Search

Five new xanthoquinodins, A4-A6 (1-3), B4 (4), and B5 (5), were isolated from the crude extract of the endolichenic fungal strain Chaetomium elatum (No. 63-10-3-1), along with three known xanthoquinodins, A1-A3 (6-8). Their structures were determined by detailed spectroscopic analysis and comparison of the NMR data with those of the closely related compounds previously reported. The absolute configuration of 1 was established by X-ray crystallographic analysis and ECD calculation. The cytotoxic activity of all compounds was tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines.

Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In eukaryotes, the nucleocytoplasmic transport of macromolecules is mainly mediated by soluble nuclear transport receptors of the karyopherin-β superfamily termed importins and exportins. The highly versatile exportin chromosome region maintenance 1 (CRM1) is essential for nuclear depletion of numerous structurally and functionally unrelated protein and ribonucleoprotein cargoes. CRM1 has been shown to adopt a toroidal structure in several functional transport complexes and was thought to maintain this conformation throughout the entire nucleocytoplasmic transport cycle. We solved crystal structures of free CRM1 from the thermophilic eukaryote Chaetomium thermophilum. Surprisingly, unbound CRM1 exhibits an overall extended and pitched superhelical conformation. The two regulatory regions, namely the acidic loop and the C-terminal α-helix, are dramatically repositioned in free CRM1 in comparison with the ternary CRM1-Ran-Snurportin1 export complex. Single-particle EM analysis demonstrates that, in a noncrystalline environment, free CRM1 exists in equilibrium between extended, superhelical and compact, ring-like conformations. Molecular dynamics simulations show that the C-terminal helix plays an important role in regulating the transition from an extended to a compact conformation and reveal how the binding site for nuclear export signals of cargoes is modulated by different CRM1 conformations. Combining these results, we propose a model for the cooperativity of CRM1 export complex assembly involving the long-range allosteric communication between the distant binding sites of GTP-bound Ran and cargo.

Ribosome-associated chaperones act in early folding events during protein synthesis. Structural information is available for prokaryotic chaperones (such as trigger factor), but structural understanding of these processes in eukaryotes lags far behind. Here we present structural analyses of the eukaryotic ribosome-associated complex (RAC) from Saccharomyces cerevisiae and Chaetomium thermophilum, consisting of heat-shock protein 70 (Hsp70) Ssz1 and the Hsp40 Zuo1. RAC is an elongated complex that crouches over the ribosomal tunnel exit and seems to be stabilized in a distinct conformation by expansion segment ES27. A unique α-helical domain in Zuo1 mediates ribosome interaction of RAC near the ribosomal proteins L22e and L31e and ribosomal RNA helix H59. The crystal structure of the Ssz1 ATPase domain bound to ATP-Mg²⁺ explains its catalytic inactivity and suggests that Ssz1 may act before the RAC-associated chaperone Ssb. Our study offers insights into the interplay between RAC, the ER membrane-integrated Hsp40-type protein ERj1 and the signal-recognition particle.

Chaetoconvosins A and B (1 and 2), two novel cytochalasan alkaloids with a new 6/6/5/5/7 pentacyclic ring system, were isolated from the solid-state fermented medium of the wheat rhizospheric fungus Chaetomium convolutum cib-100. Their structures were elucidated on the basis of spectroscopic data. The structure of chaetoconvosin A (1) was confirmed by X-ray crystallographic analysis. Chaetoconvosin B (2), the major metabolite, showed remarkable inhibitory ability on root elongation and moderate cytotoxicity against several cancer cell lines.

Cultivation of Chaetomium mollipilium with nicotinamide, a NAD(+)-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C(13)-polyketides, mollipilin A-E (1-5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1-6, and plausible biosynthetic pathways for 1-7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.

