Dataset Information

Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp.

ABSTRACT: The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) was used to turn on the biosynthesis of EGM-556, a new cyclodepsipeptide of hybrid biosynthetic origin, isolated from the Floridian marine sediment-derived fungus Microascus sp. The absolute configurations of three chiral centers were determined by Marfey's derivatization. EGM-556 represents one of the few examples in which silent biosynthetic genes, encoding a new secondary metabolite, were activated by means of epigenetic manipulation of the fungal metabolome.

SUBMITTER: Vervoort HC

PROVIDER: S-EPMC3031758 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp.

Vervoort Hélène C HC Drašković Marija M Crews Phillip P

Organic letters 20101221 3

The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) was used to turn on the biosynthesis of EGM-556, a new cyclodepsipeptide of hybrid biosynthetic origin, isolated from the Floridian marine sediment-derived fungus Microascus sp. The absolute configurations of three chiral centers were determined by Marfey's derivatization. EGM-556 represents one of the few examples in which silent biosynthetic genes, encoding a new secondary metabolite, were activated by means of epi ...[more]

PMID: 21174394

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Project description:Microorganisms produce a wide range of natural products (NPs) with clinically and agriculturally relevant biological activities. In bacteria and fungi, genes encoding successive steps in a biosynthetic pathway tend to be clustered on the chromosome as biosynthetic gene clusters (BGCs). Historically, "activity-guided" approaches to NP discovery have focused on bioactivity screening of NPs produced by culturable microbes. In contrast, recent "genome mining" approaches first identify candidate BGCs, express these biosynthetic genes using synthetic biology methods, and finally test for the production of NPs. Fungal genome mining efforts and the exploration of novel sequence and NP space are limited, however, by the lack of a comprehensive catalog of BGCs encoding experimentally-validated products. In this study, we generated a comprehensive reference set of fungal NPs whose biosynthetic gene clusters are described in the published literature. To generate this dataset, we first identified NCBI records that included both a peer-reviewed article and an associated nucleotide record. We filtered these records by text and homology criteria to identify putative NP-related articles and BGCs. Next, we manually curated the resulting articles, chemical structures, and protein sequences. The resulting catalog contains 197 unique NP compounds covering several major classes of fungal NPs, including polyketides, non-ribosomal peptides, terpenoids, and alkaloids. The distribution of articles published per compound shows a bias toward the study of certain popular compounds, such as the aflatoxins. Phylogenetic analysis of biosynthetic genes suggests that much chemical and enzymatic diversity remains to be discovered in fungi. Our catalog was incorporated into the recently launched Minimum Information about Biosynthetic Gene cluster (MIBiG) repository to create the largest known set of fungal BGCs and associated NPs, a resource that we anticipate will guide future genome mining and synthetic biology efforts toward discovering novel fungal enzymes and metabolites.

Dataset Information

Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp.

Publications

Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp.

Similar Datasets

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