;40(6):602-3. 
1040Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis. Oikawa T, Ito H, Ashino H, Toi M, Tominaga T, Morita I, Murota S. Eur J Pharmacol. 1993 Sep 14;241(2-3):221-7.Angiogenesis plays a significant role in various pathological states, including the progressive growth of solid tumors, rheumatoid arthritis, psoriasis, and diabetic retinopathy, in addition to its crucial role in embryonic development. Recent studies have revealed that an angiogenesis inhibitor is efficacious for these so-called angiogenic diseases. In the previous studies, we found that retinoids and vitamin D3 analogs, which are known to exhibit cell differentiation-modulating activity, effectively inhibit angiogenesis in vivo, thus forming the basis of our working hypothesis that a modulator of cell differentiation is capable of affecting angiogenesis. In this study, to verify this hypothesis further, radicicol (syn. monorden; 5-chloro-6-(7,8-epoxy-10-hydoxy-2-oxo-3,5-undecadienyl)-beta -resorcylic acid mu-lactone), a microbial cell differentiation modulator from a fungus, a strain of Neocosmospora tenuicristata, was examined for its anti-angiogenic activity in a bioassay system involving chorioallantoic membranes of growing chick embryos. The microbial cell differentiation modulator dose dependently inhibited embryonic angiogenesis, the ID50 value being 200 ng/egg. Radicicol also inhibited both the proliferation of and plasminogen activator production by vascular endothelial cells in the nM concentration range in a concentration-dependent manner, suggesting the possible involvement of these inhibitory effects in the anti-angiogenic action of the microbial product. These results indicate that radicicol might be a potential drug for treating different angiogenesis-dependent diseases, such as solid tumors, psoriasis, rheumatoid arthritis, and diabetic retinopathy.
1044Structure of fischerin, a new toxic metabolite from an ascomycete, Neosartorya fischeri var. fischeri. Fujimoto H, Ikeda M, Yamamoto K, Yamazaki M. J Nat Prod. 1993 Aug;56(8):1268-75.A new toxic metabolite named fischerin [1] from an Ascomycete. Neosartorya fischeri var. fischeri, which caused lethal peritonitis in mice, was deduced to have a structure including a 1,4-dihydroxy-3,5-disubstituted-2(1H)-pyridone moiety by chemical and spectral data.
1045Growth of and fumitremorgin production by Neosartorya fischeri as affected by temperature, light, and water activity. Nielsen PV, Beuchat LR, Frisvad JC. Appl Environ Microbiol. 1988 Jun;54(6):1504-10.The effects of temperature, light, and water activity (aw) on the growth and fumitremorgin production of a heat-resistant mold, Neosartorya fischeri, cultured on Czapek Yeast Autolysate agar (CYA) were studied for incubation periods of up to 74 days. Colonies were examined visually, and extracts of mycelia and CYA on which the mold was cultured were analyzed for mycotoxin content by high-performance liquid chromatography. Growth always resulted in the production of the tremorgenic mycotoxins verruculogen and fumitremorgins A and C. The optimum temperatures for the production of verruculogen and fumitremorgins A and C on CYA at pH 7.0 were 25, 30, and 37 degrees C, respectively. The production of fumitremorgin C by N. fischeri has not been previously reported. Fumitremorgin production was retarded at 15 degrees C, but an extension of the incubation period resulted in concentrations approaching those observed at 25 degrees C. Light clearly enhanced fumitremorgin production on CYA (pH 7.0, 25 degrees C), but not as dramatically as did the addition of glucose, fructose, or sucrose to CYA growth medium (pH 3.5, 25 degrees C). Growth and fumitremorgin production was greatest at aw of 0.980 on CYA supplemented with glucose or fructose and at aw of 0.990 on CYA supplemented with sucrose. Growth and fumitremorgin production were observed at aw as low as 0.925 on glucose-supplemented CYA but not at aw lower than 0.970 on CYA supplemented with sucrose. Verruculogen was produced in the highest amount on all test media, followed by fumitremorgin A and fumitremorgin C.
1046Production of type II ribotoxins by Aspergillus species and related fungi in Taiwan. Lin A, Huang KC, Hwu L, Tzean SS. Toxicon. 1995 Jan;33(1):105-10.A molecular investigation was conducted on the production of type II ribotoxin of the species Aspergillus and related fungi in Taiwan. Species that carried ribotoxin were confirmed by (1) cross-reactivity to anti-alpha-sarcin serum; (2) Southern dot hybridization; (3) PCR amplification of genomic DNA with specific primers; and (4) analysis of ribotoxic activity. Five new strains, A. clavatus, A. oryzae var. effusus, A. ostianus, A. tamarii, and Neosartorya fischeri var. spinosa, were identified to contain an alpha-sarcin-like ribotoxin. These positive strains exhibit ribotoxic activity by cleaving ribosomes and generating an alpha-fragment.
1047Azaspirene: a novel angiogenesis inhibitor containing a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton produced by the fungus Neosartorya sp. Asami Y, Kakeya H, Onose R, Yoshida A, Matsuzaki H, Osada H. Org Lett. 2002 Aug 22;4(17):2845-8.[structure: see text] Azaspirene isolated from the fungus Neosartorya sp. is a novel angiogenesis inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton. Azaspirene inhibits the endothelial migration induced by vascular endothelial growth factor (ED100 = 27.1 microM).
1048Fiscalins: new substance P inhibitors produced by the fungus Neosartorya fischeri. Taxonomy, fermentation, structures, and biological properties. Wong SM, Musza LL, Kydd GC, Kullnig R, Gillum AM, Cooper R. J Antibiot (Tokyo). 1993 Apr;46(4):545-53.Three new compounds, named fiscalins A, B, and C, were found in culture broth produced by a Neosartorya fischeri. These compounds inhibit the binding of radiolabeled substance P ligand to the human neurokinin (NK-1) receptor, with Ki values of 57, 174, and 68 microM, respectively. Detailed spectroscopic and amino acid analyses led to the elucidation of structures for the three fiscalins. The structures contain an indolyl moiety linked to an athranilic acid derived tricyclic system. The absolute configuration of fiscalin A was determined by X-ray crystallography and chiral amino acid analysis. The presence of fiscalins was detected directly in crude cellular extracts using LC-MS methods.
1049Identification of the configuration of neosartorin by long-range nuclear Overhauser effect measurements. Liptaj T, Pham TN, Proksa B, Uhrín D. Chirality. 2001;13(9):545-7.The relative configuration of the two xanthene units of neosartorin, a new ergochrome biosynthesised by the soil mould Neosartorya fischeri, was determined using a 1D double-pulsed field gradient spin-echo NOESY experiment. It was found that both units have the same relative stereochemistry. Long-range nonbonding interactions between the substituents of different xanthene units stabilise the nonplanar configuration of the two aromatic rings A and A' connecting both monomer units of neosartorin.
1059A toxic metabolite of Nigrospora oryzae (Berk and Br.) petch. Wilson ME, Davis ND, Diener UL. Mycopathologia. 1986 Sep;95(3):133-8.Nigrospora oryzae was isolated from dallisgrass (Paspalum dilatatum Poir.) collected in Auburn and from hay shipped under refrigeration to Florida. Some of these samples were eaten by cattle and horses that subsequently developed lameness. Metabolites of N. oryzae were separated by thin layer chromatography and tested for toxicity. Only one metabolite was toxic. Metabolite A showed toxicity to brine shrimp with an LD50 = 500 micrograms/ml in 8 h. It also had an antibiotic effect on Bacillus megaterium ATCC 14581 with a minimum inhibitory level of 10.1 micrograms/disc. As little as 435 micrograms of a crude methanolic extract of N. oryzae showed mild toxicity to chick embryos. The metabolite was not toxic to mice nor rats at the levels tested. Quantitative procedures developed for the determination of metabolite A showed that the maximum production occurred in yeast extract-sucrose liquid medium with an initial pH of 5-6, when incubated as a stationary culture for 28 days at 25 degrees C. It was concluded that metabolite A is a weak antibiotic rather than a mycotoxin, and was probably not associated with the symptoms of lameness observed in cattle and horses. The antibiotic is not one previously reported for N. oryzae.
1062Nodulisporic acid B, B(1), and B(2): a series of 1'-deoxy-nodulisporic acids from Nodulisporium sp. Ondeyka J, Dahl-Roshak A, Tkacz J, Zink D, Zakson-Aiken M, Shoop W, Goetz M, Singh S. Bioorg Med Chem Lett. 2002 Oct 21;12(20):2941.During the re-isolation of the lead compound nodulisporic acid A (1a) and targeted chemical screening for related compounds, we discovered a series of 1'-deoxy congeners named herein nodulisporic acids B (1b), B(1) (2b), and B(2) (3b). In comparison with nodulisporic acid A, these compounds were less active and were chemically unstable resulting into formation of Delta(23) dehydro derivatives. Therefore, these compounds were stabilized and isolated as sodium salts and methyl ester. Nodulisporic acid B is 100-fold less active than nodulisporic acid A against fleas. The isolation, structure elucidation, and biological activities of these compounds are described.
1063Biosynthesis of nodulisporic acid A: precursor studies. Byrne KM, Smith SK, Ondeyka JG. J Am Chem Soc. 2002 Jun 19;124(24):7055-60.Nodulisporic acid A (NAA) is an indole-diterpene natural product produced by an indeterminate species of the endophytic fungus Nodulisporium. NAA (Figure 1) is structurally related to the paspaline class of fungal metabolites. The biosynthetic origin proposed for these alkaloids involves the acetate/mevalonic acid pathway leading to geranylgeranyl pyrophosphate (GGPP). GGPP is then proposed to condense with tryptophan to form the basic indole-diterpene core. A washed cell procedure was devised to incorporate labeled precursors into NAA by a mutant Nodulisporium culture designated MF6244. Incorporation of 2-(13)C-acetate and 2-(13)C-mevalonolactone into NAA was found to occur in the classical mevalonic acid pattern. In addition to the four mevalonic acid units that form the eastern side of the molecule, three additional isoprenylations occur to form the western and southern regions of NAA. Contrary to published reports on related compounds, incubations of Nodulisporium MF6244 with (14)C- and (13)C-tryptophan showed no incorporation of label into NAA. However, high levels of incorporation into NAA were obtained with known tryptophan precursors (14)C-, (13)C-, and (15)N-anthranilic acid and (14)C- and (13)C-ribose. A novel pathway for the biosynthesis of NAA is presented.
1065Metabolites of Dactylaria lutea. The structures of dactylariol and the antiprotozoal antibiotic dactylarin. Becker AM, Rickards RW, Schmalzl KJ, Yick HC. J Antibiot (Tokyo). 1978 Apr;31(4):324-9.The metabolites of the predacious fungus Dactylaria lutea ROUTIEN include the anthraquinone macrosporin (2) and three hydroxylated 1,2,3,4-tetrahydro derivatives of this anthraquinone, altersolanol A (5), altersolanol B (4) and dactylariol (6). The structure and relative configuration of dactylariol are established from spectroscopic studies, and its absolute configuration is proposed as 1R, 2R, 3R by virtue of its co-occurrence with altersolanol B. Dactylarin, suggested by other authors to have the structure (1), is shown to be identical with altersolanol B (4).
1066Dactylarin, a new antiprotozoal antibiotic from Dactylaria lutea. Kettner M, Nemec P, Kovác S, Balanová J. J Antibiot (Tokyo). 1973 Nov;26(11):692-6. 
1067Dactylfungins, novel antifungal antibiotics produced by Dactylaria parvispora. Xaio J, Kumazawa S, Yoshikawa N, Mikawa T, Sato Y. J Antibiot (Tokyo). 1993 Jan;46(1):48-55.Novel antifungal antibiotics, designated as dactylfungins A (1) and B (3), were isolated from the culture broth of Dactylaria parvispora D500. Dactylfungins A and B were found to be new substances containing an alpha-pyrone and a gamma-pyrone ring, respectively, which conjoined with a polyalcohol moiety and a long side chain, based on NMR spectral analyses. The antibiotics were active against Candida pseudotropicalis and other fungi, with an MIC value at less than 10 micrograms/ml.
1080Biologically active secondary metabolites from fungi. 12.(1) oidiolactones A-F, labdane diterpene derivatives isolated from oidiodendron truncata. John M, Krohn K, Florke U, Aust HJ, Draeger S, Schulz B. J Nat Prod. 1999 Sep;62(9):1218-21.Two known (1 and 2) and four new (3-6) diterpenes named oidiolactones A-F, respectively, and the antibiotic cladosporin were isolated from the fungus Oidiodendron truncata. The structure determination was mainly based on 1D and 2D NMR spectroscopy. The structures of compound 4, displaying an equilibrium between open-chain and cyclized form, and of cladosporin were confirmed by X-ray analysis.
1081Tetranorditerpene lactones, potent antifungal antibiotics for human pathogenic yeasts, from a unique species of Oidiodendron. Hosoe T, Nozawa K, Lumley TC, Currah RS, Fukushima K, Takizawa K, Miyaji M, Kawai K. Chem Pharm Bull (Tokyo). 1999 Nov;47(11):1591-7.The culture filtrate of a fungus isolated from decaying Picea glauca wood and tentatively identified as Oidiodendron cf. truncatum showed strong antibiotic activity against the pathogenic yeast, Candida albicans. Four new tetranorditerpenoids, oidiodendrolides A (3), B (4), and C (5) and oidiodendronic acid (7) were isolated along with three known tetranorditerpenoids, LL-Z1271 alpha (= PR1387) (1), PR1388 (2), and acrostalidic acid (6), from rice fermented by the above fungus. The structures of oidiodendrolides A (3), B (4), and C (5) and oidiodendronic acid (7) were established on the basis of spectroscopic and chemical investigations. The antifungal activity of the above tetranorditerpenoids against the pathogenic yeasts, Candida albicans and Cryptococcus neoformans is discussed.
1082Cytokine production inhibitors produced by a fungus, Oidiodendron griseum. Ichikawa K, Hirai H, Ishiguro M, Kambara T, Kato Y, Kim YJ, Kojima Y, Matsunaga Y, Nishida H, Shiomi Y, Yoshikawa N, Huang LH, Kojima N. J Antibiot (Tokyo). 2001 Sep;54(9):697-702.A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.
1083Fermentation, isolation and characterization of antibiotic PR-1350. Andersen NR, Lorck HO, Rasmussen PR. J Antibiot (Tokyo). 1983 Jul;36(7):753-60.A number of strains of Oidiodendron truncatum was shown to produce a new antibiotic, PR-1350, which was isolated in the form of an amorphous powder either directly or via a crystalline monomethanolate, PR-1381, which in solution is reconverted to the parent compound. The antibiotic inhibits a broad spectrum of Gram-positive and Gram-negative bacteria in vitro, and has been shown to be active against P-388 lymphocytic leukemia in mice. Biosynthetic considerations based on the results of [1-13C]acetate incorporation indicate that the antibiotic is a diterpene of the clerodane type.