Six new dibenzo[b,e]oxepinone metabolites, chaetones A-F (1-6), as well as three known compounds, 1-hydroxy-6-methyl-8-hydroxymethylxanthone (7), citreorosein (8), and emodin (9), were obtained from a freshwater-derived fungal strain Chaetomium sp. YMF 1.02105. Their structures were established on the basis of extensive spectroscopic data analysis and comparison with spectroscopic data reported. Compounds 1-6 are further additions to the small group of dibenzo[b,e]oxepinones represented by arugosins A-H. Compounds 1-7 were tested for their cytotoxic activities against A549, Raji, HepG2, MCF-7, and HL-60 cell lines. The results showed that compound 3 had significant cytotoxicity with IC50 values of 1.2, 1.8, 1.9, 2.3, and 1.6 µg/mL, respectively, against the five cancer cell lines. All compounds showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538) in standard disk assays., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Morphology of ascomatal hairs was traditionally used as a primary character in the classification of the fungal genus Chaetomium. However, the taxonomic value of ascomatal hair morphology is questioned in modern taxonomy of Chaetomium. Chaetomium indicum and C. funicola are two species proposed only by their differences in ascomatal hairs. The aim of this study is to understand the difference between these two species and their variability in the morphology of ascomatal hairs at the level of protein expression patterns, as well as to ressess the taxonomic value of the ascomatal hairs., Methods: We performed microscopic examination to obtain the morphological characters of the typical and variable strains in both C. indicum and C. funicola. Then we used two-dimensional gel electrophoresis (2DE) to compare the protein expression patterns of the two species, including their typical and variable strains., Results: The comparison of the obtained 2DE maps indicated that C. indicum and C. funicola exhibited species-specific protein expression patterns. The phylogenetic tree derived from the distance matrix of expression patterns with Neighbor-joining algorithm also revealed that the tested strains of C. indicum and C. funicola fell into two distinct clades, among which the variant strains were grouped together with the typical strains of the same species., Conclusion: The consistency of species delimitation between C. indicum and C. funicola based on morphological characters of ascomatal hairs and species-specific protein expression patterns demonstrates that ascomatal hairs can be still used as potential morphological parameters in taxonomy of Chaetomium.

Three new azaphilones, chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3), and two new chlorinated phenolic glycosides, globosumoside A (4) and globosumoside B (5), were isolated from the crude extract of the fungal strain Chaetomium elatum No. 89-1-3-1. Their structures were determined by detailed NMR and MS spectroscopic analyses. The absolute configurations of C-7 in chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3) were assigned by CD experiments, and the absolute configurations of 1 and 2 were established by X-ray crystallography. Compounds 1-3 are the first examples of 7R-configurated azaphilones with a chlorinated isochromen from Chaetomium spp. In addition, compounds 1-3 showed inhibitory activity in the cysteine aspartyl-specific protease-3 (caspase-3) enzymatic assay, with IC₅₀ values of 20.6, 10.9, and 7.9 µM, respectively., (Georg Thieme Verlag KG Stuttgart · New York.)

Rationale: Chaetoglobosins are a family of macrocyclic polyketide alkaloids. They possess many similar isomers and exhibit a wide range of biological activities. Thus, there is a need for reliable, fast, and low-cost analysis of this class of compounds., Methods: A series of seven chaetoglobosins from Chaetomium globosum, including two types of isomers, were investigated using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in both positive- and negative-ion mode. The identity of major product ions was supported by deuterium-labeling experiments., Results: In positive-ion mode, the product ion at m/z 130 is the characteristic ion of the indolyl group. A McLafferty rearrangement might play a significant role in the fragmentation of the macrocycle moiety for most chaetoglobosins and produces two series of characteristic product ions, accompanied by neutral losses. The characteristic product ion at m/z 309 in the MS/MS spectrum of chaetoglobosins E indicates the structure of the cyclic olefinic bond in ring B and can be used to distinguish it from the isomers, chaetoglobosins F(ex) , which has an exocyclic double bond on ring B. In negative-ion mode, the McLafferty rearrangement has an important role in the fragmentation pattern of the macrocycle. Some high-abundance radical ions were detected. The radical product ion at m/z 138 might differentiate chaetoglobosins F and penochalasin F, isomers which have very similar structures., Conclusions: In summary, complementary information obtained from fragmentation experiments of [M+H](+) and [M-H](-) precursor ions is especially valuable for rapid identification of chaetoglobosins. The high-abundance radical ions in negative-ion mode are also of scientific interest., (Copyright © 2012 John Wiley & Sons, Ltd.)

Cellulases can be engineered with enhanced properties for broad use in scientific and industrial applications. In this study, the wild-type cbh2 gene of the thermophilic fungus Chaetomium thermophilum encoding cellobiohydrolase II (CBHII) was mutagenized through in vitro directed evolution. The resulting Pichia pastoris yeast library was screened, and two transformants were selected for enhanced CBHII activities that were not attributed to increased gene copy numbers. The optimum fermentation times of the two mutant transformants were shortened to 4-5 days after methanol induction compared to 6 days for the wild-type. The optimum reaction temperature (60 °C) and pH level (5 or 6) of the mutant CBHII proteins, designated CBHIIX16 and CBHIIX305, were higher than those of wild-type CBHII (50 °C and pH 4). Kept at 80 °C for 1 h, CBHIIX16 and CBHIIX305 retained >50% of their activities, while the wild-type CBHII lost all activity. Sequence analysis of CBHIIX16 and CBHIIX305 revealed that they contained five and six mutated amino acids, respectively. Structural modeling confirmed the presence of carbohydrate binding type-1 and catalytic domains, where the hydrogen bond numbers between the 227th and 203rd amino acids were increased, which perhaps contributed to the elevated enzyme stability. Therefore, the two CBHII mutants selected for increased enzymatic activities also demonstrated elevated optimum reaction temperature and pH levels and enhanced thermal stability. These properties may be beneficial in practical applications for CBHII.

