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Chaetoglobosin A is a complex macrocyclic alkaloid with potent antimycotic, antiparasitic and antitumor properties. However, the low output and high cost of chaetoglobosin A biosynthesis have hampered the application and commercialization of chaetoglobosin A in agriculture and biomedicine. Here, the CgMfs1 gene, which encodes the major facilitator superfamily secondary transporter, was identified based on bioinformatics analysis, and an intensive study of its effects on chaetoglobosin A biosynthesis and secretion was performed using CgMfs1-silencing and CgMfs1-overexpression strategies. Inactivation of CgMfs1 caused a notable decrease in chaetoglobosin A yield from 58.66 mg/L to 19.95 mg/L (MFS1-3) and 17.13 mg/L (MFS1-4). The use of an efficient expression plasmid in Chaetomium globosum W7 to generate the overexpression mutant OEX13 resulted in the highest chaetoglobosin A increase to 298.77 mg/L. Interestingly, the transcription level of the polyketide synthase gene significantly fluctuated with the change in CgMfs1, confirming that the predicted efflux gene CgMfs1 could play a crucial role in chaetoglobosin A transportation. Effective efflux of chaetoglobosin A could possibly alleviate feedback inhibition, resulting in notable increase in the expression of the polyketide synthase gene. Furthermore, we utilized cornstalk as the fermentation substrate to produce chaetoglobosin A, and scanning electron microscopy and Fourier transform-infrared spectroscopy revealed that the strain OEX13 could well degrade cornstalk, presenting significant increases in the chaetoglobosin A yield, when compared with that produced by the wild-type strain (from 40.32 to 191.90 mg/L). Thus, this research provides a novel analogous engineering strategy for the construction of high-yielding strain and offers new insight into large-scale chaetoglobosin A production.

Chemical investigation on the deep-sea-derived fungus Chaetomium globosum led to the isolation of nine compounds. By extensive analyses of the1D and 2D NMR as well as HRESIMS spectra, their structures were elucidated as xylariol A ( 1 ), 1,3-dihydro-4,5,6-trihydroxy-7-methyl-isobenzofuran ( 2 ), epicoccone B ( 3 ) epicoccolide B ( 4 ), chaetoglobosin G ( 5 ), chaetoglobosin Fex ( 6 ), cochliodone A ( 7 ), cochliodone B ( 8 ), and chaetoviridin A ( 9 ), assorting as four phenolics ( 1 - 4 ), two cytochalosans ( 5 - 6 ), and three azaplilones ( 7 - 9 ). Compounds 1 - 3 were firstly reported from C. globosum . Under the concentrations of 20 μg/mL, 1 , 2 , and 3 exhibited potent in vitro anti-HIV activity with the inhibition rates of 70%, 75%, and 88%, respectively.

The fungus Chaetomium sp. is a causative agent of infections in humans and is ubiquitous in the natural environment. The secondary metabolites of this genus exhibit many biological activities, including antifungal activity and toxicity in mitochondria. In this study, we isolated cristazine from the fungus C. cristatum, which has the potential to inhibit the growth of human epidermoid carcinoma (A431) cells in a dose- and time-dependent manner. Its inhibitory activity was examined using a cell viability assay and cell death was elucidated by western blot analysis. Cristazine triggered apoptotic cell death via the Type I death receptor pathway including the activation of caspases and other target proteins. However, cristazine did not have any effect on mitochondrial apoptotic proteins such as Bid, cytochrome c, and apoptosis-inducing factor. Cristazine inhibited the cell cycle progression by arresting the G1 /S phase and up-regulating the inhibitory proteins of cyclin-dependent kinases. Thus, cristazine has great potential for inducing apoptosis in A431 cells via both cell cycle arrest and the inhibition of cell growth.

The microbial production of dextranase using cheap carbon sources is beneficial to solve the economic loss caused by the accumulation of dextran in syrup. A food-grade microbial cell factory was constructed by introducing the dextranase encoding gene DEX from Chaetomium gracile to the chromosome of Bacillus subtilis, and the antibiotic resistance marker gene was subsequently deleted via the Cre/loxP strategy. The dual-promoter system with a sequentially arranged constitutive P43 promoter resulted in an 85 % increase in DEX expression. Under the optimal fermentation conditions of 10 g/L maltose, 15 g/L casein, 1 g/L Na2 HPO4 , 1 g/L FeSO4 and 8 g/L NaCl, DEX activity was increased from 2.625 to 64.34 U/mL. Recombinant DEX was purified 5.98-fold with a recovery ratio of 26.67 % and specific activity of 3935.02 U/mg. Enzyme activity was optimal at 55 °C and pH 5.0 and remained 80.34 % and 71.36 % of the initial activity at 55 °C and pH 4.0 after 60 min, respectively. The enzyme possessed high activity in the presence of Co2+ , while Ag+ showed the strongest inhibition ability. The optimal substrate was 20 g/L dextran T-2000. The findings could facilitate the low-cost, large-scale production of food-grade DEX for use in the sugar industry.