1088Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes.Nam KS, Jo YS, Kim YH, Hyun JW, Kim HW. Life Sci. 2001 Jun 1;69(2):229-37.Paecilomyces tenuipes is one of the famous Chinese medicinal entomopathogenic fungi that parasites in the lavae of silkworm. Two cytotoxic components were isolated from methanolic extract of the carpophores of this fungus that was cultivated artificially. Spectral analyses of the cytotoxic components showed that they were known ergosterol peroxide (5alpha,8alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3beta-ol) and acetoxyscirpenediol (4beta-acetoxyscirpene-3alpha,15-diol) that were isolated for the first time from this fungus. The 50% inhibitory concentrations (IC50) of ergosterol peroxide against human gastric tumor cell line (SNU-1), human hepatoma cell line (SNU-354), human colorectal tumor cell line (SNU-C4) and murine sarcoma-180 were 18.7, 158.2, 84.6 and 74.1 microM, respectively. The IC50 values of acetoxyscirpenediol against SNU-1, SNU-C4, SNU-354 and sarcoma-180 were 1.2,4.0, 2.2 and 1.9 microM, respectively. Cytotoxic activities of acetoxyscirpenediol were about 4.0-6.6 times stronger than those of cisplatin which is currently used clinically for cancer patients.
1089Toxinogenic moulds in silage. V. - Production of byssochlamic acid in liquid medium with by Byssochlamys nivea Westling, Byssochlamys fulva Olliver and Smith and Paecilomyces varioti Bainier isolated in forages (author's transl)] Escoula L. Ann Rech Vet. 1975;6(3):311-4.The toxinogenesis of 10 strains of Byssochlamys nivea, 4 of Byssochlamys fulva and 8 of Paecilomyces varioti is studied in Czapek's enriched liquid medium (8 p. 1000 glucose + 2p. 1000 yeast extract) at 26 degrees C. 60 p. 100 of Byssochlamys nivea filtrates, 100 p. 100 of Byssochlamys fulva filtrates and 37 p. 100 of Paecilomyces varioti filtrates contain byssochlamic acid after 60 days of culture at 26 degrees C. The concentrations observed vary from 40 to 540 p.p.m. In these moulds, patuline-production ability has also been tested (Escoula, 1975 c). There seems to be no relation between the production of patuline and of byssochlamic acid in these three species.
1090Paecilotoxin production in clinical or terrestrial isolates of Paecilomyces lilacinus strains. Mikami Y, Yazawa K, Fukushima K, Arai T, Udagawa S, Samson RA. Mycopathologia. 1989 Dec;108(3):195-9.The production of paecilotoxin from various isolates of Paecilomyces lilacinus was studied using three different media and high performance liquid chromatography (HPLC). Alkaline medium was found to be suitable for the production of the toxins. Among 20 strains tested, 19 including four clinical isolates were found to produce the toxins. Production patterns of paecilotoxins were very similar in each strain and the main toxins were A and B.
1091The interaction between additives, yeast and patulin production in grass silage. Dutton MF, Westlake K, Anderson MS. Mycopathologia. 1984 Aug 30;87(1-2):29-33.Both laboratory-prepared and sterile farm silage was found to support growth of Paecilomyces sp. and patulin production. The formation of patulin was affected by the levels of yeast present in the silage, and it was found that there was an inverse relationship between yeast population levels and patulin concentration. The commercial silage additive, "Sylade' had a greater lethal effect on yeast and fungi than "Add F', the latter allowing the formation of patulin by Paecilomyces sp. in the silage.
1092 Patulin production by Paecilomyces species isolated from silage in the United Kingdom. Hacking A, Rosser WR. J Sci Food Agric. 1981 Jun;32(6):620-3 
1093 Variotin, a new antifungal antibiotic, produced by Paecilomyces varioti Bainier var. antibioticus. Yonehara H, Takeuchi S, Umezawa H, Sumiki Y. J. Antibiotics, Ser. A, Tokyo 1959 May;12(3):109-10 
1129UV-Guided isolation of verrucines A and B, novel quinazolines from penicillium verrucosum structurally related to anacine from Penicillium aurantiogriseum. Larsen TO, Franzyk H, Jensen SR. J Nat Prod. 1999 Nov;62(11):1578-80.Two novel quinazolines, verrucines A (1) and B (2), have been isolated as a major and a minor metabolite, respectively, of Penicillium verrucosum. Both are condensates of one mole each of anthranilic acid, phenylalanine, and glutamine. The structures were elucidated by spectroscopic methods, and the two compounds were found to be epimers. The spectroscopic data for the ostensible benzodiazepine anacine reported from Penicillium aurantiogriseum, composed of one mole each of anthranilic acid, leucine, and glutamine, appeared very similar to those of 1. Therefore, a revised quinazoline structure for anacine is proposed.
1130UV-guided screening of benzodiazepine producing species in Penicillium. Ostenfeld Larsen T, Frydenvang K, Christian Frisvad J. Biochem Syst Ecol. 2000 Nov 1;28(9):881-886.The benzodiazepine sclerotigenin (auranthine B) recently described as a metabolite of Penicillium sclerotigenum, has been isolated as the major metabolite from an isolate of P. commune. The structure of sclerotigenin was established by a single-crystal X-ray diffraction study and by NMR spectroscopy. UV-guided screening for benzodiazepine production by other penicillia revealed that sclerotigenin was also produced by isolates of P. clavigerum, P. lanosum, P. melanoconidium, P. sclerotigenum and P. verrucosum. Sclerotigenin was detected both intra- and extracellularly. Apparently, P. aurantiogriseum is the only auranthine producing species in genus Penicillium.
1131Production of brefeldin-A. McCloud TG, Burns MP, Majadly FD, Muschik GM, Miller DA, Poole KK, Roach JM, Ross JT, Lebherz WB 3rd. J Ind Microbiol. 1995 Jul;15(1):5-9.Fermentation conditions are described for the production of the antitumor antibiotic 7-(S)-brefeldin-A (brefeldin-A) in liquid culture by Eupenicillium brefeldianum, (B.Dodge) Stolk and Scott, ATCC 58665. An analytical hplc method was developed which allowed rapid quantitation of the compound during fermentation. A kilogram of brefeldin-A was isolated from a fermentation at the 6800-liter scale.
1132 The antibiotic PSX-1 produced by Penicillium stipitatum is identical with botryodiplodin. Fuska J, Proksa B, Uhrín D. Folia Microbiol (Praha). 1988;33(3):238-40.Antibiotic PSX-1 exhibiting antitumour activity, formerly isolated from the filtrate of a culture of Penicillium stipitatum, was shown to be identical with botryodiplodin.
1133Classification of terverticillate penicillia based on profiles of mycotoxins and other secondary metabolites. Frisvad JC, Filtenborg O. Appl Environ Microbiol. 1983 Dec;46(6):1301-10.Strains of available terverticillate penicillium species and varieties were analyzed for profiles of known mycotoxins and other secondary metabolites produced on Czapek yeast autolysate agar (intracellular metabolites) and yeast extract-sucrose agar (extracellular metabolites) by using simple thin-layer chromatography screening techniques. These strains (2,473 in all) could be classified into 29 groups based on profiles of secondary metabolites. Most of these profiles of secondary metabolites were distinct, containing several biosynthetically different mycotoxins and unknown metabolites characterized by distinct colors and retardation factors on thin-layer chromatography plates. Some species (P. italicum and P. atramentosum) only produced one or two metabolites by the simple screening methods. The 29 groups based on profiles of secondary metabolites were known species or subgroups thereof. These species and subgroups were independently identifiable by using morphological and physiological criteria. The species accepted, the number of isolates in each species investigated, and the mycotoxins they produced were: P. atramentosum, 4; P. aurantiogriseum, 510 (group I: penicillic acid and S-toxin and group II: penicillic acid, penitrem A [low frequency], terrestric acid [low frequency], viomellein, and xanthomegnin); P. brevicompactum, 81 (brevianamid A and mycophenolic acid); P. camembertii group I, 38, and group II, 114 (cyclopiazonic acid); P. chrysogenum, 87 (penicillin, roquefortine C, and PR-toxin); P. claviforme, 4 (patulin and roquefortine C); P. clavigerum, 4 (penitrem A); P. concentricum group I, 10 (griseofulvin and roquefortine C), and group II, 3 (patulin and roquefortine C); P. crustosum, 123 (penitrem A, roquefortine C, and terrestric acid); P. echinulatum, 13; P. expansum, 91 (citrinin, patulin, and roquefortine C); P. granulatum, 6 (patulin, penitrem A, and roquefortine C [traces]); P. griseofulvum, 21 (cyclopiazonic acid, griseofulvin, patulin, and roquefortine C); P. hirsutum, 100 (group I: terrestric acid; group II: citrinin, penicillic acid , roquefortine C, and terrestric acid; and group III: roquefortine C and terrestric acid), P. hirsutum group IV, 2 (chaetoglobosin C); P. isariiforme, 1; P. italicum, 41; P. mali, 104; P. roquefortii, 78 (group I: mycophenolic acid, PR-toxin, and roquefortine C and group II: mycophenolic acid, patulin, penicillic acid [low frequency], and roquefortine C); P. viridicatum group I, 634 (brevianamid A [low frequency], penicillic acid, viomellein, and xanthomegnin), P. viridicatum group II and III, 494 (citrinin and ochratoxin A), P. viridicatum group IV, 12 (griseofulvin and viridicatumtoxin). It is proposed that profiles of secondary metabolites be strongly emphasized in any future revision of the penicillia.
1134Mycotoxin production by Penicillium expansum on blackcurrant and cherry juice. Larsen TO, Frisvad JC, Ravn G, Skaaning T. Food Addit Contam. 1998 Aug-Sep;15(6):671-5.The production of mycotoxins and other secondary metabolites by Penicillium expansum on blackcurrant and cherry juice has been studied at 10 degrees C and 25 degrees C under storage imitated conditions. P. expansum was able to synthesize extracellular patulin under all conditions, and together with extracellular chaetoglobosin A when unlimited oxygen was available. Patulin, the chaetoglobosins A and C, the communesins A and B and the expansolides A and B could be detected intracellularly depending on the conditions. The metabolites were detected using thin-layer chromatography and high-performance liquid chromatography with diode array detection by comparison to standards. A method to detect the expansolides A and B by TLC was developed.
1135Taxonomy of Penicillium nalgiovense isolates from mould-fermented sausages. Andersen SJ. Antonie Van Leeuwenhoek. 1995 Aug;68(2):165-71.A large number of Penicillium nalgiovense isolates from mould fermented sausages and the ex type culture were examined for characters of morphology, physiology and production of secondary metabolites. To separate biotypes within the P. nalgiovense species, the data obtained were evaluated using multivariate statistical methods. The macromorphological characters of the ex type culture and isolates from meat products appeared to be distinctive. The ex type culture is characterized by a brown reverse on both Czapek yeast extract and malt extract agar while the isolates from meat products have a yellow to orange reverse. Proteolytic and/or lipolytic activity was demonstrated by 75% of the examined cultures and all of them demonstrated ability to utilize lactate as sole carbon source. Growth on creatine sucrose agar was very inhibited and acid production was absent or very weak. TLC analysis showed production of three unknown secondary metabolites that constituted the characteristic profile. HPLC analysis showed production of only three known secondary metabolites; chrysogine (96%), nalgiolaxin and nalgiovensin (9%). The ex type culture produced nalgiolaxin and nalgiovensin but not chrysogine. The chemometric evaluation showed that P. nalgiovense isolates from meat products from a homogenous species, which can not be divided into biotypes. The only indication of grouping, beside a separation of the ex type culture, was related to the conidium colour (white, turquoise or grey green). The examined P. nalgiovense isolates showed some resemblance (morphologically and chemically) to P. chrysogenum.
1136Secondary metabolites characteristic of Penicillium citrinum, Penicillium steckii and related species. Malmstrom J, Christophersen C, Frisvad JC. Phytochemistry. 2000 Jun;54(3):301-9.Two new carboxylic acids, tanzawaic acid E (1) and F (2) in addition to the unknown benzopyran 3,7-dimethyl-1,8-dihydroxy-6-methoxy-isochroman (3), and the known mycotoxin 3,7-dimethyl-8-hydroxy-6-methoxyisochroman (4) were produced by a marine-derived strain of Penicillium steckii isolated from an unidentified tunicate. The carboxylic acids and the benzopyran were identified on the basis of mass spectrometry, and one and two dimensional NMR spectroscopic techniques. The structures 1 and 2 resemble tanzawaic acid A-D, previously isolated from Penicillium citrinum. Screening of isolates of species related to P. citrinum and P. steckii showed that P. citrinum (25 isolates) consistently produced citrinin and tanzawaic acid A, P. steckii (18 isolates) produced isochroman toxins (except 2) and tanzawaic acid E, P. sizovae consistently produced tanzawaic acid A, P. corylophilum (10 isolates) produced citreoisocoumarinol and P. sumatrense (15 isolates) always produced curvularin.
1137Toxicity of citreoviridin. Nishie K, Cole RJ, Dorner JW. Res Commun Chem Pathol Pharmacol. 1988 Jan;59(1):31-52.The mycotoxin citreoviridin (CIT) isolated from Penicillium citreoviride was studied to elucidate the mechanism of its toxic actions. In CF#1 mice, near lethal doses of CIT decreased motor activities, body temperature and had cataleptic effects. Male mice appeared to be more susceptible to CIT and had lower subcutaneous (sc) LD50 values and longer CIT-induced hypothermia and hypokinesia. In CIT-treated mice the weights and histology of liver, kidneys and adrenals were normal one week after sc treatment, except for the increased adrenal weights in female mice. Single doses of CIT (sc), given on either day 4 or 5 of pregnancy (perinidation period), had no adverse effect on the rates of pregnancy, implantation of ova and embryonal resorptions in those mice examined on day 12 of pregnancy. CIT (40 mg/kg ip) produced a brief electro-encephalographic (EEG) activation, cardiac sinus arrhythmias and tachypnea in the rabbit. Intravenous (iv) lethal doses of CIT (greater than or equal to 5 mg/kg) caused an EEG activation followed by high voltage delta waves, increased the T wave in the electrocardiogram (ECG) and depressed the respiratory amplitude. The death caused by iv CIT started with the respiratory arrest, followed by isoelectric EEG and ECG was the last to stop. In urethane-anesthetized rabbits CIT decreased the blood pressure, and in succession it lowered, flattened and inverted the T wave of ECG suggesting heart ischemia. These observations indicated that the toxic effects of CIT resulted from respiratory and cardiovascular failures (apnea, delta EEG waves, sinus arrhythmia, hypotension) leading to central nervous system depression due to systemic hypoxia
1138 Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum. Brown AG, Smale TC, King TJ, Hasenkamp R, Thompson RH. J Chem Soc [Perkin 1]. 1976;(11):1165-70. 