Three new metabolites, chaetomugilin S, dechloro-chaetomugilin A and dechloro-chaetomugilin D, were isolated from a strain of Chaetomium globosum originally obtained from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated based on the basis of spectroscopic analyses, including 1D and 2D NMR techniques and some chemical transformations. Particularly, chaetomugilins T and U are the first compounds without a chlorine atom in azaphilones isolated from this fungal strain, to date. In addition, these compounds moderately inhibited the growth of cultured P388, HL-60, L1210 and KB cell lines.

One new cytochalasan alkaloid, chaetoglobosin V(b) (1), together with two structurally related known compounds, chaetoglobosin V (2) and chaetoglobosin G (3), was isolated from the ethyl acetate extract of a culture of the endophytic fungus Chaetomium globosum, associated with the leaves of Ginkgo biloba tree. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR and mass spectrometry. The absolute configuration of chaetoglobosin V(b) (1) was established by means of electronic circular dichroism (CD) spectroscopy, on the basis of the comparison between the CD spectrum of (+)-1 with that calculated with time-dependent density functional theory method for a simplified model. The correlation between compounds 1-3 was demonstrated by a biomimetic transformation of chaetoglobosin G (3) under mild conditions in chaetoglobosins V and V(b) (1 and 2). The isolated metabolites were tested against some phytopathogens., (Copyright © 2012 Wiley Periodicals, Inc.)

An endophytic fungus, strain L18, isolated from the medicinal plant Curcuma wenyujin Y.H. Chen et C. Ling was identified as Chaetomium globosum Kunze based on morphological characteristics and sequence data for the internal transcribed spacer (ITS-5.8S-ITS2) of the nuclear ribosomal DNA. A new metabolite named chaetoglobosin X (1), together with three known compounds erogosterol (2), ergosterol 5α,8-peroside (3) and 2-methyl-3-hydroxy indole (4), were isolated from C. globosum L18. Their structures were elucidated by spectroscopic methods including NMR, UV, IR and MS data and comparison with published data. Chaetoglobosin X (1) is hitherto unknown, whereas 2-methyl-3-hydroxy indole (4) is reported for the first time as a fungal metabolite, and erogosterol (2) and ergosterol 5α,8-peroside (3) are known fungal metabolites previously identified in other genera. Chaetoglobosin X (1) exhibited a broader antifungal spectrum and showed the strongest cytotoxic activity against H22 and MFC cancer cell lines., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The genus Chaetomium fungi are considered to be a rich source of novel and bioactive secondary metabolites of great importance. Up till now, a variety of more than 200 secondary metabolites belonging to diverse structural types of chaetoglobosins, epipolythiodioxopiperazines, azaphilones, xanthones, anthraquinones, chromones, depsidones, terpenoids, and steroids have been discovered. Most of these fungal metabolites exhibited antitumor, cytotoxic, antimalarial, enzyme inhibitory, antibiotic, and other activities. This review covers the extraction, structure elucidation, structural diversity, and biological activities of natural products isolated from about 30 fungi associated with marine- and terrestrial- origins, and highlights some bioactive compounds as well as their mechanisms of action and structure-activity relationships.

Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8-dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7-hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and 8, flavanone 7-O-β-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7-O-β-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195) also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'-trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7-O-α-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19). The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3, 16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A metabolite of 1, flavanone 7-O-β-D-O-glucopyranoside (22) was produced by Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. Metabolites 4 and 16 showed weak antileishmanial activity.

Four new azaphilones named longirostrerones A-D (1-4) and three known sterols, ergosteryl palmitate, ergosterol, and ergosterol peroxide, have been isolated from ethyl acetate extract of the fungus Chaetomium longirostre. These structures were determined by 1D and 2D NMR, IR, UV, MS, and CD spectroscopy. Compounds 1-4 exhibited strong cytotoxicity against KB cancer cell lines (IC(50) 0.23-6.38 μM), while only 1 showed potent cytotoxicity against MCF7 and NCI-H187 cell lines (IC50 0.24 and 3.08 μM, respectively). In addition, 1-3 showed antimalarial activity against Plasmodium falciparum (IC50 0.62-3.73 μM).

