A new gliotoxin analogue from a marine-derived fungus<i>Aspergillus fumigatus</i>Fres

Wen, Zhao; Zhu, Tian Jiao; Han, Xiao; Fan, Guo Tao; Liu, Hong Bing; Zhu, Wei; Gu, Qian Qun

doi:10.1080/14786410600906970

Cited by 25 publications

(13 citation statements)

References 11 publications

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“…These analyses confirmed the presence of the gliotoxins 1–3 and 8 , as well as their dehydroderivatives 5–7 and 9 . 15c, 16 We further identified cyclo(L-Phe-L-Ser) ( 10 ), 17 not previously reported from A. fumigatus extracts nor other gliotoxin-producing fungi, as well as bis - N -norgliovictin ( 11 ), a known A. fumigatus metabolite 18 not previously associated with the gli cluster.…”

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confidence: 63%

Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis

et al. 2011

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Gliotoxin (1), a major product of the gli non-ribosomal peptide synthetase (NRPS) gene cluster, is strongly associated with virulence of the opportunistic human pathogen Aspergillus fumigatus. Despite identification of the gli cluster, the pathway of gliotoxin biosynthesis has remained elusive, in part because few potential intermediates have been identified. In addition, previous studies suggest that knowledge of gli-dependent metabolites is incomplete. Here we use differential analysis by 2D NMR spectroscopy (DANS) of metabolite extracts derived from gli knock-out and wild-type (WT) strains to obtain a detailed inventory of gli-dependent metabolites. DANS-based comparison of the WT metabolome with that of ΔgliZ, a knock-out strain devoid of the gene encoding the transcriptional regulator of the gli cluster, revealed nine novel gliZ-dependent metabolites including unexpected structural motifs. Their identification provides insight into gliotoxin biosynthesis and may benefit studies of the role of the gli cluster in A. fumigatus virulence. Our study demonstrates the utility of DANS for correlating gene expression and metabolite biosynthesis in microorganisms.

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confidence: 63%

Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis

et al. 2011

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“…Compounds 10 – 13 were identified as 6-acetylbis(methylthio)gliotoxin ( 10 ) [28], bisdethiobis(methylthio)gliotoxin ( 11 ) [29], didehydrobisdethiobis(methylthio)gliotoxin ( 12 ) [30] and bis- N -norgliovictin ( 13 ) [31], respectively, by comparing their spectroscopic data (Table 4 and Supplementary Figures S53–S60) with the literature values. In the literature, only the 1 H NMR data of compound 12 were reported; here, we report the detailed 1 H and 13 C NMR data.…”

Section: Resultsmentioning

confidence: 99%

Exploring the Chemodiversity and Biological Activities of the Secondary Metabolites from the Marine Fungus Neosartorya pseudofischeri

Liang

et al. 2014

Marine Drugs

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The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2,3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylene-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 2–14 and the cytotoxic activity of compounds 4, 5 and 7–13 were evaluated. Their structure-activity relationships are also preliminarily discussed.

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“…On the other hand, the difficulties of retrieving a "sustained, reliable" harvest of a marine organism, insufficient quantities of material to allow for study completion, and difficulties culturing marine organism in the lab were the main reasons for the lack of development in the area of marine pharmaceuticals (Bhadury et al 2006). As interests have turned to marine microorganisms, the fungi have begun to be recognized as a likely source of potentially useful natural products (Bhadury et al 2006;Abdel-Lateff et al 2009;Chen et al 2009;D'Souza-Ticlo et al 2009;Du et al 2009;Kathiresan et al 2009;Sun et al 2009;Tsukamoto et al 2009;Trisuwan et al 2009;Zhao et al 2009). In fact, fungi from the marine environment have shown great potential by the diversity of secondary metabolites (Bugni and Ireland 2004).…”

Section: Comparison Of Culturable Fungal Diversity Of the Two Marine mentioning

confidence: 97%

Phylogenetic diversity of culturable fungi associated with two marine sponges: Haliclona simulans and Gelliodes carnosa, collected from the Hainan Island coastal waters of the South China Sea

Liu

Zhu

et al. 2010

Fungal Diversity

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The diversity and biological activities of fungi associated with the two sponges, Haliclona simulans and Gelliodes carnosa, were investigated using a culturedependent method followed by analysis of the fungal rDNA-ITS sequences. The two sponges were collected from the coastal waters of Lingshui Bay of Hainan Island in the South China Sea. A total of 37 independent fungal isolates corresponding to 30 different species were obtained from the two sponges. Nearly two thirds of the strains (n=24, 64.9%) had close affiliations (identity (ID) or similarity≥98%) with their best matches in GenBank. Another one third of the isolates (n=13, 35.1%) were distantly related to their closest relatives (ID<98%), implying that these species are possibly different from those previously reported. The two sponges possessed similar fungal diversities. Haliclona simulans harbored a mainly different fungal consortium as compared with that of the same sponge species collected from Irish coastal waters, suggesting that the fungal diversity associated with the sponges is more dependent on the surrounding environment than on the sponge species. Biological activities of the fungal culture extracts were tested against the human tumor cell lines, mainly, a human lung carcinoma cell line (A-549), a human liver carcinoma cell line (Bel-7402), and a human colon carcinoma cell line (HCT-8), and against the Gram positive bacterium Bacillus subtilis. A relatively high proportion of positive results were obtained in this study, demonstrating that fungi isolated from sponges could be a rich source of new biologically active natural products.

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A new gliotoxin analogue from a marine-derived fungusAspergillus fumigatusFres

Cited by 25 publications

References 11 publications

Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis

Identification of Cryptic Products of the Gliotoxin Gene Cluster Using NMR-Based Comparative Metabolomics and a Model for Gliotoxin Biosynthesis

Exploring the Chemodiversity and Biological Activities of the Secondary Metabolites from the Marine Fungus Neosartorya pseudofischeri

Phylogenetic diversity of culturable fungi associated with two marine sponges: Haliclona simulans and Gelliodes carnosa, collected from the Hainan Island coastal waters of the South China Sea

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