1139 Fatty acid, lipid and cyanein production by Penicillium cyaneum. Koman V, Betina V, Baráth Z. Arch Mikrobiol. 1969;65(2):172-80. 
1140 Production of cyanein by Penicillium simplicissimum. Betina V, Fuska J, Kjaer A, Kutkova M, Nemec P, Shapiro RH. J Antibiot (Tokyo). 1966 May;19(3):115-7. 
1141Mutagenicity and antibacterial activity of mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum. Stark AA, Townsend JM, Wogan GN, Demain AL, Manmade A, Ghosh AC. J Environ Pathol Toxicol. 1978 Nov-Dec;2(2):313-24.Twelve mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum in solid-state fermentation on grains were purified and tested for mutagenicity and antibacterial activity in Salmonella/mammalian microsome assays. The mutations studied were reversions of histidine auxotrophs to prototrophy in strains TA98 and TA100 and forward mutations to 8-azaguanine resistance (8AGR) in strain TM677. Rubroskyrin, (+)rugulosin, lumiluteoskyrin [a photoproduct of (-)luteoskyrin], and simatoxin [a new water-soluble metabolite of unknown structure] induced 8AGR mutations in strain TM677 but not histidine reversions in strains TA98 and TA100. Mutagenic potency was reduced by rat-liver microsomes. The carcinogens (-)luteoskyrin and cyclochlorotine were antibacterial but not mutagenic. (+)Rugulosin, rubroskyrin, lumiluteoskyrin, and high concentrations of simotoxin were also antibacterial. Antibacterial activity but not mutagenicity was observed with pibasterol and skyrin. Chrysophanol, islandicin, iridoskyrin, and emodin were inactive as mutagens or as antibacterial agents.
1142Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. I. Screening, taxonomy, fermentation, isolation and biological activity. Kuno F, Otoguro K, Shiomi K, Iwai Y, Omura S. J Antibiot (Tokyo). 1996 Aug;49(8):742-7.An in vitro screening method for selective acetylcholinesterase (AChE) inhibitors was established. Inhibitory activity of AChE and butyrylcholinesterase (BuChE) was measured and the culture broths of microorganisms that showed selective inhibition against AChE were characterized. By using this method, a strain producing the novel and selective inhibitors of AChE, arisugacins A and B, was picked out among over seven thousand microorganisms tested. Arisugacins were obtained as white powders from the culture broth together with three known compounds, territrems B and C and cyclopenin that also showed selective inhibition against AChE. Arisugacins and territrems are members of the meroterpenoid compounds. They showed potent inhibitory activities against AChE with IC50 values in range of 1.0 approximately 25.8 nM. Furthermore, they showed greater than 2,000-fold more potent inhibition against AChE than BuChE.
1143Verrucofortine, a major metabolite of Penicillium verrucosum var. cyclopium, the fungus that produces the mycotoxin verrucosidin. Hodge RP, Harris CM, Harris TM. J Nat Prod. 1988 Jan-Feb;51(1):66-73.Verrucofortine [8], an alkaloid derived from tryptophan and leucine, has been isolated from the fungus Penicillium verrucosum var. cyclopium. The structure and absolute configuration have been established by a combination of spectroscopic and chemical techniques. Its structure is unrelated to that of other major metabolite of the organism, the highly toxic pyrone-type polyketide verrucosidin [1], which was previously reported to be a tremorgen. A second novel metabolite, normethylverrucosidin [3], has also been isolated and identified. Small quantities of several other secondary metabolites, ergosterol, cyclopenin [4], cyclopenol [5], and 3-O-methylviridicatin [6], were isolated. They are known fungal metabolites but had not previously been obtained from this fungus. Studies of verrucofortine toxicity in mice showed no apparent toxic effects at doses as high at 160 mg/kg ip.
1144Immunosuppressive properties of the antibiotics cytostipin and vermiculine. Horáková L, Nouza K, Pospísil M, Konopásková E, Klapácová J, Fuska J. Folia Biol (Praha). 1980;26(5):312-26.The properties of two antibiotics, cytostipin isolated from Penicillium stipitatum and vermiculine isolated from Penicillium vermiculatum, were examined in two systems for a rapid screening of current immunosuppressive agents [nucleolar test determining the degree of RNA synthesis in nucleoli of individual lymphocyte populations, and the reactivity of mouse lymphocytes to "T" (PHA) and "B" (LPS) mitogens]. Both antibiotics, distinctly suppressed the increase in number of "active" lymphocytes with compact nucleoli in the popliteal lymph node activated by SRBC. Incorporation of 3H-uridine into PHA-stimulated "T" lymphocytes was suppressed by both antibiotics, incorporation into LPS-stimulated "B" lymphocytes was inhibited by cytostipin but stimulated by vermiculine. The antibiotics were also tested in another two "classic" immune systems, the Jerne test and the GVH reaction. Both antibiotics in doses markedly inhibitory for GVH reaction did not suppress but significantly increased the number of the haemolytic plaques in spleens of SRBC-immunized mice.
1145Toxin-producing species of Penicillium and the development of mycotoxins in must and homemade wine. Möller T, Akerstrand K, Massoud T. Nat Toxins. 1997;5(2):86-9.A number of penicillium strains belonging to the species Penicillium roqueforti, P. crustosum, P. paneum Frisvad, and P. chrysogenum were analyzed for their ability to produce the mycotoxins isofumigaclavine A, isofumigaclavine B, festuclavine, roquefortine C, and PR toxin when cultured on three different media. Some of the strongest mycotoxin-producing strains were later inoculated into samples of must (grape juice) before and after wine fermentation. After incubation at 25 degrees C for 1 and 2 weeks it was found that all except one of the penicillium strains were able to produce one or more of the toxins analyzed. However, the types of toxins as well as toxin concentrations varied a great deal, depending on culturing medium or culturing time. The media containing yeast extract normally gave higher toxin levels. From the wine experiments it was shown that isofumigaclavine A can be formed under certain circumstances in must and wine. A qualitative High Performance Liquid Chromatography (HPLC) method for simultaneous determination of isofumigaclavines A and B, roquefortine C, and PR toxin was also developed.
1146An intermediary role for the tremorgenic mycotoxin TR-2 in the biosynthesis of verruculogen. Willingale J, Perera KP, Mantle PG. Biochem J. 1983 Sep 15;214(3):991-3.14C-Labelled compound TR-2, a tremorgenic mycotoxin, was administered to Penicillium raistrickii in submerged fermentation. Half of the added radiolabel was taken up by the fungus during the 60 h incubation period and the secondary metabolites subsequently isolated, principally verruculogen but also fumitremorgin B, were found to be radiolabelled. The efficiency of biosynthetic incorporation of TR-2 into verruculogen within the mycelium was at least 35%, demonstrating for the first time an intermediary role for TR-2. Fumitremorgin B was also TR-2-derived but may not be an important intermediate in verruculogen biosynthesis.
1147Penicillin G production by immobilized whole cells of Penicillium chrysogenum. Morikawa Y, Karube I, Suzuki S. Biotechnol Bioeng. 1979 Feb;21(2):261-70.Penicillium chrysogenum was immobilized in polyacrylamide gel prepared from 5% acrylamide monomers (85% acrylamide and 15% N,N'-methylene bisacrylamide). Penicillin produced from glucose by the immobilized mycelium was 17% of that produced by washed mycelium. However, the activity of penicillin production of the washed mycelium decreased with repeated use. On the other hand, the activity of the immobilized mycelium increased initially and decreased gradually with repeated use. The rate of oxygen uptake of the immobilized mycelium was about 30% of that of the washed mycelium. The immobilized mycelium required oxygen for the production of penicillin.
1148Nephrotoxicity of Penicillium aurantiogriseum, a possible factor in the aetiology of Balkan endemic nephropathy. Yeulet SE, Mantle PG, Rudge MS, Greig JB. Mycopathologia. 1988 Apr;102(1):21-30.Water-soluble components of a nephrotoxic isolate of Penicillium aurantiogriseum have been fractionated by sequential ion-exchange, size-exclusion gel filtration, reverse-phase silica chromatography and HPLC. Nephrotoxicity in the rat was confined to a size-exclusion fraction approximating to 1,500 daltons, which also inhibited DNA synthesis in cultured kidney cells. The more sensitive in vitro assay allowed toxicity to be followed to a sub-fraction from gradient-elution HPLC which in further HPLC resolved into a small group of glycopeptides. Recent Yugoslavian P. aurantiogriseum isolates, from a village in which the idiopathic human disease Balkan Nephropathy is hyperendemic, elicited a similar nephropathology and were acutely cytotoxic, reinforcing a need to regard this novel Penicillium nephrotoxin as a potential factor in human nephropathy.
1149Penicillium rubrum and Penicillium biforme, new sources of rugulovasines A and B. Dorner JW, Cole RJ, Hill R, Wicklow D, Cox RH. Appl Environ Microbiol. 1980 Sep;40(3):685-7.An isolate of Penicillium biforme Thom produced rugulovasines A and B. An isolate of Penicillium rubrum Stoll produced rugulovasines A and B and also chlororugulovasines A and B. Both fungi represent new sources of the rugulovasines.
1150Some newly discovered mycotoxins. Steyn PS, Jemmali M. Ann Nutr Aliment. 1977;31(4-6):651-62.The discovery of the aflatoxins in 1960 has taken place in the present era of the intense awareness of the importance of environmental contaminants. It has dramatically influenced subsequent fungal research with the resulting rapid increase in the number of publications describing mycological, chemical, toxicological and epidemiological aspects of mycotoxins. In this contribution results will be discussed which were published only subsequent to 1970. In this period the importance of several new classes of mycotoxins was realized, e.g. the toxic cytochalasins and the tremorgens. The potential role of highly oxygenated metabolites in mycotoxicosis was emphasized by the establishment of secalonic acids A and D. emodin, moniliformin, altenuisiol alternariol and austdiol as toxins. The structure of viridicatumtoxin, C30H31NO11, a metabolite produced by Penicillium viridicatum will be described. It is a novel compound, structurally related to the tetracyclines. The characterization of several mycotoxins from other toxigenic fungi will be reported
1151Studies on synergisidin. Jinnouchi H, Yagishita K. Jpn J Antibiot. 1981 Jan;34(1):51-60.Penicillium sp. No. Y-11930 was isolated from soil sample collected at Shimouma, Setagaya, Tokyo in
September 1978. Synergisidin produced by the strain was obtained with high yield in starch-corn steep liquor medium, extracted with ethyl acetate at pH 5.0 and crystallized from ethyl acetate after decolorization with active charcoal. The antibacterial activities of synergisidin against Gram-positive and Gram-negative bacteria and Mycobacterium were almost nothing but synergisidin showed weak activities against eumycetes with MICs of 6.25-100 microgram/ml. However, synergidisin was confirmed and discovered to show 30-125-fold strong synergistic effects against Candida sp. in particular with addition to extremely small quantities of imidazole antimycotics such as econazole, miconazole and clotrimazole. The acute toxicity was LD50 smaller than or equal to 250 mg/kg in mice (i.p.). the morphological degenerative effect on HeLA cells was observed in concentrations of more than 0.122 microgram/ml. The chemical structure of synergisidin was estimated as 7, 16-dihydroxy-2-methyl-4-oxo-3-oxabicyclo [10. 3. 1] hexadeca-5, 10-diene or 2, 15-dihydroxy-7-methyl-5-oxo-6-oxabicyclo (11. 3. 0] hexadeca-3, 11-diene (the same structure as decumbin, brefeldin A and ascotoxin) from various physiochemical properties but later, comparison with brefeldin A and ascotoxin revealed that synergisidin was identical with those.
1152 Metabolites of the xanthocillin(Brevicid)-producing mutant of Penicillium notatum Westl] Pfeifer S, Bar H, Zarnack J. Pharmazie. 1972 Aug;27(8):536-42. German. 
1170Structure of the host-specific toxins produced by the fungal pathogen Periconia circinata. Macko V, Stimmel MB, Wolpert TJ, Dunkle LD, Acklin W, Bänteli R, Jaun B, Arigoni D. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9574-8.Four metabolites named peritoxins A and B and periconins A and B have been isolated together with the known metabolite circinatin from culture filtrates of the fungal pathogen Periconia circinata. Peritoxins A and B, which correspond to the P. circinata toxins Ia and IIa partially characterized in previous work, are selectively toxic to genotypes of Sorghum bicolor susceptible to the pathogen, whereas periconins A and B are biologically inactive. Combination of instrumental analysis and chemical degradation has led to structural assignments for each of the four compounds; only the configuration at some of the chiral centers remains undefined. Structural comparison suggests a precursor role for circinatin in the formation of the peritoxins and the periconins.
1171Studies on WF-3161, a new antitumor antibiotic. Umehara K, Nakahara K, Kiyoto S, Iwami M, Okamoto M, Tanaka H, Kohsaka M, Aoki H, Imanaka H. J Antibiot (Tokyo). 1983 May;36(5):478-83.WF-3161 is an antitumor antibiotic produced by a strain of fungus, Petriella guttulata. The antibiotic was purified by solvent extraction and a combination of silica gel and reverse phase column chromatography. The chemical structure of the antibiotic (C31H44N4O6, mp 181-183 degrees C) was found to be a cyclic tetrapeptide consisting of phenylalanine, leucine, pipecolinic acid and 2-amino-8-oxo-9,10-epoxydecanoic acid. WF-3161 inhibited the growth of Trichophyton asteroides. It prolonged survival period of mice bearing leukemia P-388 with a high therapeutic index.
1172Ascopyrone P, a novel antibacterial derived from fungi. Thomas LV, Yu S, Ingram RE, Refdahl C, Elsser D, Delves-Broughton J. J Appl Microbiol. 2002;93(4):697-705.AIMS: To assess the antimicrobial efficacy of ascopyrone P (APP), a secondary metabolite formed by the fungi Anthracobia melaloma, Plicaria anthracina, Plic. leiocarpa and Peziza petersi belonging to the order Pezizales. METHODS AND RESULTS: In vitro testing using a well diffusion procedure showed that APP at a high concentration (approximately 5%) inhibited the growth of Gram-positive and Gram-negative bacteria. Using an automated microbiology reader, growth curve analysis showed that 2000-4000 mg l(-1) APP caused total or significant bacterial inhibition after incubation for 24 h at 30 degrees C. Against certain yeast strains, 1000- 2000 mg l(-1) APP enhanced growth, although at higher concentrations inhibition of some yeasts was observed. Clostridium and fungal strains were not sensitive to 2000 mg l(-1) APP. No significant cidal effect was observed after 2 h against Listeria monocytogenes or Escherichia coli. Results were identical whether the APP samples tested had been produced enzymatically or chemically. CONCLUSIONS: At a level of 2000 mg l(-1), APP demonstrated growth inhibitory activity against a broad range of bacteria, but not yeasts or moulds. SIGNIFICANCE AND IMPACT OF THE STUDY: A possible application for this novel natural antimicrobial is in food preservation, to control the growth of Gram-negative and Gram-positive bacteria in raw and cooked foods. Effective dosage levels would be 500-4000 mg kg(-1), depending on food type. The efficacy, organoleptic and safety aspects of this compound in food still need to be assessed.