Four new metabolites, chaetomugilins P-R and 11-epi-chaetomugilin I, were isolated from a strain of Chaetomium globosum originally obtained 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 various chemical transformations. Particularly, the skeleton of chaetomugilin P is different from that of other azaphilones isolated from this fungal strain to date. In addition, these compounds significantly inhibited the growth of cultured P388, HL-60, L1210 and KB cell lines., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Six new azaphilones, 5'-epichaetoviridin A (7), 4'-epichaetoviridin F (9), 12β-hydroxychaetoviridin C (10), and chaetoviridins G-I (11-13), and six known azaphilones, chaetoviridins A-E (1-5) and 4'-epichaetoviridin A (8), were isolated from the endophytic fungus Chaetomium globosum cultivated in PDB medium for 21 days. The structure elucidation and the assignment of the relative configurations of the new natural products were based on detailed NMR and MS spectroscopic analyses. The structure of compound 1 was confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of compounds 4, 7, 8, and 12 were determined using Mosher's method. The antibiotic activity of the compounds was evaluated using an in vivo Caenorhabditis elegans infection model.

Precursor-fed cultivation of endophytic Chaetomium globosum 1C51 afforded nine novel "unnatural" halogenated chaetoglobosins including those with more preferable immunosuppressive activity.

Chaetoglocins A-D (1- 4), four new secondary metabolites, were isolated from the solid-fermentation culture of Chaetomium globosum (strain no. IFB-E036), an endophytic fungus residing inside the root of Cynodon dactylon. The structures of these compounds were elucidated on the basis of detailed spectroscopic evidence and by comparing spectroscopic data with those in the literature. Compounds 1 and 2 displayed antimicrobial activity against the gram-positive bacteria with minimum inhibitory concentrations (MIC) between 8 and 32 µg/mL., (© Georg Thieme Verlag KG Stuttgart · New York.)

Two new alkaloids chaetoglobosins V (1) and W (2), together with the six known congeners 3-8, were isolated through bioassay-guided fractionations from the EtOAc extract of a solid culture of Chaetomium globosum IFB-E041. The structures were elucidated by spectroscopic methods including mainly 1D and 2D NMR techniques. Chaetoglobosin W (2) was unique in its possession of an oxolane ring formed via an oxygen bridge between C-3 and C-6. The isolated fungal metabolites exhibited moderate cytotoxic activities against four human cancer cell lines (KB, K562, MCF-7, and HepG2) with their IC(50) values in a range of 18-30 µg/mL., (© Georg Thieme Verlag KG Stuttgart · New York.)

Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two new natural products, prochaetoglobosin III (2) and prochaetoglobosin III(ed) (3); six known chaetoglobosins B-D (4-6), F (7), and G (8) and isochaetoglobosin D (9) in addition to two known sterols, 24(R)-5alpha,8alpha-epidioxyergosta-6-22-diene-3beta-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium elatum ChE01. The structures of these compounds were elucidated by spectroscopic methods. Compounds 1-9 showed cytotoxicity against the human breast cancer (IC(50) 2.54-21.29 microM) and cholangiocarcinoma cell lines (IC(50) 3.41-86.95 microM).

Cytoglobosins A-G (1-7), seven new cytochalasan derivatives, along with two structurally related known compounds, isochaetoglobosin D (8) and chaetoglobosin F(ex) (9), were isolated and identified from the cultures of Chaetomium globosum QEN-14, an endophytic fungus derived from the marine green alga Ulva pertusa. The structures of the new natural products as well as their relative configurations were elucidated on the basis of 1D and 2D NMR spectra (COSY, HSQC, HMBC, and NOESY) and HRESIMS data. Cytoglobosins C and D (3 and 4) displayed cytotoxic activity against the A-549 tumor cell line.

A novel polyhydroxylated C(29)-sterol, 25xi-methyl-22-homo-5alpha-cholest-7,22-diene-3beta,6beta,9alpha-triol, designated globosterol (1), together with one known tetrahydroxylated ergosterol (22E, 24R)-ergosta-7,22-diene-3beta,5alpha,6beta,9alpha-tetraol (2) has been isolated from the cultures of an endophytic fungus, Chaetomium globosum ZY-22 originated from the plant Ginkgo biloba. The structures and relative configurations of 1 and 2 were established on the basis of extensive spectroscopic analyses including 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY) experiments and comparison with the literature. Globosterol (1) possesses an unprecedented 25-methyl Delta(22)-C(10)-side chain and Delta(7)-3beta,6beta,9alpha-hydroxy-steroid nucleus, which represents the first example for C(29)-steroids of the group.