Rationale Microbial natural products are often biosynthesized as classes of structurally related compounds that have similar tandem mass spectrometry (MS/MS) fragmentation patterns. Mining MS/MS datasets for precursor ions that share diagnostic or common features enables entire chemical classes to be identified, including novel derivatives that have previously been unreported. Analytical data analysis tools that can facilitate a class-targeted approach to rapidly dereplicate known compounds and identify structural variants within complex matrices would be useful for the discovery of new natural products. Methods A diagnostic fragmentation filtering (DFF) module was developed for MZmine to enable the efficient screening of MS/MS datasets for class-specific product ions(s) and/or neutral loss(es). This approach was applied to series of the structurally related chaetoglobosin and cytochalasin classes of compounds. These were identified from the culture filtrates of three fungal genera: Chaetomium globosum, a putative new species of Penicillium (called here P. cf. discolor: closely related to P. discolor), and Xylaria sp. Extracts were subjected to LC/MS/MS analysis under positive electrospray ionization and operating in a data-dependent acquisition mode, performed using a Thermo Q-Exactive mass spectrometer. All MS/MS datasets were processed using the DFF module and screened for diagnostic product ions at m/z 130.0648 and 185.0704 for chaetoglobosins, and m/z 120.0808 and 146.0598 for cytochalasins. Results Extracts of C. globosum and P. cf. discolor strains revealed different mixtures of chaetoglobosins, whereas the Xylaria sp. produced only cytochalasins; none of the strains studied produced both classes of compounds. The dominant chaetoglobosins produced by both C. globosum and P. cf. discolor were chaetoglobosins A, C, and F. Tetrahydrochaetoglobosin A was identified from P. cf. discolor extracts and is reported here for the first time as a natural product. The major cytochalasins produced by the Xylaria sp. were cytochalasin D and epoxy cytochalasin D. A larger unknown "cytochalasin-like" molecule with the molecular formula C38 H47 NO10 was detected from Xylaria sp. culture filtrate extracts and is a current target for isolation and structural characterization. Conclusions DFF is an effective LC/MS data analysis approach for rapidly identifying entire classes of compounds from complex mixtures. DFF has proved useful in the identification of new natural products and allowing for their partial characterization without the need for isolation.

Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less‐activated hydrocarbons, by transferring peroxide‐borne oxygen. We investigated a cell‐free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg−1. Although the well‐known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5‐epoxide of testosterone in β‐configuration and 16α‐hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

One natural p-terphenyl glycoside, gliocladinin C, and two furano-polyene derivatives, chaetominins A and B, were isolated from potato endophytic fungus Chaetomium subaffine. The absolute configurations of these compounds were elucidated by HR-ESI-MS, NMR, the DP4+ probabilities and electronic circular dichroism (ECD) spectra. Furthermore, gliocladinin C and chaetominin A showed cytotoxic activity against two selected human tumor cell lines (Hep-2 and HepG-2).

Two new azaphilone derivatives, chaephilones A (1) and B (2), were isolated from the fungus Chaetomium globosum, together with four structurally related analogs 3 - 6. The structures of 1 and 2 were elucidated by comprehensive spectroscopic analyses including HR-ESI-MS and NMR. The known compounds were identified as chaetomugilin Q (3), chaetomugilin D (4), 11-epichaetomugilin A (5), and chaetomugilin S (6) by comparing their NMR data and optical rotation values with those reported. Compound 2 represents the first example of azaphilone with an open furan ring. Compounds 1 and 2 were evaluated for cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) by the MTS method.

This study aims at characterisation of the impact of Chaetomium globosum on copper stress resistance of maize seedlings. Higher levels of copper treatment decreased maize dry weight and induced a marked increase in osmotic solutes, antioxidant enzyme activity and the level of lipid peroxidation. On the other hand, addition of the endophytic C. globosum alleviated the toxic effect of copper on maize growth. The combination of copper sulphate and Chaetomium increased seedling dry weight, osmotic solute content and antioxidant enzyme activity compared to copper sulphate alone, while lipid peroxidation levels were also decreased. The fungal scavenger system might be important for supporting the ability of maize seedlings to resist copper toxicity.