1173Purification, antitumor activity, and structural characterization of beta-1,3-glucan from Peziza vesiculosa. Mimura H, Ohno N, Suzuki I, Yadomae T. Chem Pharm Bull (Tokyo). 1985 Nov;33(11):5096-9 
1203Cytochalasin W, a new 24-oxa[14]cytochalasan from Phoma exigua var. heteromorpha. Evidente A, Capasso R, Vurro M, Bottalico A. Nat Toxins. 1996;4(2):53-7.A further cytochalasin was isolated from liquid culture filtrates of Phoma exigua var. heteromorpha together with cytochalasins U and V and other well-known cytochalasins. The metabolite, named cytochalasin W, was characterized by spectroscopic and chemical methods as a new 24-oxa[14]cytochalasan, bearing a formyl group on the macrocyclic ring. Cytochalasin W showed toxic activity in the brine shrimp assay.
1208Fungitoxic activity of some cytochalasins and their derivatives on Phytophthora species. Evidente A, Cristinzio G, Capasso R, Andolfi A. Nat Toxins. 1997;5(6):228-33.The activity of cytochalasin B was tested on 8 Phytophthora species, while the same toxin, some of its derivatives and natural analogues, namely cytochalasin F and deoxaphomin, were assayed at 2 x 10(-5) - 2 x 10(-4) M on the most sensitive species, P. cactorum. A significant inhibitory activity on P. cactorum was shown by cytochalasin B, its 7-monoacetyl derivative, and deoxaphomin. The hydroxy group at C-20 and the conformational freedom of the macrocyclic ring proved to be important structural features for this activity. The 7-hydroxy group at C-7 appeared to have no influence on this toxicity, while a size reduction associated with the carbocyclic nature of the macrocycle seems to lightly increase the activity. The 7-O-acetylcytochalasin B showed selective toxic activity on P. cactorum at the tested concentration, thus suggesting a possible use as a fungicide for this compound.
1209Cloning, expression, and biological activity of recombinant alpha-cinnamomin: toxicity to cranberry and other plant species. Ivanova DG, Sarkar HK, Singh BR. J Nat Toxins. 2002 May;11(2):95-102.Elicitins produced by the pathogenic fungi Phytophthora are known to exhibit The elicitin cinnamomin is of nonspecific toxicity to different solanaceous plant species. particular interest for its potential role in the hypersensitive-like cell death and in the biological response of cranberry plants to the fungal pathogen Phytophthora cinnamomi. In order to understand the biochemical steps of the Phytophthora root rot disease in cranberry, we investigated the alpha-cinnamomin-induced plant responses. Toxicity of alpha-cinnamomin, which shows a high degree of sequence homology to the alpha-elicitin group, was tested on Vaccinum macrocarpon, Nicotiana tabacum, Capsicum annuum, Lycopersicon esculentum, Lactuca sativa, and Phaseolus vulgaris plants. Gene corresponding to alpha-cinnamomin gene fused with maltose binding protein gene, was cloned into a pMALTEV expression vector, which was transformed into E. coli cells. Cells containing alpha-cinnamomin clones were cultured and extracted protein was purified on a maltose binding protein affinity column. Biological activity of alpha-cinnamomin fusion protein was examined on propagated plants and cuttings. In cranberry plants treated with cinnamomin necrotic hypersensitive-like response in the proximal areas of the leaf lamina of lower plant leaves was observed after 48-72 hr of incubation. Limited leaf necrosis observed days after application of low amounts of recombinant cinnamomin directly on the leaves of other plants indicates that the recombinant protein
1213Metal complexes of sporidesmin D and dimethylgliotoxin, investigated by electrospray ionisation mass spectrometry. Woodcock JC, Henderson W, Miles CO, Nicholson BK. J Inorg Biochem. 2001 Apr;84(3-4):225-32.Electrospray ionisation mass spectrometry (ES-MS) has been used to probe the coordination chemistry of metabolites such as sporidesmin D (spdD), found in the saprophytic fungus Pithomyces chartarum, and the related bisdethiobis(methylthio)gliotoxin (dimethylgliotoxin, Megtx). SpdD forms complexes of the type [spdD+M(MeCN)] and [2spdD+M]+ (M=Cu, Ag) and, at higher cone voltages, [spdD+M]+. The bis(ligand) ion [2spdD+M]+ was observed at very high cone voltages, indicating it has appreciable stability; the proposed structure of this species has a four-coordinate metal ion with two bidentate spdD ligands, coordinated through their SMe groups. 1H NMR titrations of spdD with K+, Ag+ and Cu+ provided additional evidence for complex formation with the soft metals. SpdD forms only relatively weak complexes with Zn2+, Cd2+, Co2+ and Mn2+, in keeping with the known reduced tendency of these metals to form stable thioether complexes. ES-MS studies of Megtx showed similar results to spdD, with stable adducts formed with Cu+ and Ag+ ions. The X-ray crystal structure of spdD is also reported.
1214Interaction of sporidesmin, a mycotoxin from Pithomyces chartarum, with lipid bilayers. Upreti GC, Jain MK. Biosci Rep. 1993 Aug;13(4):233-43.Sporidesmin, a mycotoxin from Pithomyces chartarum is a hydrophobic molecule. It can therefore be easily incorporated in the cell membrane, where it is likely to cause changes in the bilayer organization and the properties of membrane proteins. In order to understand the redox behaviour of sporidesmin in a hydrophobic environment, we have investigated the effects of oxidized and reduced sporidesmin on the phase transition properties of bilayers and on the susceptibility of bilayers to pancreatic phospholipase A2 (PLA2). The changes induced by sporidesmin in the thermotropic phase transition profiles of dimyristoyl-sn-3-phosphatidyl choline (DMPC) bilayers were similar to those caused by solutes known to localize in the glycerol-backbone region of the lipid bilayer, suggesting a similar localization for oxidized and reduced sporidesmin. Neither form of toxin disrupt the bilayer or membrane organization even at relatively high mole fractions. At concentrations < 10 mole% both forms partitioned equally well in the gel and liquid-crystalline phases, whereas at higher concentrations (approximately 30 mole%) reduced sporidesmin is preferentially localized in the liquid-crystalline phase. These effects of sporidesmin on the phase properties of DMPC vesicles were also reported by the fluorescence behavior of 10-pyrenedecanoic acid (PDA). The effects of oxidized and reduced sporidesmins on PLA2 kinetics are consistent with their ability to perturb bilayer organisation.
1215Ecotoxinogenesis of Pithomyces chartarum. Le Bars J, Oswald E, Le Bars P, Bonnefoi M, Bezille P, Braun JP. Food Addit Contam. 1990;7 Suppl 1:S19-21.Facial eczema is a hepatogenous photosensitivity mycotoxicosis resulting from sporidesmin ingestion. The morphological characters of toxigenic strains of P. chartarum are reported and the effect of temperature on growth and mycotoxin production are studied. The temperature range for which there is an actual risk of toxin accumulation (20-25 degrees C) is much narrower than for an appreciable growth (5-30 degrees C).
1216Sporidesmin production and sporulation in Pithomyces chartarum. DiMenna ME, Campbell J, Mortimer PH. J Gen Microbiol. 1970 Apr;61(1):87-96. 
1217 Production of sporidesmin and sporidesmolides by Pithomyces chartarum. DONE J, MORTIMER PH, TAYLOR A, RUSSELL DW. J Gen Microbiol 1961 Oct;26:207-22. 
1225Auranticins A and B: two new depsidones from a mangrove isolate of the fungus Preussia aurantiaca. Poch GK, Gloer JB. J Nat Prod. 1991 Jan-Feb;54(1):213-7.Auranticins A and B, two new antimicrobial depsidones, have been obtained from a mangrove isolate of the fungus Preussia aurantiaca. The structures were determined through analysis of selective INEPT, decoupling, COSY, and NOESY experiments.
1250Three novel cytochalasins X, Y, and Z from Pseudeurotium zonatum. Feng Y, Blunt JW, Cole AL, Munro MH. J Nat Prod. 2002 Sep;65(9):1274-7.Fermentation of Pseudeurotium zonatum led to the isolation of the known cytochalasin G (1) and three new cytochalasins, X, Y, and Z (2-4). These four compounds are the only naturally occurring cytochalasins reported to date that contain an indole-substituted perhydroisoindol-1-one fused with an 11-membered macrocycle.
1251Pseurotin, a new metabolite of Pseudeurotium ovalis Stolk having an unusual hetero-spirocyclic system. Bloch P, Tamm C, Bollinger P, Petcher TJ, Weber HP. Helv Chim Acta. 1976 Jan 28;59(1):133-7. 
1254A32390A, a new biologically active metabolite. II. Isolation and structure. Marconi GG, Molloy BB, Nagarajan R, Martin JW, Deeter JB, Occolowitz JL. J Antibiot (Tokyo). 1978 Jan;31(1):27-32An inhibitor of dopamine-beta-hydroxylase, designated A32390A, was isolated from the culture broth of a Pyrenochaeta species. The inhibitor showed antimicrobial activity against fungi and gram-positive bacteria. Spectroscopic analysis and chemical degradation studies indicated that the structure was 1,6-di-O-(2-isocyano-3-methylcrotonyl)-D-mannitol.
1255Antibiotic activity of the pyrenocines. Sparace SA, Reeleder RD, Khanizadeh S. Can J Microbiol. 1987 Apr;33(4):327-30.Pyrenocine A, a phytotoxin produced by Pyrenochaeta terrestris (Hansen) Gorenz, Walker and Larson, possesses general antibiotic activity against plants, fungi, and bacteria. Effective doses for 50% inhibition (ED50s) are 4 micrograms/mL for onion seedling elongation; 14, 20, 20, and 25 micrograms/mL for the germination of asexual spores of Fusarium oxysporum f. sp. cepae, Fusarium solani f. sp. pisi, Mucor hiemalis, and Rhizopus stolonifer, respectively. Pyrenocine A also inhibits the linear mycelial growth of both P. terrestris and F. oxysporum with ED50s calculated as 77 and 54 micrograms/mL, respectively. Gram-positive bacteria are more susceptible to pyrenocine A than Gram-negative bacteria. ED50s are estimated as 30, 45, and 200 micrograms/mL for the inhibition of growth of Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, respectively, with Pseudomonas aeruginosa resistant to those concentrations tested. Pyrenocine A acts primarily as a biostatic rather than a biocidal agent with all organisms tested showing some degree of recovery when released from pyrenocine A. Pyrenocines B and C show little antibiotic activity in the bioassays performed.
1258The relationships between the toxicity and the primary and secondary structures of elicitinlike protein elicitors secreted by the phytopathogenic fungus Pythium vexans. Huet JC, Le Caer JP, Nespoulous C, Pernollet JC. Mol Plant Microbe Interact. 1995 Mar-Apr;8(2):302-10.Elicitins are toxic and signaling proteins secreted by Phytophthora spp. responsible for the incompatible reaction and systemic hypersensitive-like necroses of diverse plant species leading to resistance against fungal or bacterial plant pathogens. Such proteins were observed in the culture filtrate of another species of the Oomycete genus, Pythium vexans. Two alpha elicitinlike proteins were purified and sequenced. One of these novel elicitins (Vex2) exhibited a 100-residue sequence instead of 98 while the other (Vex1) had an N-glycosylation site, effectively glycosylated (equivalent of 16 hexose residues). In addition to the point mutations already observed in Phytophthora species, we found several novel amino acid changes. Furthermore, circular dichroism revealed some differences in their structure in solution compared with the Phytophthora elicitins that were correlated with specific point mutations. These sequences permitted the establishment of a phylogenic tree, suggesting that Pythium vexans is a species close to the Phytophthora genus. The toxicity of the Pythium vexans elictins to tobacco leaves was investigated and correlated with the occurrence of the carbohydrate moiety of one of the two isoforms, observed for the first time in an elicitin.
1271Three new cytochalasins produced by an endophytic fungus in the genus Rhinocladiella. Wagenaar MM, Corwin J, Strobel G, Clardy J. J Nat Prod. 2000 Dec;63(12):1692-5.Three new cytotoxic cytochalasins (1-3) and the previously reported cytochalasin E (4) were isolated from a culture of the endophytic fungus Rhinocladiella sp. using bioassay-guided fractionation. Extensive NMR and HRCIMS experiments identified these new compounds as 22-oxa-[12]-cytochalasins.
1280Inactivation of phytotoxin produced by the rice sheath blight pathogen Rhizoctonia solani.Sriram S, Raguchander T, Babu S, Nandakumar R, Shanmugam V, Vidhyasekaran P, Balasubramanian P, Samiyappan R. Can J Microbiol. 2000 Jun;46(6):520-4.The rice sheath blight pathogen, Rhizoctonia solani, produces a toxin designated as RS-toxin, a carbohydrate compound containing mainly alpha-glucose and mannose. Different microflora were tested for RS-toxin inactivation. Isolates of Trichoderma viride inactivated this toxin when it was provided as the sole food source, and these isolates reduced the severity of toxin-induced symptoms and electrolyte leakage from rice cells. The best-performing isolate, TvMNT7, produced two extracellular proteins of 110 and 17 kDa. The high molecular mass protein was shown to have alpha-glucosidase activity. The purified 110 kDa protein was able to reduce RS-toxin activity.
1281Neurotoxic mycotoxins: a review of fungal toxins that cause neurological disease in large animals. Plumlee KH, Galey FD. J Vet Intern Med. 1994 Jan-Feb;8(1):49-54.Five mycotoxins found in concentrates or roughages have been shown to cause neurologic disease in livestock. Fumonisin B1 is produced by Fusarium moniliforme and causes leukoencephalomalacia in horses. Swainsonine and slaframine are produced by Rhizoctonia leguminicola and cause mannose accumulation and parasympathomimetic effects, respectively. Lolitrems from Acremonium lolii and paspalitrems from Claviceps paspali are tremorgens found in grasses.
1292Toxicity of rhizonin A, isolated from Rhizopus microsporus, in laboratory animals. Wilson T, Rabie CJ, Fincham JE, Steyn PS, Schipper MA. Food Chem Toxicol. 1984 Apr;22(4):275-81.Maize culture material of 25 isolates of the genera Rhizopus and Mucor caused deaths in day-old unsexed Pekin ducklings when fed as a 50% (w/w) mixture with duckling feed. Nine of these isolates were tested for toxicity in young inbred male BD IX rats, which were fed a mixture of 50% (w/w) culture material and rat feed. Only one isolate of Rhizopus microsporus was clearly toxic, causing 100% mortality in rats within 10 days. Growth in rats was reduced by adding culture material of this isolate to the feed in concentrations of 2.5, 5, 10 or 20% (w/w). The same isolate of R. microsporus was used to produce the mycotoxin rhizonin A. Pure rhizonin A was dissolved in dimethylsulphoxide and given to young male partially inbred albino rats by gavage in single doses of 70, 96, 131 or 180 mg/kg. The lowest dose exceeded the LD100. Evaluated by light microscopy, lesions in livers and kidneys were similar in rats fed culture material and in those intubated with rhizonin A. Hepatocytes showed changes ranging from degeneration to necrosis, the liver-tissue architecture was changed by disassociation of liver cell cords and there was periportal bile-duct proliferation. Renal tubular epithelium showed changes ranging from degeneration to necrosis.