Four new depsidones, mollicellins K-N (1-4), and six known depsidones, mollicellins B (5), C (6), E (7), F (8), H (9), and J (10), along with two known sterols were isolated from the fungus Chaetomium brasiliense. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic data and chemical transformation. Among these isolates, 1-3, 5-7, and 10 exhibited antimalarial activity against Plasmodium falciparum. Only 1 exhibited antimycobacterial activity against Mycobacterium tuberculosis and antifungal activity against Candida albicans using in vitro assays. In addition, 1-10 showed cytotoxicity against the KB, BC1, NCI-H187, and five cholangiocarcinoma cell lines.

Seco-chaetomugilins A and D 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, along with the chemical transformation from known chaetomugilins A and D. Seco-chaetomugilin D exhibited growth inhibitory activity against cultured P388, HL-60, L1210, and KB cells.

A hitherto unidentified endophytic strain of the genus Chaetomium, isolated from the medicinal plant Otanthus maritimus, yielded a new tetrahydrofuran derivative, aureonitolic acid (1), along with 5 known natural products, 2-6. The structure of 1 was determined by extensive spectroscopic analysis and comparison with reported data. Extracts of the fungus, grown either in liquid culture or on solid rice media, exhibited considerable cytotoxic activity when tested in vitro against L5178Y mouse lymphoma cells. Compounds 2 and 6 showed significant growth inhibition against L5178Y cells with EC50 values of 7.0 and 2.7 microg/mL, respectively, whereas 1 was inactive.

Fungal polyketides with the resorcylic acid lactone (RAL) scaffold are of interest for growth stimulation, the treatment of cancer, and neurodegenerative diseases. The RAL radicicol is a nanomolar inhibitor of the chaperone Hsp90, whose repression leads to a combinatorial blockade of cancer-causing pathways. Clustered genes for radicicol biosynthesis were identified and functionally characterized from the endophytic fungus Chaetomium chiversii, and compared to recently described RAL biosynthetic gene clusters. Radicicol production is abolished upon targeted inactivation of a putative cluster-specific regulator, or either of the two polyketide synthases that are predicted to collectively synthesize the radicicol polyketide core. Genomic evidence supports the existence of flavin-dependent halogenases in fungi: inactivation of such a putative halogenase from the C. chiversii radicicol locus yields dechloro-radicicol (monocillin I). Inactivation of a cytochrome P450 epoxidase furnishes pochonin D, a deepoxy-dihydro radicicol analog.

Chaetoglobins A (1) and B (2), two azaphilone alkaloid dimers with an unprecedented skeleton, were characterized from an endophytic fungus Chaetomium globosum with the former ascertained to be a significant cytotoxin valuable for anti-tumor drug discovery.

An endophytic fungus Chaetomium fusiforme was obtained from a liverwort, Scapania verrucosa. A comparison of the constituents of the ether extracts between S. verrucosa and the C. fusiforme culture was investigated by gas chromatography-mass spectrometry (GC/MS). The yield of ether extract based on dried plant material was 0.6% and 59 compounds were found in S. verrucosa. (+)-Aromadendrene (9.12%), hexadecanoic acid (6.92%), 6-isopropenyl-4,8a-dimethyl-1,2,3,5,6,7,8,8a-octahydro-naphthalen-2-ol (5.97%), s-tetrachloroethane (5.61%) and acetic acid (5.30%) were found to be the most abundant components among the 49 characterized compounds in S. verrucosa, which represented 84.64% of the total extract. However, the constituents of the cultured endophyte extract contained mainly acetic acid (35.05%), valeric acid, 3-methyl-, methyl ester (21.25%), and butane-2, 3-diol (12.24%). Although the extracts of S. verrucosa and its endophyte showed little chemical composition correlation, both of them demonstrated antifungal and antitumor activities. Furthermore, C. fusiforme has displayed a wider range of antimicrobial and antitumor activities, which were better than the host plant. These results could support the suggestion of endophytes as an alternative of the host for medicinal activity.