This study was carried out to improve our understanding of the diversity and decomposition potential of endophytes in the leaves of Cinnamomum camphora trees grown in a subtropical region of China. We isolated and identified endophytic fungi from senescent leaves of C. camphora and tested their role in decomposition through pure-culture and pre-colonization. A total of 2,861 endophytic fungi isolated from 69 leaves of C. camphora were grouped into 39 taxa comprising 36 Ascomycetes and 3 Basidiomycetes based on sporulation and ITS sequence analysis. Of these, Colletotrichum gloeosporioides was the most common species (69% relative abundance and 96% colonization frequency), followed by Cladosporium sp.1, Colletotrichum sp. and Chaetomium sp. All 39 endophytes had the ability to decompose C. camphora leaf litter in pure culture, and a few exhibited >20% litter mass loss in 2 months. In most cases, single endopyhytic species showed lower mass loss than mixed microbial groups from active soil after 60 or 120 days. In pre-inoculation, endophytic fungi like Chaetomium sp., Cladosporium sp.1, C. gloeosporioides, Colletotrichum sp. and Guignardia sp. exhibited higher abundance and caused greater mass loss, indicating the potential of these groups to enter and significantly accelerate the process of decomposition. This study concludes that, after entering the decomposition process, selected endophytic fungi with high abundance could influence significantly the decomposition process and thus probably affect carbon and nutrient cycling in C. camphora plantations.

Cellobiose dehydrogenase (CDH) is an extracellular fungal flavocytochrome specifically oxidizing cellooligosaccharides and lactose to corresponding (-lactones by a variety of electron acceptors. In contrast to basidiomycetous CDHs, CDHs of ascomycetes also display certain activity toward glucose. The objective of this study was to establish the structural reasons of such an activity of CDH from mesophilic ascomycete Chaetomium sp. INBI 2-26 (ChCDH). The complete amino acid sequence of ChCDH displayed high levels of similarity with the amino acid sequences of CDHs from the thermophilic fungi Thielavia heterotallica and Myriococcum thermophilum. Peptide mass fingerprinting of purified ChCDH provided evidence for the oxidation of methionine residues in the FAD-domain. Comparative homology modeling of the structure of the ChCDH FAD-domain in complex with the transition state analog based on the structure of the same complex of basidiomycetous CDH (1NAA) as template indicated possible structural reasons for the enhanced activity of ascomycetous CDHs toward glucose at neutral pH, which is a prerequisite for application of CDH in a variety of biocompatible biosensors and biofuel cells.

The fungal community of six sand samples from Saudi Arabia and Jordan deserts was characterized by culture‐independent analysis via next generation sequencing of the 18S rRNA genes and by culture‐dependent methods followed by sequencing of internal transcribed spacer (ITS) region. By 18S sequencing were identified from 163 to 507 OTUs per sample, with a percentage of fungi ranging from 3.5% to 82.7%. The identified fungal Phyla were Ascomycota, Basal fungi, and Basidiomycota and the most abundant detected classes were Dothideomycetes, Pezizomycetes, and Sordariomycetes. A total of 11 colonies of filamentous fungi were isolated and cultured from six samples, and the ITS sequencing pointed toward five different species of the class Sordariomycetes, belonging to genera Fusarium (F. redolens, F. solani, F. equiseti), Chaetomium (C. madrasense), and Albifimbria (A. terrestris). The results of this study show an unexpectedly large fungal biodiversity in the Middle East desert sand and their possible role and implications on human health.

A CE method is described for the enantioselective analysis of propranolol (Prop) and 4-hydroxypropranolol (4-OH-Prop) in liquid Czapek medium with application in the study of the enantioselective biotransformation of Prop by endophytic fungi. The electrophoretic conditions previously optimized were as follows: an uncoated fused-silica capillary, 4% w/v carboxymethyl-β-CD in 25 mmol/L triethylamine/phosphoric acid (H₃PO₄) buffer at pH 9 as running electrolyte and 17 kV of voltage. UV detection was carried out at 208 nm. Liquid-liquid extraction using diethyl ether: ethyl acetate (1:1 v/v) as extractor solvent was employed for sample preparation. The calibration curves were linear over the concentration range of 0.25-10.0 μg/mL for each 4-OH-Prop enantiomer and 0.10-10.0 μg/mL for each Prop enantiomer (rgreater-than-or-equal0.995). Within-day and between-day relative standard deviations and relative errors for precision and accuracy were lower than 15% for all the enantiomers. Finally, the validated method was used to evaluate Prop biotransformation in its mammalian metabolite 4-OH-Prop by some selected endophytic fungi. The screening of five strains of endophytic fungi was performed and all of them could biotransform Prop to some extent. Specifically, Glomerella cingulata (VA1) biotransformed 47.8% of (-)-(S)-Prop to (-)-(S)-4-OH-Prop with no formation of (+)-(R)-4-OH-Prop in 72 h of incubation.