1374Preparation and antitumor activities of mitomycin C beta-(1-->6)-branched (1-->3)-beta-D-glucan conjugate. Usui S, Murashima K, Sakai M, Kiho T, Ukai S. Biol Pharm Bull. 1994 Sep;17(9):1165-70.The conjugate of mitomycin C (MMC) with carboxymethylated schizophyllan (CMSPG) which was prepared from monochloroacetic acid and schizophyllan (SPG), a beta-(1-->6)-branched (1-->3)-beta-D-glucan from Schizophyllum commune Fries, was synthesized by using 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide. The degree of the substitution of carboxymethyl groups in CMSPG was estimated as approximately 0.87, and locations of carboxymethyl groups in CMSPG were predominantly determined at O-4, O-6, and O-4, 6 positions in glucose residues. The contents of MMC in the conjugate were estimated to be between 8 and 12% (w/w). The conjugate showed successive monoexponential liberation, with a half-life of 7.2 h. Although the in vitro cytotoxicity of the conjugate against L1210 leukemia cells was similar to that of MMC when the cells were exposed for 24 and 48 h, the 50% growth-inhibitory concentration of the conjugate for L1210 was two times higher than that of MMC with exposure for 12 h. The antitumor activity of the conjugate against subcutaneously implanted sarcoma 180 solid tumor in mice by intraperitoneal (i.p.) administration was similar to that of MMC at a dose of 1.5 mg eq MMC per kg per d for both 7 times of continuous administration and 4 times of intermittent administration. However, the reduction in the number of leukocytes in the peripheral blood, which was the side effect of MMC, was suppressed by the intermittent administration of the conjugate. The conjugate maintained the ability to induce the tumor regressing factor and the neutrophil chemotactic factor in the serum.
1397Production, isolation, and antifungal activity of scytalidin, a metabolite of Scytalidium species. Stillwell MA, Wall RE, Strunz GM. Can J Microbiol. 1973 May;19(5):597-602. 
1398Scytalidin: a new fungitoxic metabolite produced by a Scytalidium species. Strunz GM, Kakushima M, Stillwell MA. J Chem Soc [Perkin 1]. 1972;18:2280-3. 
1405Neosordarin and hydroxysordarin, two new antifungal agents from Sordaria araneosa. Davoli P, Engel G, Werle A, Sterner O, Anke T. J Antibiot (Tokyo). 2002 Apr;55(4):377-82.Two novel antifungal agents belonging to the sordarin family have been isolated from fermentations of Sordaria araneosa by bioassay-guided purification and their structures elucidated by NMR techniques. Neosordarin (1) is closely related to the recently discovered hypoxysordarin (2), with only small differences on the aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose moiety. c (3) closely resembles sordarin (4), the only slight difference being the replacement of sordarose with altrose as the sugar unit.
1406Hypoxysordarin, a new sordarin derivative from Hypoxylon croceum. Daferner M, Mensch S, Anke T, Sterner O. Z Naturforsch [C]. 1999 Jul-Aug;54(7-8):474-80.Hypoxysordarin (1), a new sordarin derivative, was isolated from the fermentation broth of the facultative marine Hypoxylon croceum together with a new gamma-lactone, hypoxylactone (2) and sordarin (3). The structures were determined by spectroscopic methods. Sordarin (3) has previously been isolated from the terrestrial Sordaria araneosa (Sordariaceae). Like the parent compound hypoxysordarin exhibits high antifungal activities due to a specific inhibition of protein biosynthesis.
1407Sphaeropsis sapinea f. sp. cupressi. Evidente A, Sparapano L, Bruno G, Motta A. Phytochemistry. 2002 Apr;59(8):817-23.Two pimarane diterpenes structurally related to sphaeropsidins were isolated from the liquid culture of Sphaeropsis sapinea f. sp. cupressi, a plant pathogenic fungus causing a form of canker disease of Italian cypress (Cupressus sempervirens L.). The two metabolites, characterised by spectroscopic methods, were named sphaeropsidins D (0.40 mg l(-1)) and E (0.16 mg l(-1)). The same fungus produced sphaeropsidins A, B and C, sphaeropsidone and episphaeropsidone, which proved to be phytotoxic to cypress, and chlorosphaeropsidone and epichlorosphaeropsidone showing no phytotoxicity. Sphaeropsidin D assayed at 0.1 mg ml(-1) on severed cypress twigs caused leaf browning and necrosis on Cupressus macrocarpa, but no symptoms were observed on C. sempervirens and C. arizonica. Symptoms appeared in a period of time (6 days after toxin-treatment) shorter than that for sphaeropsidin A. Sphaeropsidin E assayed at 0.2 mg ml(-1) did not produce any symptom on the same cypress species tested with sphaeropsidin D.
1409Ampullosporines B,C,D,E1,E2,E3 and E4 from Sepedonium ampullosporum HKI-0053: structures and biological activities. Kronen M, Kleinwächter P, Schlegel B, Härtl A, Gräfe U. J Antibiot (Tokyo). 2001 Feb;54(2):175-8. 
1410Ampullosporin, a new peptaibol-type antibiotic from Sepedonium ampullosporum HKI-0053 with neuroleptic activity in mice. Ritzau M, Heinze S, Dornberger K, Berg A, Fleck W, Schlegel B, Härtl A, Gräfe U. J Antibiot (Tokyo). 1997 Sep;50(9):722-8.Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
1411Isolation and structure of peptaibolin, a new peptaibol from Sepedonium strains. Hülsmann H, Heinze S, Ritzau M, Schlegel B, Gräfe U. J Antibiot (Tokyo). 1998 Nov;51(11):1055-8. 
1418Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. I. Taxonomy, fermentation, isolation and biological activities. Hayashi M, Kim YP, Takamatsu S, Preeprame S, Komiya T, Masuma R, Tanaka H, Komiyama K, Omura S. J Antibiot (Tokyo). 1996 Jul;49(7):631-4.Selective growth inhibition against IL-6 dependent cells was detected in fermentation extracts of a fungal strain FO-4649 which was characterized as Sporothrix species. An active metabolite (1) termed chlovalicin was isolated together with ovalicin and two other ovalicin derivatives (compounds 3 and 4). Chlovalicin, a ovalicin derivative with a chlorinated methylene moiety at the C-1 position of the cyclohexane ring, dose-dependently inhibited the growth of IL-6 dependent MH60 cells (IC50, 7.5 microM) in the presence of 0.2 U/ml IL-6 and, to a lesser extent, the growth of B16 melanoma cells (IC50, 38 microM). Among the other three compounds, only ovalicin showed inhibitory activity (IC50, 27 microM) against MH60 cells. These four compounds did not show any antimicrobial activity at a concentration of 1000 micrograms/ml.
1443Atranones A-G, from the toxigenic mold Stachybotrys chartarum. Hinkley SF, Mazzola EP, Fettinger JC, Lam YF, Jarvis BB. Phytochemistry. 2000 Nov;55(6):663-73.Atranones A-G have been isolated from the toxigenic fungus Stachybotrys chartarum. These compounds contain several unusual features including an enol-lactone as part of a 3,7-dioxabicyclo[3.3.0]octane-2-one ring system fused to an 11-membered ring. Two new dolabellane diterpenes, related in structure to the atranones were also isolated, which suggests a diterpenoid origin for the C24 atranones.
1444Metabolite profiles of Stachybotrys isolates from water-damaged buildings and their induction of inflammatory mediators and cytotoxicity in macrophages. Nielsen KF, Huttunen K, Hyvarinen A, Andersen B, Jarvis BB, Hirvonen MR. Mycopathologia. 2002;154(4):201-5.The metabolite profiles of 20 Stachybotrys spp. isolates from Finnish water-damaged buildings were compared with their biological activities. Effects of purified compounds on cytotoxicity and production of inflammatory mediators such as nitric oxide, IL-6 and TNFalpha in murine RAW264.7 macrophage cells were studied. The 11 isolates belonging to the satratoxin-producing chemotype were highly cytotoxic to the macrophages. The isolates inducing inflammatory mediators all belonged to the atranone-producing chemotype, but pure atranones B, and D did not elicit a response in the bioassay. Altogether, cytotoxicity of Stachybotrys sp. isolates appear to be related to satratoxin production whereas the specific component inducing inflammatory responses in atranone-producing isolates remains obscure.
1445 FR901459, a novel immunosuppressant isolated from Stachybotrys chartarum No. 19392. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological activities. Sakamoto K, Tsujii E, Miyauchi M, Nakanishi T, Yamashita M, Shigematsu N, Tada T, Izumi S, Okuhara M. J Antibiot (Tokyo). 1993 Dec;46(12):1788-98.FR901459, a novel immunosuppressant, has been isolated from the fermentation broth of Stachybotrys chartarum No. 19392. The molecular formula of FR901459 was determined as C62H111N11O13. FR901459 was found to be a member of the cyclosporin family. However, it is structurally distinct from any other cyclosporins discovered so far, in that Leu is present at position 5 instead of Val. FR901459 was capable of prolonging the survival time of skin allografts in rats with one third the potency of cyclosporin A.
1446Identification of mycotoxins produced by species of Fusarium and Stachybotrys obtained from Eastern Europe. Szathmary CI, Mirocha CJ, Palyusik M, Pathre SV. Appl Environ Microbiol. 1976 Oct;32(4):579-84.Isolates of Fusarium and Stachybotrys spp. and crude extracts from these fungi were obtained from Hungary and the U.S.S.R. and used for the evaluation of the mycotoxins they produced. The cultures were grown on millet and oats and extracted in Budapest, Hungary (Veterinary Medical Research Institute) and chemically analyzed at the University of Minnesota using thin-layer chromatography (TLC), gas-liquid chromatography (GLC), gas chromatograph-mass spectrometry (GC-MS), and the rat skin bioassay. Zearalenone was found in most of the Fusarium cultures, T-2 toxin, neosolaniol, T-2 tetraol, and HT-2 toxin were found in extracts of Fusarium poae and F. sporotrichioies. A special effort was made to isolate the steroid-like toxins reported in the early Russian literature as sporofusarin and poaefusarin. None of the extracts from the Fusarium species yielded poaefusarin or sporofusarin when analyzed by our chemical methods or by those of L.E. Olifson, S.M. Kenina, and V.L. Kartashova, 1972. We therefore accounted for the toxicity of the Fusarium extracts as due to the 12,13,epoxytrichothecenes. One culture of Stachybotrys alternans yielded a macrocyclic ester of 12,13-epoxytrichothecene which, upon hydrolysis, yielded verrucarol; a steroid-like molecule (SB-3) was also isolated. The former had skin-irritant activity but SB-3 did not; the latter exhibited cardiac activity on the heart of the cockroach.
1447Stachybotrys toxins. 1. Jarvis BB, Salemme J, Morais A. Nat Toxins. 1995;3(1):10-6.Cultures of several isolates of Stachybotrys chartarum have produced a series of cytotoxic macrocyclic trichothecenes including two newly characterized congeners: isosatratoxin G and S-isosatratoxin H. Nine immunosuppressant phenylspirodrimanes (1-9) were isolated and characterized, the majority of which are newly reported compounds.
1448Microanatomical changes in alveolar type II cells in juvenile mice intratracheally exposed to Stachybotrys chartarum spores and toxin. Rand TG, Mahoney M, White K, Oulton M. Toxicol Sci. 2002 Feb;65(2):239-45.Stachybotrys chartarum is an important environmental fungus. We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores and to the trichothecene, isosatratoxin-F, both in vitro and in vivo, in a juvenile mouse model. This sensitivity is manifest as significant changes in the composition and normal metabolic processing of pulmonary surfactant. This study evaluated the effects of a single intratracheal exposure of S. chartarum spores and toxin on ultrastructure and dimensions of alveolar type II cells from juvenile mice. This was to determine whether there are concurrent morphological and dimensional changes in the alveolar type II cell that reflect the metabolic alterations in pulmonary surfactant that we observed in the treated mice. Marked ultrastructural changes were associated with alveolar type II cells in both S. chartarum and isosatratoxin-F treated animals compared to untreated, saline, and Cladosporium cladosporioides spore treated animals. These ultrastructural changes included condensed mitochondria with separated cristae, scattered chromatin and poorly defined nucleolus, cytoplasmic rarefaction, and distended lamellar bodies with irregularly arranged lamellae. Point count stereological analysis revealed a significant increase (p < 0.05) in lamellar body volume density in S. chartarum and isosatratoxin-treated animals after 48 h exposure. Mitochondria volume density was significantly lower in the isosatratoxin-F (48 h exposure) and S. chartarum treated (24 and 48 h exposure) animals compared to those in the other treatment groups. These results reveal that exposure to S. chartarum spores and toxin elicit cellular responses in vivo differently from those associated with exposure to spores of a nontoxigenic mold species. They also indicate that accumulation of newly secreted pulmonary surfactant in the alveolar space of S. chartarum and isosatratoxin-F treated animals might be a consequence of cellular trauma resulting in lamellar body volume density changes leading to increased release of pulmonary surfactant into the alveolar space.
1449Effects of satratoxins and other macrocyclic trichothecenes on IL-2 production and viability of EL-4 thymoma cells. Lee MG, Li S, Jarvis BB, Pestka JJ. J Toxicol Environ Health A. 1999 Aug 13;57(7):459-74.The macrocyclic trichothecenes are a group of potent protein synthesis inhibitors that have been encountered in indoor air and food as a result of infestation by the fungus Stachybotrys. To evaluate the capacity of these mycotoxins to alter immune functions, the effects of satratoxin G, H, F, roridin A, and verrucarin A on interleukin 2 (IL-2) production and viability were evaluated in a murine T-cell model. EL-4 thymoma cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin and concurrently exposed to various concentrations of the trichothecenes. Enzyme-linked immunosorbent assay (ELISA) of supernatants revealed that IL-2 concentrations at 24 and 72 h were significantly increased in cultures that were incubated in the presence of 0.5 to 1 ng/ml of satratoxin H, 1 to 5 ng/ml of isosatratoxin F, 0.1 to 0.5 ng/ml of roridin A, and 0.25 to 0.5 ng/ml of verrucarin A. However, IL-2 levels at these time points were significantly depressed when incubated in the presence of higher concentrations of satratoxin G (> or =2.5 ng/ml), satratoxin H and isosatratoxin F (> or =5 ng/ml), and roridin A and verrucarin A (> or =1 ng/ml). Cell viability, as measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, was depressed by each of the trichothecenes in a concentration-dependent manner. MTT responses were significantly decreased by as little as 0.5 ng/ml satratoxin G, roridin A, and verrucarin A and by 2.5 ng/ml of isosatratoxin F and satratoxin H. When these data were compared to those found in EL-4 cells for the 8-ketotrichothecene vomitoxin (deoxynivalenol), a common food contaminant, the macrocyclic trichothecenes were at least 100 times more potent. The results indicate that, at low concentrations, macrocyclic trichothecenes as a group could superinduce IL-2 production even while partially decreasing cell viability, whereas higher concentrations suppressed cytokine production and were markedly cytotoxic. The capacity of these compounds to disregulate cytokine production in a biphasic fashion may play an etiologic role in outbreaks of human illnesses associated with indoor Stachybotrys contamination.