Chitinases play a major role in the defensive strategies of plants against fungal pathogens. In the current study, the gene for a 46-kDa endochitinase (chi46) was cloned from Chaetomium globosum, an important biocontrol fungus. The corresponding complementary deoxyribonucleic acid sequence was 1,350 bp in length, encoding 449 amino acid residues. The temporal expression of chi46, in response to the treatments of cell walls of six pathogens and confrontation against two fungal pathogens, was measured in C. globosum using real-time reverse transcription polymerase chain reaction. The expression of chi46 can be highly induced by exposure to the cell walls of plant pathogens and living pathogens, suggesting a role in plant disease resistance. The chi46 gene was inserted into the pPIC9 vector and transferred into the cells of Pichia pastoris GS115 for heterologous expression. The optimal reaction conditions for chitinase CHI46 activity were: 45 degrees C, pH of 5.0, and 5 mmol l(-1) of Cu2+. The maximum enzyme activity was 1.42 U ml(-1) following exposure to the cell wall chitin of Septoria tritici. The CHI46 enzyme can efficiently degrade cell walls of the phytopathogenic Rhizoctonia solani, Fusarium oxysporum, Sclerotinia sclerotiorum, Valsa sordida, S. tritici, and Phytophthora sojae, demonstrating that it may be involved in the biocontrol mechanism of C. globosum.

Chaetomium globosum is commonly found in water-damaged buildings and produces the mycotoxins chaetoglobosin A and chaetoglobosin C (Ch-A and Ch-C, respectively). While attempting to purify Ch-A and Ch-C, we observed that these mycotoxins were broken down after heating. The objective of this study was to determine the temperature and the amount of time necessary to break down Ch-A and Ch-C. We demonstrated that the amounts of Ch-A were significantly reduced when exposed to 75 degrees C for 24 h and 100 degrees C for 90, 120, or 150 min. Under the same conditions, the levels of Ch-C were also lower (although not significantly). At 175 degrees C, no Ch-A was detected after 15 min and Ch-C was significantly reduced after 30 min. Our findings will aid other researchers who work with these mycotoxins in the future.

A series of epipolythiodioxopiperazines in the fungus Chaetomium cochliodes was investigated using reversed-phase liquid chromatography with diode array detection and electrospray quadrupole time-of-flight-type tandem mass spectrometry in the positive ion mode. The fragmentation of protonated molecular ions including low-abundance parent ions, [M+H]+ for five known epipolythiodioxopiperazines, dethiotetra(methylthio)chetomin, chaetocochins A-C, and chetomin, was carried out using low-energy collision-induced electrospray ionization tandem spectrometry. It was found that McLafferty rearrangements occurred in the CID processes and produced a complementary pair of characteristic fragment ions containing piperazine rings (fused and unfused), especially to determine the number of S atoms on each ring. The fragmentation differential between [M+H]+ and [M+Na]+ was uncovered. Complementary fragmentation information obtained from [M+H]+ and [M+Na]+ precursor ions is especially valuable for rapid identification of epipolythiodioxopiperazines. A likely known compound, possibly related to chetoseminudin A, and three new species of epipolythiodioxopiperazines from the fungus C. cochliodes were identified or tentatively characterized based on tandem mass spectra of known ones.

Low-energy collision-induced electrospray ionization tandem mass spectrometry ESI-CID-MS/MS (in the positive ion mode) was used for the structural characterization of a series of five representative epioplythiodioxopipreazines: dethiotetra(methylthio)chemotin, chaetocochins A, B and C, and chemotin isolated from the fungus Chaetomium cochliodes. The fragmentation pathways were elucidated by ESI-IT-MS(n). The elemental compositions of most of the product ions were confirmed by low-energy ESI-CID-QTOF-MS/MS analyses. The loss of the S(2) molecule seems always to be the first when the S--S bond is present. The loss of 77 Da corresponding to the loss of the [CH(3)SCH(2)O]' radical was diagnostic for chaetocochins A and B, in which the two piperazines rings are linked by an acetal group. It was found that a McLafferty rearrangement plays a significant role in the skeleton fragmentation of theses series of studied complex multicyclic piperazine compounds. This MacLafferty rearrangement affords the product ions at m/z 416 and 400, containing the two piperazine rings belonging to the epipolythiodioxopipreazines. In addition, the pentacyclic rearrangement involving the loss of the SMe(.) radical seems to occur in the presence of the unfused ring. Finally the product ions at m/z 635 and 591 seem to be the characteristic ions for chaetocochin A.