Zusammenfassung Da das Absterben kleiner Termiten-Kolonien, besonders nach einem Umsetzen in neue Umgebung, mit der Wirkung von Schimmelpilzen in Zusammenhang gebracht wurde, andererseits gewisse Schimmelpilzarten als zusatzliche Nahrung fur die Termiten von Wert sind, wurde der Einflus von rund 20 Ascomycetes-Arten und rund 10 Fungi imperfecti, zum Teil mit mehreren (bis zu 9) Stammen, so das insgesamt uber 60 Pilze benutzt wurden, auf Kalotermes flavicollis (Fabr.), Heterotermes indicola (Wasmann), Reticulitermes lucifugus (Rossi) var. santonensis Feytaud und Nasutitermes ephratae (Holmgren) gepruft. Dabei wurden Sporen, Mycel oder beides an einheitliche Gruppen der Termiten bei gleichbleibenden Temperatur- und Feuchtigkeits-bedingungen verfuttert. Zum Vergleich dienten entsprechende Gruppen ohne jede Nahrung oder mit Filtrierpapier-Futterung. Die Wirkung der einzelnen Schimmelpilzarten und -stamme auf die Termiten reicht von starker Giftigkeit, die zum Absterben aller Tiere im Laufe weniger Tage fuhren kann, bis zu Nutzlichkeit als Nahrungsstoff, bei dem die Tiere langer am Leben bleiben als bei Filtrierpapier-Futterung. Solche Unterschiede wurden nicht nur bei verschiedenen Pilzarten, sondern auch bei den untersuchten Stammen einer Art gefunden. Die verwendeten Termitenarten reagierten nur bei einem Teil der Pilze gleichsinnig. In vielen Fallen verhielten sie sich verschieden. Trichoderma-Arten wirken meist giftig auf Termiten. Aspergillus flavus enthalt sehr giftige, indifferente und ausgesprochen forderliche Stamme. Andere Aspergillus- und mehrere Penicillium-Arten zeigten sehr verschiedenen Einflus. Ausgesprochen gunstig verhielten sich die gepruften Stamme von Aspergillus ustus, Alternaria humicola, Chaetomium-Arten, Dactylium fusarioides, Memnoniella echinata und Trichurus spec., also besonders Cellulose abbauende sogenannte ”Moderfaule„-Pilze. Die Ursachen der verschiedenen Giftigkeit und des unterschiedlichen Verhaltens der Termitenarten sollten durch weitere Versuche, bei denen Toxin-und Antibiotica-Wirkung und die Symbionten-Zusammensetzung bei den Termitenarten zu beachten waren, erforscht werden. Summary The dying of small termite colonies, especially after transfer into a new environment, has been attributed to the action of mould fungi; but on the other hand certain moulds are useful as additional food for the termites. Therefore the influence of about 30 species of Ascomycetes and some Fungiimperfecti, partly represented by several (up to 9) strains, altogether of more than 60 fungus cultures, on Kalotermes flavicollis (Fabr.), Heterotermes indicola (Wasmann), Reticulitermes lucifugus (Rossi) var. santonensis Feytaud, and Nasutitermes ephratae (Holmgren) was tested. Uniform groups of termites were fed with spores, mycelium, or both combined, under constant conditions of temperature and moisture. Equivalent groups, kept without any food or on filter paper, were used as controls. The effect of the individual species and strains of moulds on the termites ranges from strong toxicity, causing death of all specimens within a few days, to usefulness as a nutriment which effects longer survival of the termites than filter paper. This variation was not only stated among different species of fungi, but also among the tested strains of one species. The termite species used reacted only with part of the fungi equally. In many cases they showed different behaviour. Trichoderma species are mostly toxic towards termites. Aspergillus flavus has highly toxic, indifferent, and markedly favourable strains. Other species of Aspergillus and several species of Penicillium varied considerably in their effect. Markedly favourable influence was stated with the tested strains of Aspergillus ustus, Alternaria humicola, Chaetomium spec., Dactylium fusarioides, Memnoniella echinata, and Trichurus spec.; most are especially cellulose-decomposing species, so-called ”soft-rot„ fungi. The causes of the varying toxicity and of the different behaviour of termite species should be investigated by further tests, taking the effect of toxins and antibiotics and the composition of symbionts with the respective termites into consideration.

As part of the effort to find better cellulases for bioethanol production processes, we were looking for novel GH‐7 family cellobiohydrolases, which would be particularly active on insoluble polymeric substrates and participate in the rate‐limiting step in the hydrolysis of cellulose. The enzymatic properties were studied and are reported here for family 7 cellobiohydrolases from the thermophilic fungi Acremonium thermophilum, Thermoascus aurantiacus, and Chaetomium thermophilum. The Trichoderma reesei Cel7A enzyme was used as a reference in the experiments. As the native T. aurantiacus Cel7A has no carbohydrate‐binding module (CBM), recombinant proteins having the CBM from either the C. thermophilum Cel7A or the T. reesei Cel7A were also constructed. All these novel acidic cellobiohydrolases were more thermostable (by 4–10°C) and more active (two‐ to fourfold) in hydrolysis of microcrystalline cellulose (Avicel) at 45°C than T. reesei Cel7A. The C. thermophilum Cel7A showed the highest specific activity and temperature optimum when measured on soluble substrates. The most effective enzyme for Avicel hydrolysis at 70°C, however, was the 2‐module version of the T. aurantiacus Cel7A, which was also relatively weakly inhibited by cellobiose. These results are discussed from the structural point of view based on the three‐dimensional homology models of these enzymes.