1450Apoptosis induction by the satratoxins and other trichothecene mycotoxins: relationship to ERK, p38 MAPK, and SAPK/JNK activation. Yang GH, Jarvis BB, Chung YJ, Pestka JJ. Toxicol Appl Pharmacol. 2000 Apr 15;164(2):149-60.The satratoxins are members of the trichothecene mycotoxin family that are produced by the fungus Stachybotrys and that have been etiologically associated with building-related health problems. The purpose of this study was to relate cytotoxic and apoptotic capacities of satratoxins and other trichothecenes to the activation of three groups of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated protein kinase (ERK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK)). Two myeloid models, RAW 264.7 murine macrophage and U937 human leukemic cells were used. Upon evaluating representative trichothecenes in the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) cleavage assay, cytotoxicity was evident according to the following rank order: satratoxin G, roridin A, and verrucarin A > T-2 toxin, satratoxin F, H > nivalenol, and vomitoxin. Comparable results were found when measuring trichothecene-mediated apoptosis using DNA fragmentation and fluorescence microscopy assays, thus suggesting that cytotoxicity was mediated through an apoptotic process. Assessment of MAPK activation using Western blot analysis revealed that trichothecenes activated not only SAPK/JNK and p38 MAPK but also ERK. Activation of MAPKs by satratoxins and other trichothecenes correlated with and preceded apoptosis. The concentration of satratoxin G sufficient for protein synthesis inhibition correlated with that required for apoptosis and activation of all three MAPKs. Cycloheximide had similar effects to trichothecenes, suggesting that ribosome binding or protein synthesis inhibition may play roles in MAPK activation and apoptosis induction. Apoptosis induction by satratoxin G and vomitoxin was markedly enhanced when ERK activation was selectively inhibited by ERK-specific inhibitor PD98059, thus indicating a negative role for ERK. Inhibition of p38 MAPK activity with the p38-specific inhibitor SB203580 had no effect on apoptosis induction by the highly toxic satratoxin G. However, SB203580 moderately inhibited apoptosis induction by the less toxic trichothecene vomitoxin, thus implying a partial role of p38 MAPK in trichothecene-induced apoptosis. The results suggest that the satratoxins are among the most potent trichothecenes and that MAPKs may play integral roles in the diverse toxic manifestations of these mycotoxins.
1451Macrocyclic trichothecenes produced by Stachybotrys isolated from Egypt and eastern Europe. el-Maghraby OM, Bean GA, Jarvis BB, Aboul-Nasr MB. Mycopathologia. 1991 Feb;113(2):109-15.Twenty seven isolates of Stachybotrys chartarum, S. albipes, S. kampalensis and S. microspora from Egypt and Eastern Europe were tested for production of macrocyclic trichothecenes. Twenty of the 27 isolates, grown on rice seeds, were toxic to brine shrimp larvae. Based on TLC and HPLC analyses, 5 macrocyclic trichothecenes (verrucarin J, roridin E, satratoxins F, G & H) as well as trichoverrols were identified. When grown in liquid culture on rice extract medium, only 3 isolates were toxic and produced verrucarin J, roridin E and satratoxins G & H. Extracts from mycelial mats were more toxic than culture filterates of two isolates grown on rice extract and both contained the same macrocyclic trichothecenes (285.5 mg/4 L), in addition to trichoverrols A & B (31 mg/4 L) found in mycelial mats only. When grown on 3% sucrose Czapek's medium supplemented with peptone and yeast extract (still cultures), all isolates were non-toxic to brine shrimp and no trichothecenes could be detected in the extracts.
1452Trichothecenes produced by Stachybotrys atra from Eastern Europe. Jarvis BB, Lee YW, Cömezoglu SN, Yatawara CS. Appl Environ Microbiol. 1986 May;51(5):915-8.A total of 17 isolates of Stachybotrys atra isolated from various parts of Hungary and Czechoslovakia were grown on rice, and the toxin production of each isolate was analyzed by high-performance liquid chromatography. Of the 17 isolates, 14 produced macrocyclic trichothecenes (satratoxins F, G, and H, roridin E, and verrucarin J) as well as trichoverrols A and B. Most isolates produced satratoxins G and H in higher quantities than the other trichothecenes. The yield (in milligrams) of trichothecenes produced by one isolate grown on 800 g of rice was as follows: roridin E, 12; satratoxin F, 10; satratoxin G, 75; satratoxin H, 100; trichoverrol A, 15; and trichoverrol B, 30.
1453Stachylysin may be a cause of hemorrhaging in humans exposed to Stachybotrys chartarum. Vesper SJ, Vesper MJ. Infect Immun. 2002 Apr;70(4):2065-9.Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns such as nasal bleeding in adults and pulmonary hemosiderosis (PH) in infants. Seven of eight strains of S. chartarum isolated from homes of infants with PH in Cleveland, Ohio, and the strain from the lung of an infant with PH in Texas produced stachylysin in tryptic soy broth (TSB), whereas only one out of eight strains isolated from control homes produced stachylysin. However, all strains produced stachylysin when grown on TSB with 0.7% sheep's blood. When stachylysin was injected into Lumbricus terrestis, the erythrocruorin hemoglobin (absorbance peaks at 280 and 415 nm) was released, resulting in a lethal effect. These results support the hypothesis that stachylysin may be one agent responsible for hemorrhaging in humans.
1454Initial characterization of the hemolysin stachylysin from Stachybotrys chartarum. Vesper SJ, Magnuson ML, Dearborn DG, Yike I, Haugland RA. Infect Immun. 2001 Feb;69(2):912-6.Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns, including pulmonary hemorrhage and hemosiderosis. This fungus produces a hemolysin, stachylysin, which in its apparent monomeric form has a molecular mass of 11,920 Da as determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. However, it appears to form polydispersed aggregates, which confounds understanding of the actual hemolytically active form. Exhaustive dialysis or heat treatment at 60 degrees C for 30 min inactivated stachylysin. Stachylysin is composed of about 40% nonpolar amino acids and contains two cysteine residues. Purified stachylysin required more than 6 h to begin lysing sheep erythrocytes, but by 48 h, lysis was complete. Stachylysin also formed pores in sheep erythrocyte membranes.
1455Some cultural conditions that control production of verrucarin J, a cytotoxic metabolite of Stachybotrys chartarum. El-Kady IA, Moubasher MH. Zentralbl Mikrobiol. 1982;137(3):241-6.A suitable chemically defined culture medium was selected and some optimal conditions for the biosynthesis of the highly cytostatic and antifungal compound verrucarin J were reported. Medium of the following composition was favourable for the production of verrucarin J by Stachybotrys chartarum: sucrose, 50; NaNO3, 2.0; KH2PO4, 1.0; MgSO4, 0.5; KCl, 0.5; leucine, 1.0 and FeSO4, 0.01 (g/l of distilled water). Biosynthesis of verrucarin J was maximal (11.8 mg/l) at pH 6.5-7.0 and after incubation for 14 days at 25 degrees C.
1456Macrocyclic trichothecene toxins produced by a strain of Stachybotrys atra from Hungary. Harrach B, Mirocha CJ, Pathre SV, Palyusik M. Appl Environ Microbiol. 1981 Jun;41(6):1428-32.A strain of Stachybotrys atra isolated from a field case of stachybotryotoxicosis in Hungary was cultured in Hungary. All of the compounds toxic to brine shrimp were separated from the culture extract by solvent partition, column chromatography, and preparative thin-layer chromatography. Two of the toxic compounds were identified as verrucarin J and satratoxin H by comparison with pure standards resolved by high-pressure liquid chromatography and characterized by mass spectrometry. Two other toxic components were identified as roriden E and satratoxin G on the basis of their mass spectra. The fifth toxic compound was identified as a macrocyclic trichothecene based on the following findings: a positive 4-(p-nitrobenzyl)pyridine color reaction, hydrolysis resulting in verrucarol verified by combined gas chromatography-mass spectrometry, and a characteristic trichothecene proton-nuclear magnetic resonance spectrum. This macrocyclic trichothecene has a molecular ion (528) identical to satratoxin H, and its mass spectrum is similar; however, its Rf value on Silica Gel G differs.
1458Stachylysin may be a cause of hemorrhaging in humans exposed to Stachybotrys chartarum. Vesper SJ, Vesper MJ. Infect Immun. 2002 Apr;70(4):2065-9.Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns such as nasal bleeding in adults and pulmonary hemosiderosis (PH) in infants. Seven of eight strains of S. chartarum isolated from homes of infants with PH in Cleveland, Ohio, and the strain from the lung of an infant with PH in Texas produced stachylysin in tryptic soy broth (TSB), whereas only one out of eight strains isolated from control homes produced stachylysin. However, all strains produced stachylysin when grown on TSB with 0.7% sheep's blood. When stachylysin was injected into Lumbricus terrestis, the erythrocruorin hemoglobin (absorbance peaks at 280 and 415 nm) was released, resulting in a lethal effect. These results support the hypothesis that stachylysin may be one agent responsible for hemorrhaging in humans.
1465Production of a toxin stemphol by Stemphylium species. Solfrizzo M, Strange RN, Sabia C, Visconti A. Nat Toxins. 1994;2(1):14-8.Five of 11 isolates of Stemphylium botryosum Wallr. from oilseed rape produced the phytotoxin stemphol when cultured on rice, with yields varying from 15.0 to 98.4 mg/kg, and three of them also produced the toxin on Czapek Dox (CD) liquid medium supplemented with cations (0.12-0.31 mg/L) and potato-dextrose (PD) broth (0.37-1.47 mg/L). In liquid cultures about 95% of stemphol was found in the mycelium, and toxin production was slightly increased when cultures were exposed to near UV light rather than being grown in the dark. The LD50 concentrations for stemphol against isolated cells of oilseed rape and chickpea were 8.4 and 7.0 microM, respectively. One isolate of S. majusculum (strain no. 135459) produced much greater amounts of stemphol, i.e., 22.8 mg/L, 535.3 mg/L, and 548 mg/kg when grown on CD, PD, and rice, respectively. Leaves of oilseed rape, artificially infected with S. majusculum and bearing lesions that occupied an average of 70% of the lamina contained 0.9 microgram stemphol per gram dry weight of leaf tissue.
1470 Isolation and characterization of a cytotoxic metabolite of Talaromyces bacillosporus. Ishii K, Itoh T, Kobayashi K, Horie Y, Ueno Y. Appl Environ Microbiol. 1995 Mar;61(3):941-3.A cytotoxic metabolite, talarotoxin, was isolated from a fungus, Talaromyces bacillosporus IFO 8397, cultured on rice. The structure of the toxin was elucidated and found to contain a pyrrolizidinedione connected with a trans delta 1-octalin through a conjugated triene.
1471The search for a taxol-producing microorganism among the endophytic fungi of the Pacific yew, Taxus brevifolia. Stierle A, Strobel G, Stierle D, Grothaus P, Bignami G. J Nat Prod. 1995 Sep;58(9):1315-24.Endophytic microbes associated with the Pacific yew tree, Taxus brevifolia, were examined as potential sources of the anticancer drug taxol [1], a secondary metabolite of the host organism. The first promising organism found was the novel fungus, Taxomyces andreanae, which was isolated from the inner bark of a yew tree growing in northwestern Montana. It appears to produce taxol and other taxanes in de novo fashion when grown in semi-synthetic liquid media. The presence of 1 in the fungal extract was confirmed by mass spectrometry, comparative chromatographic behavior with "yew" taxol, reactivity with taxol-specific monoclonal antibodies, and 9KB cytotoxicity studies. Both acetate-1-14C and phenylalanine UL-14C served as precursors of taxol-14C in fungal culture labeling studies, confirming the de novo synthesis of 1 by the fungus. Immunoassay techniques are currently being used to screen extracts of Taxomyces andreanae for new taxanes, and to determine if other endophytic fungi are taxol producers.
1472Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Stierle A, Strobel G, Stierle D. Science. 1993 Apr 9;260(5105):214-6.Taxomyces andreanae, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew, Taxus brevifolia. The fungus is hyphomyceteous and, when grown in a semi-synthetic liquid medium, produced taxol and related compounds. Taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol. Both [1-14C]acetic acid and L-[U-14C]phenylalanine served as precursors of [14C]taxol in fungal cultures. No taxol was detected in zero-time cultures or in the small agar plugs used to inoculate the culture flasks.
1477Thielavin A and B, new inhibitors of prostaglandin biosynthesis produced by Thielavia terricola. Kitahara N, Endo A, Furuya K, Takahashi S. J Antibiot (Tokyo). 1981 Dec;34(12):1562-8.Two potent inhibitors of prostaglandin biosynthesis, thielavin A (C31H34O10) and B (C29H30O10), were isolated from cultures of Thielavia terricola. Both of these compounds were shown to be structurally related to depsides, thus consisting of three hydroxybenzoic acid groups. Concentrations required for 50% inhibition of the conversion of 14C-arachidonic acid into prostaglandins F2 alpha plus E2 by microsomes of ram seminal vesicles were 12 microM for thielavin A and 9 microM for thielavin B, respectively. Of the enzymatic steps involved in prostaglandin synthesis, thielavin A specifically inhibited the conversion of arachidonic acid into prostaglandin H2, while prostaglandin E2 synthesis from the endoperoxide was the most sensitive to thielavin B. Thromboxane A2 synthesis from prostaglandin H2 in bovine platelet microsomes were inhibited by 50% at concentrations of 150 and 350 microM of thielavin A and B, respectively. Thielavin B was significantly effective on carrageenan-induced oedema of rats when administered intravenously but on on oral administration. The anti-inflammatory activity was not detectable with thielavin A either on intravenous injection or on oral administration.