Chaetominine (1), an alkaloidal metabolite with a new framework, was characterized from the solid-substrate culture of Chaetomium sp. IFB-E015, an endophytic fungus on the apparently healthy Adenophora axilliflora leaves. Its structure was determined by a combination of its spectral data and single-crystal X-ray diffraction analysis, with its absolute configuration elucidated by Marfey's method. Chaetominine was more cytotoxic than 5-fluorouracil against the human leukemia K562 and colon cancer SW1116 cell lines. [structure: see text]

Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xanthones, globosuxanthone C (3) and D (4), 2-hydroxyvertixanthone (5), and two known anthraquinones (6 and 7). The structures of the new compounds 1-4 were elucidated by NMR and MS techniques, and the relative stereochemistry of 1 was determined by X-ray crystallographic analysis. Of the compounds encountered, 1 was found to exhibit strong cytotoxicity against a panel of seven human solid tumor cell lines, disrupt the cell cycle leading to the accumulation of cells in either G2/M or S phase, and induce classic signs of apoptosis.

Cultivation of the endophytic fungus Chaetomium globosum, which was isolated from the inner tissue of the marine red alga Polysiphonia urceolata, resulted in the isolation of chaetopyranin (1), a new benzaldehyde secondary metabolite. Ten known compounds were also isolated, including two benzaldehyde congeners, 2-(2',3-epoxy-1',3'-heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl)benzaldehyde (2) and isotetrahydroauroglaucin (3), two anthraquinone derivatives, erythroglaucin (4) and parietin (5), five asperentin derivatives including asperentin (6, also known as cladosporin), 5'-hydroxy-asperentin-8-methylether (7), asperentin-8-methyl ether (8), 4'-hydroxyasperentin (9), and 5'-hydroxyasperentin (10), and the prenylated diketopiperazine congener neoechinulin A (11). The structures of these compounds were determined on the basis of their spectroscopic data analysis (1H, 13C, 1H-1H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution mass experiments). To our knowledge, compound 1 represents the first example of a 2H-benzopyran derivative of marine algal-derived fungi as well as of the fungal genus Chaetomium. Each isolate was tested for its DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging property. Compounds 1-4 were found to have moderate activity. Chaetopyranin (1) also exhibited moderate to weak cytotoxic activity toward several tumor cell lines.

Three new epipolythiodioxopiperazines, chaetocochins A (1), B (2), and C (3), along with dethio-tetra (methylthio) chetomin (4) and chetomin (5), were isolated from the ethyl acetate extract of the solid-state fermented rice culture of the fungus Chaetomium cochliodes. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1, 3, and 4 exhibited significant cytotoxicity in vitro against cancer cell lines Bre-04, Lu-04, and N-04.

[structure: see text] Chaetoindicins A-C (1-3), three isoquinolines with novel skeletons, were isolated from the solid-state fermented culture of Chaetomiumindicum. Their structures were elucidated on the basis of spectral data. X-ray crystallographic analysis confirmed the structure of 2.

Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the fungal fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC(50) = 79 nM in the CCR-5 receptor in vitro binding assay.

Three new azaphilones named rotiorinols A-C (1-3), two new stereoisomers, (-)-rotiorin (4) and epi-isochromophilone II (5), and a known compound, rubrorotiorin (6), were isolated from the fungus Chaetomium cupreum CC3003. Structures were established on the basis of spectroscopic evidence. The absolute configuration of 1 was determined by the modified Mosher's method along with an X-ray analysis of its acetate derivative, as well as by chemical transformation. Compounds 1, 3, 4, and 6 exhibited antifungal activity against Candida albicans with IC50 values of 10.5, 16.7, 24.3, and 0.6 microg/mL, respectively.

A new cytotoxic cytochalasan-based alkaloid named chaetoglobosin U (1), along with four known analogues, chaetoglobosins C (2), F (3), and E (5) and penochalasin A (4), has been characterized from the EtOAc extract of a solid culture of Chaetomium globosum IFB-E019, an endophytic fungus residing inside the stem of healthy Imperata cylindrica. The structure of chaetoglobosin U was determined through correlative analyses of its UV, IR, CD, MS, and 1D ((1)H and(13)C NMR and DEPT) and 2D NMR (COSY, NOESY, HMQC, and HMBC) data. Chaetoglobosin U (1) exhibited cytotoxic activity against the human nasopharyngeal epidermoid tumor KB cell line with an IC(50) value of 16.0 microM, comparable to that (14.0 microM) of 5-fluorouracil co-assayed as a positive reference. The known analogues 2-5 were moderately active to the cell line, with IC(50) values of 34.0, 52.0, 48.0, and 40.0 microM, respectively.