Linen is the most historical Egyptian textile fibre liable to fungal deterioration. Fungal deterioration of dyed linen textiles may appear as undesirable different stains. In order to success in removing of fungal stains from biodeteriorated historical Egyptian dyed linen textiles, it is necessary to understand the nature and causes of these stains, hence their subsequent removal. So this paper aims to investigate the effect of fungi on dyed linen textiles. In this study linen textile samples were experimentally dyed by two different dyes, blue one as an example to vat dye and yellow one as an example to direct dye. This work is done on two of the most important dyes (Turmeric and indigo), which were popular in most of historical periods in Egypt. Dyed linen samples were experimentally biodegraded by thirty different fungal strains isolated previously from historical Egyptian linen samples. The produced change in colours of the biodeteriorated samples was detected visually. Also, the change in reflection spectra and colour differences produced to dyed linen textiles after fungal deterioration, were assessed and evaluated by using spectrophotometer. This study reported that most of tested fungi contribute to discoloration of all tested dyed linen samples. These results indicate that most of stains on historical Egyptian dyed linen textiles, may be fungal stains. The results confirm that undyed linen textiles more liable to fungal biodeterioration than dyed ones. Also the results show that yellow dyed linen textiles are more susceptible to fungal deterioration than blue dyed linen textiles. The obtained results show that Alternaria tenuissima, Chaetomium globosum, Chaetomium sp., Penicillium raistrickii, P. soppi, P. asperum, P. citrinum, Aspergillus carbonarius, A. fischeri, A. nidulans, A. terreus and A. niger, had showed the maximum colour changes of the deteriorated yellow dyed linen samples. The results also show that Alternaria tenuissima, Chaetomium sp., Penicillium asperum, P. citrinum, Aspergillus nidulans and A. spinulosus, had shown the maximum colour changes of the deteriorated blue dyed linen samples.

The interaction between endophytic biocontrol agent Chaetomium spirale ND35 and the soil-borne plant pathogen Rhizoctonia solani was studied by light microscopy and transmission electron microscopy (TEM), as well as further investigated by gold cytochemistry to assess the potential role of cell wall degrading enzymes (CWDEs) during the mycoparasitic process. Macroscopic observations of fungal growth in dual cultures revealed that pathogen growth inhibition occurred soon after contact with the antagonist, followed by the overgrowth of C. spirale on the colony of R. solani. The coiling of C. spirale around R. solani and intracellular growth of the antagonist in its host occurred frequently. Moreover, in advanced stage of interaction between the antagonist and the pathogen, The growth and development of C. spirale were associated with highly morphological changes of the host fungal cell, characterized by retraction of plasma membrane and cytoplasm disorganization. Further, TEM investigations through localization by gold immunocytochemistry showed that contact between the two fungi was mediated by an amorphous ß-1,3-glucan-enriched matrix originating from cell wall of the antagonist C. spirale and sticking to its host surface. At the same time, the hemispherical wall appositions which were intensely labeled by the antibodies of ß-1, 3-glucan in cell wall of R. solani were induced to form at sites of potential antagonist entry. However, the antagonist was capable of penetrating this barrier, indicating that ß-1,3-glucanases were produced during the mycoparasitic process. Localization of N-acetylglucosamine residues (chitin) with the gold-labelled wheat germ agglutinin (WGA) implicated that chitinases might be involved in the CWD of R. solani in this antagonistic process as well. This report is the first evidence about mechanisms of the interactions between C. spirale and R. solani in ultrastructural and cytochemical aspects.

The crystal structures of thermophilic xylanases from Chaetomium thermophilum and Nonomuraea flexuosa were determined at 1.75 and 2.1 A resolution, respectively. Both enzymes have the overall fold typical to family 11 xylanases with two highly twisted beta-sheets forming a large cleft. The comparison of 12 crystal structures of family 11 xylanases from both mesophilic and thermophilic organisms showed that the structures of different xylanases are very similar. The sequence identity differences correlated well with the structural differences. Several minor modifications appeared to be responsible for the increased thermal stability of family 11 xylanases: (a) higher Thr : Ser ratio (b) increased number of charged residues, especially Arg, resulting in enhanced polar interactions, and (c) improved stabilization of secondary structures involved the higher number of residues in the beta-strands and stabilization of the alpha-helix region. Some members of family 11 xylanases have a unique strategy to improve their stability, such as a higher number of ion pairs or aromatic residues on protein surface, a more compact structure, a tighter packing, and insertions at some regions resulting in enhanced interactions.