1478Isolation and biological activity of thielocins: novel phospholipase A2 inhibitors produced by Thielavia terricola RF-143. Matsumoto K, Tanaka K, Matsutani S, Sakazaki R, Hinoo H, Uotani N, Tanimoto T, Kawamura Y, Nakamoto S, Yoshida T. J Antibiot (Tokyo). 1995 Feb;48(2):106-12.Thielocins A2 alpha, A2 beta, A3, B1, B2 and B3 were isolated as a novel family of phospholipase A2 inhibitors from the fermentation broth of Thielavia terricola RF-143 together with thielavins and thielocins A1 alpha and A1 beta. The most potent inhibitory activity (IC50 = 0.0033 microM) against rat group II phospholipase A2 was shown by thielocin A1 beta. Against human group II phospholipase A2, thielocin B3 (IC50 = 0.076 microM) was the most potent.
1479Specificity of sensitivity to mycocin from Tilletiopsis flava BKM Y-2838] Golubev VI, Churkina LG. Mikrobiologiia. 2001 Jan-Feb;70(1):51-4.The mycocinogenous strain Tilletiopsis flava VKM Y-2823 was found to possess fungicidal activity at pH 3.5-4.5, which was retained after curing the strain by eliminating the extrachromosomal genetic elements. The mycocin produced by the strain had a molecular mass of more than 10 kDa and was readily inactivated by heating and treatment with protease K. This mycocin was found to be active against species of the anamorphic genus Tilletiopsis. The overwhelming majority of other representatives of the order Tilletiales, as well as ascomycetous and basidiomycetous yeasts, which either form or did not from ballistospores of the orders Sporidiales and Tremellales, were resistant to it.
1483The production of alamethicins by Trichoderma spp. Brewer D, Mason FG, Taylor A. Can J Microbiol. 1987 Jul;33(7):619-25. National Research Council of Canada, Atlantic Research Laboratory, Halifax, N.S.The production of polypeptides containing a high percentage of 2-methylalanine residues by a number of isolates of Trichoderma spp. has been examined. It has been shown that good yields (0.5-1.0 g L-1) can be achieved on synthetic media provided an insoluble carbohydrate is included and provided single-spore isolates that have this production ability are selected from time to time. Such yields could not be obtained on any single nitrogen source investigated, but a mixture of potassium nitrate, glutamine, and 2-methylalanine was effective. It was shown that at least eight polypeptides were produced in shake-flask or tank fermentation and that the proportions of these metabolites depended on the fermentation temperature, its pH, age, and aeration. Fermentation conditions for enhancing the production (independently) of two of the metabolites at the expense of the others are given. These two metabolites have been obtained in crystalline form and details of some of their physical and chemical properties are given.
1484Trichoderma atroviride G-protein alpha-subunit gene tga1 is involved in mycoparasitic coiling and conidiation. Rocha-Ramirez V, Omero C, Chet I, Horwitz BA, Herrera-Estrella A. Eukaryot Cell. 2002 Aug;1(4):594-605.The soil fungus Trichoderma atroviride, a mycoparasite, responds to a number of external stimuli. In the presence of a fungal host, T. atroviride produces hydrolytic enzymes and coils around the host hyphae. In response to light or nutrient depletion, asexual sporulation is induced. In a biomimetic assay, different lectins induce coiling around nylon fibers; coiling in the absence of lectins can be induced by applying cyclic AMP (cAMP) or the heterotrimeric G-protein activator mastoparan. We isolated a T. atroviride G-protein alpha-subunit (Galpha) gene (tgal) belonging to the fungal subfamily with the highest similarity to the Galpha1 class. Generated transgenic lines that overexpress Galpha show very delayed sporulation and coil at a higher frequency. Furthermore, transgenic lines that express an activated mutant protein with no GTPase activity do not sporulate and coil at a higher frequency. Lines that express an antisense version of the gene are hypersporulating and coil at a much lower frequency in the biomimetic assay. The loss of Tgal in these mutants correlates with the loss of GTPase activity stimulated by the peptide toxin Mas-7. The application of Mas-7 to growing mycelial colonies raises intracellular cAMP levels, suggesting that Tgal can activate adenylyl cyclase. In contrast, cAMP levels and cAMP-dependent protein kinase activity drop when diffusible host signals are encountered and the mycoparasitism-related genes ech42 and prb1 are highly expressed. Mycoparasitic signaling is unlikely to be a linear pathway from host signals to increased cAMP levels. Our results demonstrate that the product of the tga1 gene is involved in both coiling and conidiation.
1485Antibiotic activity of an isocyanide metabolite of Trichoderma hamatum against rumen bacteria.Liss SN, Brewer D, Taylor A, Jones GA. Can J Microbiol. 1985 Sep;31(9):767-72.A metabolite of Trichoderma hamatum, 3-(3-isocyanocyclopent-2-enylidene)propionic acid, was tested for its effects on growth of and carbohydrate metabolism in 11 strains of functionally important rumen bacteria. To standardize the biological activity of this unstable metabolite, a rapid, aerobic disc diffusion assay was developed using Escherichia coli ATCC 11775. In an anaerobic broth dilution assay using a medium lacking rumen fluid and containing a soluble carbohydrate, the minimum inhibitory concentration of the metabolite which completely inhibited growth of the rumen bacteria for 18 h at 39 degrees C was generally less than 10 micrograms X mL-1; however, the minimum inhibitory concentrations for Megasphaera elsdenii B159 and Streptococcus bovis Pe(1)8 were 10-25 and 25-64 micrograms X mL-1, respectively. In general, the Gram-negative strains were more sensitive than the Gram positive. The minimum inhibitory concentration for Bacteroides ruminicola 23 grown with glucose was 1 micrograms X mL-1; for B. ruminicola GA33 (glucose), B. succinogenes S85 (cellobiose), and Succinivibrio dextrinosolvens 24 (maltose), it was 2 microgram X mL-1. When added to a cellulose-containing rumen fluid medium, 1-4 micrograms X mL-1 of the metabolite delayed cellulose hydrolysis by B. succinogenes S85, Ruminococcus albus 7, and R. flavefaciens FD1 for up to 4 days, and 6-7 micrograms X mL-1 prevented hydrolysis for at least 1 month. In the presence of the metabolite, the proportion of acetate produced from soluble carbohydrate by the majority of strains increased, but with some strains net production of acetate decreased relative to production of other acidic fermentation products.(ABSTRACT TRUNCATED AT 250 WORDS)
1486MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma harzianum. II. Physico-chemical properties and structural elucidation. Lee CH, Koshino H, Chung MC, Lee HJ, Hong JK, Yoo JS, Kho YH. J Antibiot (Tokyo). 1997 Jun;50(6):474-8.New melanin synthesis inhibitors (MR566A and B) and six related known isocyanocyclopentenes were isolated from the fermentation broth of Trichoderma harzianum, and their structures were elucidated by spectroscopic methods. The structures of novel isocyanides, MR566A (1) and B (2), were elucidated as 1-(3-chloro-1,2-dihydroxy-4-isocyano-4-cyclopenten-1-yl)etha nol, 1-(1,2,3-trihydroxy-3-isocyano-4-cyclopenten-1-yl)ethanol, respectively. The structure of novel oxazole, MR93B (9), was elucidated as 4-[(1Z)-3-hydroxy-2-hydroxymethyl-1-propen-1-yl]oxazole.
1487Ovine ill-thrift in Nova Scotia. 9. Production of experimental quantities of isocyanide metabolites of Trichoderma hamatum. Brewer D, Feicht A, Taylor A, Keeping JW, Taha AA, Thaller V. Can J Microbiol. 1982 Nov;28(11):1252-60.Laboratory cultures of Trichoderma hamatum produce metabolites that are characterized by an isocyanide functionality. Three such metabolites predominate. One is the known compound trichoviridin (I). The other two, described here for the first time, are 3-(3-isocyano-6-oxabicyclo[3,1,0]hex-2-en-5-yl)acrylic acid (II) and a very unstable compound 3-(3-isocyanocyclopent-2-enylidene-)propionic acid (III). Production of these three metabolites by a random sample of wild isolates of the fungus has been examined. At least one of these isocyanides was isolated from all cultures in which the culture broth inhibited the growth of Micrococcus luteus. The relative amounts of the three isocyanides produced by individual isolates were not the same and cultures were found in which I, II, or III was the main product. The isocyanide III was produced by all wild isolates which had antibiotic activity in their culture broth, and it was present in the concentration range 2-40 mg X L-1
1488Koninginin C: a biologically active natural product from Trichoderma koningii. Parker SR, Cutler HG, Schreiner PR. Biosci Biotechnol Biochem. 1995 Jun;59(6):1126-7.Koninginin C, a congener of koninginins A and B, was isolated from Trichoderma koningii fermented on a shredded wheat medium. The compound inhibited the growth of etiolated wheat coleoptiles by 100% at 10(-3) M. It was a fine, white crystalline substance with a molecular formula of C16H28O4 and a melting point of 70-72 degrees C.
1489 Koninginin G, a new metabolite from trichoderma aureoviride Cutler HG, Cutler SJ, Ross SA, Sayed KE, Dugan FM, Bartlett MG, Hill AA, Hill RA, Parker SR. J Nat Prod. 1999 Jan;62(1):137-9.A new metabolite, koninginin G (1), was isolated from a strain of Trichoderma aureoviride and its structure established by the interpretation of spectroscopic data. The metabolite significantly inhibited the growth of etiolated wheat coleoptiles by 56% at 10(-3) M.
1490Paracelsin; characterization by NMR spectroscopy and circular dichroism, and hemolytic properties of a peptaibol antibiotic from the cellulolytically active mold Trichoderma reesei. Part B. Brückner H, Graf H, Bokel M. Experientia. 1984 Nov 15;40(11):1189-97.Paracelsin, a hemolytic and membrane active polypeptide antibiotic of the peptaibol class which is excreted by the mold Trichoderma reesei, was obtained by a simplified and rapid isolation procedure utilizing hydrophobic adsorber resins. Investigation by 13C nuclear magnetic resonance spectroscopy and circular dichroism revealed considerable helical portions in solution, and the very recently accomplished sequence determination of paracelsin allows the discussion of the results with regard to the closely related analogues, alamethicin and suzukacillin. A selective cleavage of the peptide was achieved by careful treatment with various acids, and a buffer of pH 8.25 and of high ionic strength made possible the quantitative determination of the C-terminal phenylalaninol released by means of ion-exchange chromatography. The significance of the production of paracelsin and related mycotoxins of the peptaibol class, exhibiting various kinds of biological activity, is discussed with respect to the extensive effort being made towards biotechnological applications of species, strains and cellulolytically highly active mutants of the fungus Trichoderma.
1491Structural and membrane modifying porperties of suzukacillin, a peptide antibiotic related to alamethicin. Part B. Pore formation in black lipid films. Boheim G, Janko K, Leibfritz D, Ooka T, König WA, Jung G. Biochim Biophys Acta. 1976 Apr 16;433(1):182-99.Suzukacillin, a polypeptide consisting of presumably 23 amino acids and 1 phenylalaninol, is produced by a Trichoderma viride strain No. 1037 and it can be isolated from the culture medium. It shows membrane-modifying properties similar to those of alamethicin. Discrete condustance fluctuations indicate the formation of oligomer pores of varying diameter. On the basis of voltage jump relaxation experiments evidence is given that the dimer is the nucleation state from which pore formation starts and the oligomer disappears. According to the voltage-current characteristics, voltage-dependent and voltage-independent conductances are observed. A slow process is involved, which can be interpreted as a change in the equilibrium distribution between different conformations of the suzukacillin monomer at the membrane interphase. This change results from its interaction with the lipid matrix. Differences in experimental observations between suzukacillin and alamethicin are attributed to the relatively larger alpha-helix and higher number of aliphatic side chains of the suzukacillin monomer and to a more intense interaction with the lipid membrane. This leads to a higher probability of forming dimers from monomers and to the occurrence of "inactivation".
1492Isolation, sequence, and conformation of seven trichorzianines B from Trichoderma harzianum. Rebuffat S, el Hajji M, Hennig P, Davoust D, Bodo B. Int J Pept Protein Res. 1989 Sep;34(3):200-10.From the antagonistic fungus Trichoderma harzianum, a group of acidic new peptides, trichorzianines B (TB), was isolated in addition to neutral trichorzianines A (TA) previously studied. TA and TB exhibit various biological activities related to their membrane properties and a different behaviour of the two groups was noticed. As observed for other peptaibols, TB consist in a microheterogeneous mixture which was resolved into pure peptides by reversed-phase C18 HPLC. The sequence of the seven main isolated TB, namely TB IIa, TB IIIc, TB IVb, TB Vb, TB VIa, TB VIb, TB VII, was determined by the combined use of positive ion FAB mass spectrometry and 2D 1H n.m.r. spectroscopy, including COSY and NOESY experiments. TB differ from the corresponding TA only by the replacement of Gln 18 in the TA sequence by a glutamic acid. The 1H n.m.r. data suggested that the TB are mainly organized in an alpha helix.
1493Isolation and sequence determination of trichorzianines A antifungal peptides from Trichoderma harzianum. el Hajji M, Rebuffat S, Lecommandeur D, Bodo B. Int J Pept Protein Res. 1987 Feb;29(2):207-15.Trichorzianines A, membrane active peptides of the peptaibol class, were isolated from cultures of the mould Trichoderma harzianum. Trichorzianines A were separated into pure components by HPLC on octadecyl bonded and SiO2 phases successively. Nine trichorzianines A (IIa, IIIa, IIIb, IIIc, IVb, Vb, VIa, VIb and VII) were isolated from the complex microheterogeneous mixture. Their N-terminal amino acid is acetylated, the C-terminal amino alcohol is either tryptophanol or phenylalaninol, 7 to 8 of the 19 residues are alpha-aminoisobutyric acid. Gas chromatography on a chiral phase showed isovaline to have the D-configuration and all the other optically active amino acids and amino alcohols to have the L-configuration. The amino acid sequences were determined from their positive ion FAB mass spectra which exhibited the preferential cleavage of the Aib 12-Pro 13 amide bond as a main fragmentation. The resulting fragments subsequently underwent amide bond ruptures that generated two series of abundant acylium ions which enabled direct determination of the 1-19 sequence. The relative position of the isomeric amino acids in the sequence of trichorzianine AVII was assigned from analysis of the N- and C-terminal oligopeptides yielded by its selective acidic hydrolysis. The microheterogeneity of trichorzianines A results mainly from single or multiple substitution of amino acids at the specific positions 5, 14, 16 and 19.
1494Methods for the detection of trichothecenes. Eppley RM. J Assoc Off Anal Chem. 1975 Sep;58(5):906-8.The trichothecenes are a group of fungal metabolites with a tetracyclic, sesquiterpenoid ring system and include a number of compounds which are highly toxic. These compounds are produced by various species of the imperfect fungi including members of the following genera: Calonectria, Fusarium, Myrothecium, Stachybotrys, Trichoderma, and Trichothecium. Both biological and chemical methods for detection of various trichothecenes are reviewed. Some of the bioassay techniques in use for the detection of the various trichothecenes include the rabbit dermal toxicity tests, cytotoxicity, and inhibition of protein synthesis tests; these are highly sensitive but lace specificity. The sensitivity of these tests for the T-2 toxin are 0.005 mug for rabbit skin toxicity, 0.03 mug/ml for inhibition of protein synthesis in rabbit reticulocytes, and less than 1 mug/ml for cytotoxicity to human karyoblast cells. In the present state of development of the chemical assay methods, thin layer and gas-liquid chromatography are specific for various trichothecenes but lack sensitivity. The lower detection limit of the trichothecenes on thin layer plates varies from 0.2 to 2-3 mug/spot while gas-liquid chrommatography has a reported sensitivity of approximately 0.05 mug/injection.