The Chaetomium globosum strain F0142, which was isolated from barnyard grass, showed potent disease control efficacy against rice blast (Magnaporthe grisea) and wheat leaf rust (Puccinia recondita). Two antifungal substances were purified from broth from this organism and identified as chaetoviridins A and B. Chaetoviridin A exhibited higher antifungal activity than chaetoviridin B against plant pathogenic fungi both in vitro and in vivo. Treatment with chaetoviridin A at 62.5 microg/mL suppressed the development of rice blast and wheat leaf rust by over 80%. The molecule also exhibited moderate control of tomato late blight, resulting in 50% control following the application of 125 microg/mL chaetoviridin A.

We discovered FR207944 produced by Chaetomium sp. No. 217 in the course of screening for antifungal antibiotics from natural products. FR207944 is identical with fuscoatroside, described in the preceding paper as an anti-Aspergillus flavus agent. Determination of the relative stereochemistry of fuscoatroside was made formally by comparison with WF11605 (16-Oxo-FR207944). We confirmed the stereochemistry on the basis of single crystal X-ray analysis.

Three new esters of orsellinic acid, globosumones A-C (1-3), and three known compounds, orsellinic acid (4), orcinol, and trichodion (5), were isolated from Chaetomium globosum endophytic on Ephedrafasciculata (Mormon tea). The structures of the new compounds 1-3 were established spectroscopically, which included 2D NMR experiments and 1H NMR studies on Mosher's ester derivatives. All compounds were evaluated for inhibition of cell proliferation in a panel of four cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), SF-268 (CNS glioma), and MIA Pa Ca-2 (pancreatic carcinoma), and normal human fibroblast cells (WI-38). Only globosumones A (1) and B (2) were found to be moderately active.

Unlabelled: Adsorption of microbial volatile organic compounds (MVOCs) on house dust was analyzed by performing solid phase microextraction (SPME) in combination with gas chromatography-mass spectrometry (GC-MS). Settled dust samples were exposed to five selected MVOCs and to cultures of the molds Stachybotrus chartarum, Aspergillus versicolor, and Chaetomium globosum. Considerable desorption of the MVOCs adsorbed on the dust occurred spontaneously within a few hours at room temperature and within several days or weeks after storage at -20 degrees or -80 degrees C. Similar results were found for a sample of a gypsum board cultivated with A. versicolor. SPME/GC-MS analysis performed immediately after sampling revealed several of the studied MVOCs on gypsum board and settled dust collected in a house garage with visible mold growth. MVOCs adsorbed on respirable particles of house dust can be inhaled and reach deep into the respiratory system, which may partly explain health effects that have been found to be associated with the presence of low concentrations of MVOCs in air. Particle-bound MVOCs can easily be detected by SPME/GC-MS analysis, thus this technique may prove to be very useful in indoor air research for identifying factors that affect human health., Practical Implications: We used SPME combined with GC-MS to study the adsorption and desorption of MVOCs on house dust particles that had been exposed to cultivated molds and molds in a damp building. Adsorbed MVOCs desorb spontaneously but this process can be slowed down by storing samples at -20 degrees or -80 degrees C. This opens up a possibility to apply SPME/GC-MS to reveal mold growth in buildings and to determine MVOCs in respirable dust particles that may reach deep in the respiratory system and lead to respiratory illnesses.

Nine cytotoxic metabolites, including three novel compounds, chaetoglobosins Q (1), R (2), and T (3), have been isolated from cultures of the fungus Chaetomium globosum. The structures were elucidated primarily from NMR spectroscopic data.

A screening study focusing on immunomodulatory activity of the EtOAc extract of an Ascomycete, Chaetomium seminudum, has afforded a known epipolythiodioxopiperazine, chetomin (1), together with three new chetomin-related metabolites named chetoseminudins A (2), B (3), and C (4). Among these four metabolites, 1 and 2 have been deduced as the immunosuppressive features of this fungus.

Gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) was applied to identify microbial volatile organic compounds (MVOCs) in water-damaged, mold-infested building materials (gypsum board papers (n=2), mineral wool, and masonite) and in cultivated molds (Aspergillus penicillioides, Stachybotrys chartarum, and Chaetomium globosum). Three SPME fibers (65-microm PDMS-DVB, 75-microm Carboxen-PDMS, and 70-microm Carbowax-stableflex) designed for automated injection were used of which the latter showed best performance. A number of previously reported MVOCs were detected both in the building materials and the cultivated molds. In addition, methyl benzoate was identified both in the S. chartarum and A. penicillioides cultures and in the building materials. SPME combined with GC-MS may be a useful method for the determination of MVOCs emitted from mold-infested building materials.