Onychomycosis is one of the most common infections of the nail. It can be caused by dermatophytes, Candida species and other fungi. Although moulds can cause onychomycosis, they account for a minority of cases, mainly great toenail onychomycosis. We describe a case of an 11-year-old girl who developed an onychomycosis by Chaetomium species in second and third toenails.

We used electrochemical impedance spectroscopy (EIS) to investigate microbial degradation of polyimides used as insulators in electronic packaging. The microbial inoculum was a fungal consortium isolated from degraded polyimides. Microorganisms grew on these polymers yielding distinctive EIS spectra indicative of failure. Degradation appeared to occur in a number of steps. Two distinctive stages in the decline of film resistance were observed in the inoculated EIS cells within 17 and 72 days after inoculation. The early stage of resistance decrease may be related to the ingress of water molecules and ionic species into the polymeric materials, whereas the second stage probably resulted from partial degradation of the polymers by fungal growth on the polymer film. The active fungal consortium was comprised of Aspergillus versicolor, Cladosporium cladosporioides, and a Chaetomium species. All of these fungi are common environmental contaminats. The relationship between changes of impedance spectra and microbial degradation of the coatings was supported by scanning electron microscopic observations of fungi on the surface of the inoculated polyimides. Our data indicate that the insulating polyimides used in electronic applications are susceptible to fungal degradation under appropriate environmental conditions, particularly in the presence of moisture. © 1996 John Wiley & Sons, Inc.

Chaetocin, a natural product isolated from fungi of Chaetomium species, is a mem- ber of the epipolythiodiketopiperazines (ETPs), which have various biological activities, including cytostatic and anticancer activities. Recently, the inhibitory activity toward histone methyltransferases (HMTs) was discovered for chaetocin. We previously reported the first total synthesis of chaetocin and various derivatives. During studies on the structure-activity relationship for HMT inhibition, we found that the enantiomer of chaetocin (ent-chaetocin) is a more potent apoptosis inducer than natural chaetocin in human leukemia HL-60 cells. Mechanistic studies showed that ent-chaetocin induces apoptosis through the caspase- 8/caspase-3 pathway.

Precursor-fed cultivation of endophytic Chaetomium globosum1C51 afforded nine novel “unnatural” halogenated chaetoglobosins including those with more preferable immunosuppressive activity.

Chaetomugilins G and H were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish, Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, and chemical transformation. In addition, the absolute configuration of chaetoviridin C was established by derivatization from chaetomugilin A. These compounds exhibited a growth inhibitory activity against cultured P388, HL-60, L1210 and KB cells.

Chaetomugilins A∼F have been isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, some chemical transformations and an X-ray analysis. These compounds exhibited significant growth inhibition against cultured P388 cells and HL-60 cells. In addition, chaetomugilins A, C and F showed selective cytotoxic activities against 39 human cancer cell lines.

A marine fungal isolate, identified as Chaetomium sp., was cultivated and found to produce a novel benzonaphthyridinedione derivative, chaetominedione (1). In addition to the known fungal metabolites, 2-furancarboxylic acid (2) and 5-(hydroxymethyl)-2-furancarboxylic acid (3) were obtained. The structures of all the compounds were determined based on extensive spectroscopic measurements (1D and 2D NMR, MS, UV, and IR). The total extract and compound 1 had significant inhibitory activity toward p56lck tyrosine kinase (18.7% and 93.6% enzyme inhibition at 200 μg/mL, respectively).

SUMMARY Fungi were isolated from soybean plants in ten fields in south-west France. Correspondence analysis (COA) was used to find associations among taxa (species, genera, groups) and sampling units (i.e. one field at one sampling date). The first axis of the COA demonstrated a dominant sampling date effect; the second indicated an association among certain sampling units and specific taxa. Regression analysis of COA coordinate values indicated that fields with high relative isolation frequencies of Fusarium spp., F. oxysporum and ‘other species’ (mostly Chaetomium spp. and sterile fungi) were characterised by greater plant fresh weight and nodule number and lower ratings for root necrosis. Cylindrocarpon spp., Cephalosporium spp. and F. solanihad high relative isolation frequencies in fields with lower plant weight, lower nodule number and higher root necrosis ratings. The relative importance of fungal taxa was also related to soil type.

Chaetomugilins A–C were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques, some chemical transformations, and an X-ray analysis. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.