1495Isolation and structure of harzianum A: a new trichothecene from Trichoderma harzianum. Corley DG, Miller-Wideman M, Durley RC. J Nat Prod. 1994 Mar;57(3):422-5.A new trichothecene, harzianum A [1], was isolated from the soil-borne fungus Trichoderma harzianum. The structure of 1 was determined by extensive spectral analyses including the nmr techniques of PS-COSY, HMQC, HMBC, and NOESY. Harzianum A [1] contains a (Z,E,E)-2,4,6-octatriendioic acid esterified on the 4 beta hydroxyl group of trichodermol and is structurally related to the trichoverroids. Harzianum A [1] showed no cytotoxicity against baby hamster kidney cells, no activity against Gram-negative and Gram-positive bacteria, but modest antifungal activity at 100 micrograms/ml
1496Membrane-modifying properties of the pore-forming peptaibols saturnisporin SA IV and harzianin HA V. Rebuffat S, Duclohier H, Auvin-Guette C, Molle G, Spach G, Bodo B. FEMS Microbiol Immunol. 1992 Sep;5(1-3):151-60.Harzianin HA V and saturnisporin SA IV are alpha-amino isobutyric-containing peptides with 18- and 20-residue chain length, respectively. They were isolated from in vitro cultures of Trichoderma species and their sequences were determined by the combined use of positive ion FAB mass spectrometry and NMR. In organic solvent solution, both peptides exhibited the same predominant alpha-helical secondary structure including a hinge at the level of the central Pro residue, as deduced from NMR data. Their interaction with neutral phospholipid bilayers was shown to induce leakage of the material entrapped in small unilamellar vesicles composed of egg phosphatidylcholine/cholesterol (7/3). When incorporated into neutral planar lipid bilayers, they promoted voltage-gated channels. The concentration- and voltage-dependences of the ionic conductances induced by these peptides were studied in macroscopic current-voltage experiments. Single-channel measurements showed that whilst SA IV developed non-integral multi-open states similar to those induced by alamethicins, but with faster kinetics, the shorter analogue, HA V promoted much smaller-sized conducting aggregates in agreement with macroscopic conductance data.
1497 New mycotoxin, trichotoxin A, from Trichoderma viride isolated from southern leaf blight-infected corn. Hou CT, Ciegler A, Hesseltine CW. Appl Microbiol. 1972 Jan;23(1):183-5. 
1498of new sequences of peptaibol antibiotics trichotoxins A-40 by on-line liquid chromatography-electrospray ionization mass spectrometry. Jaworski A, Brückner H. J Chromatogr A. 1999 Nov 12;862(2):179-89.Using high-performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) the sequences of the microheterogeneous peptide mixture of the 18-residue "peptaibol" antibiotics trichotoxins A-40, isolated from the mold Trichoderma viride strain NRRL 5242, were reinvestigated. The structures of two major and one minor component [J. Chromatogr., 296 (1984) 236] could be confirmed and hitherto not known sequences of a further major and two minor peptides could be determined. It is demonstrated that ESI-MS in the positive ionization mode is advantageously completed by applying negative ionization. The methods used make possible the sequence determination of components of peptaibols without previous isolation and allow, in certain cases, sequencing of peptides which are incompletely or not resolved by HPLC.
1499Isolation and characterization of viridin, a new 65 kDa antifungal protein from the mould Trichoderma viride. Hao JJ, Geng C, Xie W, Gong Z, Liu WY, Wang E. Biol Chem. 1999 Oct;380(10):1243-5.A new extracellular antifungal protein with a yield of 10 mg per liter was isolated from the culture medium of the mould Trichoderma viride. The protein, which we named viridin, was purified by carboxymethyl-cellulose cation-exchange chromatography and Superose 12 HR 10/30 high-performance liquid chromatography. Viridin, a basic protein of approximately 65 kDa as determined by SDS-PAGE, inhibits the growth of the cotton pathogen Verticillum dahliae, the IC50 being 6 microM.
1500Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum. Vicente MF, Cabello A, Platas G, Basilio A, Diez MT, Dreikorn S, Giacobbe RA, Onishi JC, Meinz M, Kurtz MB, Rosenbach M, Thompson J, Abruzzo G, Flattery A, Kong L, Tsipouras A, Wilson KE, Pelaez F. J Appl Microbiol. 2001 Nov;91(5):806-13.AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.
1516Roseocardin, a novel cardiotonic cyclodepsipeptide from Trichothecium roseum TT103. Tsunoo A, Kamijo M, Taketomo N, Sato Y, Ajisaka K. J Antibiot (Tokyo). 1997 Dec;50(12):1007-13.A new cyclodepsipeptide, designated roseocardin, was isolated from the culture broth of Trichothecium roseum TT103. Roseotoxin B and destruxins A and B were also isolated during the same procedure. The structure of roseocardin was determined by EI-MS, NMR and X-ray crystallographic analysis. Roseocardin as well as the other cyclodepsipeptides were shown to produce positive inotropic effects on rat heart muscles.
1517Significance of toxic metabolites of the fungus Trichothecium roseum Link ex Fr. for viticulture] Schwenk S, Altmayer B, Eichhorn KW. Z Lebensm Unters Forsch. 1989 Jun;188(6):527-30.The plant-pathogen fungus Trichothecium roseum produces in vitro as well as in vivo the toxic metabolites trichothecin, trichothecolone and rosenonolactone. Trichothecin is cytotoxic and inhibits the alcoholic fermentation. It is not metabolized by yeast during the alcoholic fermentation. All toxins showed a minor biological activity against microorganisms other than yeast. Trichothecin caused a bitter taste in wine at higher toxin concentrations (greater than 5 mg/l). Trichothecin was detected in a few samples of wine of higher quality.
1518Selective effect of trichotecolone on hemopoietic tumor cells. Goetsch L, Thomasset N, Vila J, Philip I, Doré JF. Anticancer Res. 1990 Jul-Aug;10(4):1013-7.The effects of trichothecolone, a mycotoxin produced by the mould Trichothecium roseum, were tested at graded concentrations (50 to 250 micrograms/ml) on the in vitro growth of human and murine normal (CFU-GM, IARC 171, FDC-P2) and tumoral (HL60, P388, L1210) hemopoietic cells. A selective cytotoxicity towards tumor cells was observed: an irreversible, concentration dependent inhibition of growth being seen on all tumor cell lines under consideration, while normal cells appeared to be rather insensitive to this drug. In vivo, trichothecolone significantly increased the survival of mice bearing P388 leukemia: a 150 mg/kg/dose, 5 times a day, for 5 days led to a T/C of 145%. Both in vitro and in vivo data suggest that trichothecolone may be an interesting antitumor agent, particularly considering the clear difference in sensitivity of normal and tumor cells to this drug.
1519Synthesis of sesquiterpene metabolites in a Trichothecium roseum culture] Maksimova RA, Khuratova BG, Petrykina EI, Leĭkina MI. Nauchnye Doki Vyss Shkoly Biol Nauki. 1985;(6):96-9.During the cultivation Trichothecium roseum forms biologically active sesquiterpenes in particular trichothecin and trichothecolon. The quantitative ratio of these compounds in cultural liquid changes depending on the cultivation conditions. The compounds taking part in terpenoids shant specifically increase the synthesis of sesquiterpenes in fungus culture. A possibility of intertransformation of different trichothecenes provides the stability of the fungus-producent to its toxical metabolites. A fermental system carrying out the transformation of trichothecin into trichotecolon has been revealed.
1520Trichodion, a new inhibitor of inflammatory signal transduction pathways from a Trichosporiella species. Erkel G. FEBS Lett. 2000 Jul 21;477(3):219-23.In a search for new inhibitors of the IFN-gamma mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, the novel pyran-dione trichodion was isolated from fermentations of the imperfect fungus Trichosporiella sp. 20-95. The compound inhibits the IFN-gamma mediated expression of the reporter gene with IC(50) values of 21-42 microM (5-10 microgram/ml). The NF-kappaB and AP-1 mediated expression of the reporter gene are inhibited with IC(50) values of 42-84 microM (10-20 microgram/ml) and 21 microM (5 microgram/ml) respectively. Western blotting with COX-2 and NOS II antibodies showed that the expression of both proinflammatory enzymes is almost completely inhibited at 21-42 microM (5-10 microgram/ml) in LPS/IFN-gamma stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the NF-kappaB dependent pathway is due to the stabilization of the IkappaB protein and the inhibition of the IFN-gamma dependent signaling is caused by an inhibition of the phosphorylation of the STAT1alpha transcription factor.
1521Trichodion, a new bioactive pyrone from a Trichosporiella species. Erkel G, Rether J, Anke T, Sterner O. J Antibiot (Tokyo). 2000 Dec;53(12):1401-4. 
1524(-)-Terpestacin and L-tenuazonic acid, inducers of pigment and aerial mycelium formation by Fusarium culmorum JP 15. Schlegel B, Schmidtke M, Dörfelt H, Kleinwächter P, Gräfe U. J Basic Microbiol. 2001;41(3-4):179-83.Surface cultures of Fusarium culmorum JP15 were found to respond to extracts of other fungi by enhanced production of orange-red fusarubin pigments and formation of aerial mycelium. Two inducers from strain Ulocladium sp. HKI 0226, the new (-)-terpestacin (1) and L-tenuazonic acid (2), were isolated. 1 inhibited syncytium formation by cells infected with respiratory syncytial virus (RSV).
1531Comparison of balanol from Verticillium balanoides and ophiocordin from Cordyceps ophioglossoides. Boros C, Hamilton SM, Katz B, Kulanthaivel P. J Antibiot (Tokyo). 1994 Sep;47(9):1010-6.Recently, we reported the isolation of the potent protein kinase C inhibitor balanol (1) from the fungus Verticillium balanoides. In an earlier study, König et al. reported the isolation of ophiocordin (3), a structural isomer of 1, from the fungus Cordyceps ophioglossoides. The present study was designed to clarify whether or not balanol and ophiocordin are different compounds. The results indicated that the two fungi produced the same compound, the structure being that assigned to balanol. In addition, a thirty-fold increase in the production of balanol from V. balanoides was observed when the culture medium was changed from cornmeal/tomato paste to soy meal/glycerol.
1532 Cephalochromin, dihydroisoustilaginoidin A, and iso-ustilaginoidin A from Verticillium sp. K-113.Matsumoto M, Minato H, Kondo E, Mitsugi T, Katagiri K. J Antibiot (Tokyo). 1975 Aug;28(8):602-4. 
1533 Isolation of 11 , 11' -dihydroxychaetocin from Verticillium tenereum] Hauser D, Loosli HR, Niklaus P. Helv Chim Acta. 1972;55(6):2182-7. 
1534 Verticillin A, a new antibiotic from Verticillium sp. Katagiri K, Sato K, Hayakawa S, Matsushima T, Minato H. J Antibiot (Tokyo). 1970 Aug;23(8):420-2. 
1535 Studies on the metabolites of Verticillium sp. structures of Verticillins A, B, and C. Minato H, Matsumoto M, Katayama T. J Chem Soc [Perkin 1]. 1973;17:1819-25. 
1541UCA1064-B, a new antitumor antibiotic isolated from Wallemia sebi: production, isolation and structural determination.Takahashi I, Maruta R, Ando K, Yoshida M, Iwasaki T, Kanazawa J, Okabe M, Tamaoki T. J Antibiot (Tokyo). 1993 Aug;46(8):1312-4. 
1542Studies on a toxic metabolite from the mould Wallemia. Wood GM, Mann PJ, Lewis DF, Reid WJ, Moss MO. Food Addit Contam. 1990 Jan-Feb;7(1):69-77.While monitoring the occurrence of toxigenic moulds in foods, using a bioassay screen, it was shown that an isolate of Wallemia sebi produced toxic effects in several of the bioassays. The toxic metabolite was isolated and purified using solvent extraction, TLC and HPLC coupled with the brine shrimp assay to monitor the toxic fractions. The purified toxin, which we propose to call walleminol A, has been partially characterized by mass spectroscopy, nuclear magnetic resonance, ultraviolet and infrared spectroscopy. It can be provisionally interpreted as a tricyclic dihydroxy compound, C15H24O2, with structural features characteristic of a sesquiterpene with an isolated double bond, but further work is required to characterize this compound unequivocally. The minimum inhibitory dose of walleminol A in the bioassays is approximately 50 micrograms/ml, which is comparable with a number of mycotoxins such as citrinin and penicillic acid.
1544Biosynthesis of cytochalasans. XI. New results on the incorporation of phenylalanine into cytochalasin D by Zygosporium masonii [1]. Hadener A, Roth P, Tamm C. Z Naturforsch [C]. 1989 Jan-Feb;44(1-2):19-32.Incorporation of L-[2-2H]phenyl-[2-2H]alanine and L-phenyl-[2-13C, 15N]alanine into cytochalasin D by Zygosporium masonii involved the complete loss of both the alpha-2H- and the alpha-15N-atom. Incorporation of a mixture of L-phenyl-[15N]alanine and L-[U-14C]phenylalanine into cytochalasin D and protein amino acids (phenylalanine, leucine, isoleucine) was accompanied by a substantial loss of 15N with respect to 14C. These effects are attributed to rapid exchange reactions taking place while L-phenylalanine is part of the intracellular pool of amino acids. In addition, the medium- and concentration-dependent incorporation of the carbon skeleton of exogeneous D-phenylalanine into cytochalasin D is reported. In a peptone-based complex medium, D-phenyl-alanine is poorly incorporated. Throughout the whole concentration range (0-250 mg/l), the incorporation rates are less than 10% of those of L-phenylalanine. In a minimal medium containing NH4NO3 as nitrogen source however, D-phenylalanine is preferred over the natural enantiomer by a factor of 1.28 up to 6.78, depending on the concentrations of exogeneous D- and L-phenylalanine. These effects are attributed to the medium-dependent activities of different amino acid transport systems responsible for the uptake of D- and L-phenylalanine in Z. masonii.
1545Zygosporin A, a new antibiotic from Zygosporium masonnii. Hayakawa S, Matsushima T, Kimura T, Minato H, Katagiri K. J Antibiot (Tokyo). 1968 Aug;21(8):523-4. 
1546Studies on the metabolites of Zygosporium masonii. I. Structure of zygosporin A. Minato H, Matsumoto M. J Chem Soc [Perkin 1]. 1970;1:38-45. 
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