Examination of cottonseed production has shown that boll weevils (Anthonomus grandis), boll rots, and improper handling and storage conditions are critical factors inAspergillus flavus contamination of cotton-seed.A. flavus cultures were isolated from both field-collected and laboratory emerged boll weevils, as well as from boll weevil emergence holes. Diseased cotton bolls have been found to containA. flavus conidia. Infection byA. flavus was limited to the surface of cottonseeds collected from gin and from the gin blower. Seeds improperty stored outside the gin were infected internally withA. flavus. Observation of bright greenish-yellow fluorescence was not useful as a diagnostic procedure to detect contaminated seeds. Aflatoxin-producing potential ofA. flavus isolates is being investigated. WhenA. flavus conidia were artifically inoculated onto the surface of the seeds, 87% of the seeds from Athens, GA, were internally infected whereas only 29% of the seeds from Macon, GA, were internally infected.A. flavus invade the cottonseed embryo through the chalazal region, the micropylar region, or cracks developed in the seed coat during ginning. Invasion of cottonseed byA. flavus was predominant at 28, 30, and 37 C while at 15 and 20 C other fungi dominated in surface and internal invasions of cottonseed. At relative humidities of 75% and 80%,Chaetomium spp. successfully competed in growth on the surface, while at a relative humidity of 90% and above, fungi belonging to the orderMucorales outgrewA. flavus.

Mouse embryo limb bud (LB) and midbrain (MB) cells were prepared from day 10 mouse embryos and cultured as micromass cell islands for 5 days. Differentiation was determined by the number of stainable foci of differentiated cells, and the concentration at which each compound inhibited the formation of differentiated foci by 50% of the control value (IC50) was estimated according to the method by Flint and Orton (1984). The values of IC50 of L-dopa, which is known as a teratogen, were 24 μig/ml in LB cultures and 12 μ/ml in MB cultures, respectively. Teratogenic hazards of three mycotoxins were compared in this system. Chaetochromin A and chaetochromin D, which were new naphtho-γ-pyrone dimers produced by Chaetomium sp., indicated strong inhibition (IC50 0.13-0.24 μ/ml) in LB and MB cell cultures, and ustilaginoidin A, which was a naphtho-γ-pyrone dimer produced by Ustilaginoidea virens, inhibited at higher concentration than chaetochromins by several-folds in LB and MB cultures.

Zusammenfassung: Seren von 183 Kranken (Myelosis leucaemica acuta 82, Myelosis leucaemica chronica 28, Lymphadenosis leucaemica chronica 16, Lymphoma malignum 39, Aplasia medullae ossium et granulocyto penia 18) und 26 Kontrollpersonen wurden untersucht auf das Vorkommen von Prazipitinen gegen Antigene aus 22 Pilzarten (Aspergillus, Penicillium, Mucor, Rhizopus, Fusarium, Cladosporium, Stemphylium, Scopulariopsis, Syncephalastrum, Chaetomium, Candida, Geotrichum, rhodotorula). Bei neoplastischen Krankheiten konnten sehr hafig Immunreaktionen, besonders auf Antigene aus Aspergillus, Mucor und Rhizopusarten nachgewiesen werden. Bei der Atiopathogenese von Blutkrankheiten wird die Rolle von Kontakten mit toxigenen Pilzen betont. Summary: Sera from 183 hematologic patients (myelosis leucaemica acuta 83, myelosis leucaemica chronica 28, lymphadenosis leucaemica chronica 16, lymphoma malignum 39, aplasia medullae ossium et granulocytopenia 18) and 26 control persons were studied for the presence of precipitins against 22 fungal genera (Aspergillus, Penicilllum, Mucor, Rhizopus, Fusarium, Cladosporium, Stemphylium, Scopulariopsis, Syncephalastrum, Chaetomium, Candida, Geotrichum, Rhodotorula). In neoplastic diseases, frequent immune responses, aspecially against antigens from Aspergillus, Mucor and Rhizopus genera were demonstrated. In the etiopathology of blood diseases the role of contacts with toxicogenic fungi is stressed.

Using four medium types (glucose-, cellulose-, 50% sucrose- and 10% NaCl-Czapek's agar), it was possible to isolate 15 fungal genera, 78 species and 6 varieties. The collective fungal spectrum varied from one medium to another where the highest number of species (57 species/1000 seeds) was obtained on glucose- and the lowest (31 species/1000 seeds) on 10% NaCl-Czapek's agar. Aspergillus, Penicillium, and sometimes Rhizopus and Chaetomium were the most common genera on the different medium types. The most common fungal species especially on glucose- and cellulose-Czapek's agar were, Aspergillus niger, A. flavus, A. ochraceus, A. fumigatus, A. flavus var. columnaris, Penicillium chrysogenum, Rhizopus stolonifer and Chaetomium globosum. Members of A. glaucus group were more frequently recovered on 10% NaCl- and 50% sucrose-Czapek's agar.

The structure and absolute configuration of Chaetocin, a metabolite of the fungus Chaetomium minutum with antibacterial and cytostatic activity has been elucidated by chemical and X-ray methods.

Tomato roots with brown root rot showed three types of lesion: cortical rot of fine roots, ‘corky root’, and basal stem rot. The fungi most commonly isocated from diseased roots were: Colletotrichum atramentarium, Chaetomium spp., Cephalosporium spp., Volutella ciliata, and a grey mycelial fungus sometimes producing pycnidia (Pyrenochaeta sp.). Other fungi isocated less frequently were: Myrothecium roridum, Petriella asymmetrica, Trichoderma airide, Phytophthora spp., Alternaria sp. and Fusarium spp. There were differences between the numbers of each species isocated from the three types of lesion in steamed and in unsteamed soils, and some seasonal variation. Inoculation experiments with seedlings in vitro showed that Ckaetomium cochliodes and Petriella asymmetrica could infect radicles. On older plants growing in soil Colletotrichum atramentarium was the only effective pathogen. Culture filtrates from C. atramentarium, Chaetomium cochliodes, and P. asymmetrica decreased root growth when tested in vitro. Leachates from loam and a loam-manure mixture decreased the growth of tomato root-tip cultures; the effect of these leachates was altered by autoclaving.

SUMMARY Specific ATP-phosphotransferases for glucose, fructose and mannose, and glucosephosphate and mannosephosphate isomerases have been extracted from Chaetomium globosum. The fructokinase is stabilized by potassium whereas the glucokinase is activated by this cation, but is, otherwise, more stable than the former. The less-studied mannokinase showed no requirement for potassium. The inhibition of the fructokinase by glucose and mannose, and of the glucokinase by mannose are detailed, together with pH optima, Km values and other properties of the enzymes. The level of glucosephosphate isomerase was found to be higher in fructosegrown than in glucose-grown mycelium. The role of the enzyme systems in the absorption and utilization of exogenous hexoses is discussed.

A B S T R A C T Development of perithecia from single, uninucleate ascospores disclosed a homothallic condition for Chaetomium erraticum. This species was found to produce sessile ascogonial coil initials from uninucleate vegetative cells that become enveloped by hyphae formed at the base of the ascogonium. The ascogonium consists of several cells that are uninucleate or binucleate. A perithecium forms from numerous divisions and enlargement of the surrounding uninucleate cells. Differentiation of the perithecial cells results in the formation of a carbonaceous wall, perithecial hairs, and an ostiole lined with periphyses. A convex hymenial cluster of ascogenouis cells forms in the lower half of the centrum from which typical croziers develop. Asci push up into the pseudoparenchyma cells of the centrum. The growth of the ascogenous system is in part responsible for increase in perithecial size. The breakdown of the pseudoparenchyma cells around the developing asci results in the formation of a central cavity in which ascospores are released when the asci deliquesce. No paraphyses are present. The type of development and features of the centrum of C. erraticum and other species of Chaetomium indicate a distinct Xylaria-type centrum. SPECIES belonging to the genus Chaetomium K-unze have been grouped taxonomically primnarily on the characteristics of size and shape of perithecia, terminal hairs, and ascospores (Skolko and Groves, 1953; Udagawa, 1960; Ames, 1961). These characteristics are useful in determining species but may not indicate true taxonomic relationships. The use of ascus type and centrum morphology should offer more useful criteria in establishing relationships among species of this genus. Most studies dealing with morphology of the genus Chaetomium have been concerned with the initial stages of the ascogonium. Detailed structure of the centrum has been studied only in C. globosum Kunze ex Fries (Oltmanns, 1887; Whiteside, 1961), C. spirale Zopf (Dangeard, 1907), C. elatum Kunze ex Fries (Moreau and Moreau, 1954), C. brasiliense Batista and Pontual (Whiteside, 1957

Forty-seven isolates representing twenty-seven species of Chaetomium were tested for their ability to control seedling blight of oat seedlings caused by Fusarium spp., chiefly F. nivale (Fr.) Ces. In pot tests the majority of the isolates were ineffective, but certain isolates of Chaetomium cochliodes Pall, and C. globosum Kunze gave a large measure of control and were as effective as an organic mercury seed dressing. Control of disease was also obtained when living material was attached to the surface of oat seed and when infested seed was soaked in cell-free filtrates from cultures of isolates which reduced disease in vivo. Substantial control of disease was obtained when infested seed was sown in soil to which cultures of C. cochliodes had been added 10 months previously. This antagonist was able to grow through unsterile soil in the presence of certain added substrates. The results of pot experiments were confirmed in field experiments. Isolates of Chaetomium which controlled disease in pot and field experiments were not strikingly antagonistic to Fusariirm nivale in pure culture on agar media.

Patients with acute leukemia are susceptible to a variety of opportunistic infections. A patient with acute lymphocytic leukemia who developed a Chaetomium-caused empyema, which may have subsequently contributed to his death is reported.