Epigenetic Genome Mining of an Endophytic Fungus Leads to Pleiotropic Biosynthesis of Natural Products

Details

• Alternative Title:
  Angew Chem Int Ed Engl
• Personal Author:
  Mao, Xu-Ming ; Xu, Wei ; Li, Dehai ; Yin, Wen-Bing ; Chooi, Yit-Heng ; Li, Yong-Quan ; Tang, Yi ; Hu, Youcai
• Description:
  The small-molecule biosynthetic potential of most filamentous fungi has remained largely unexplored and represents an attractive source for the discovery of new compounds. Genome sequencing of Calcarisporium arbuscula, a mushroom-endophytic fungus, revealed 68 core genes that are involved in natural product biosynthesis. This is in sharp contrast to the predominant production of the ATPase inhibitors aurovertin B and D in the wild-type fungus. Inactivation of a histone H3 deacetylase led to pleiotropic activation and overexpression of more than 75 % of the biosynthetic genes. Sampling of the overproduced compounds led to the isolation of ten compounds of which four contained new structures, including the cyclic peptides arbumycin and arbumelin, the diterpenoid arbuscullic acid A, and the meroterpenoid arbuscullic acid B. Such epigenetic modifications therefore provide a rapid and global approach to mine the chemical diversity of endophytic fungi.
• Subjects:
  Article Biological Products Endophytic Fungus Epigenetic Regulation Epigenomics Fungi Gene Expression Genome Mining Genomics Molecular Structure Natural Products

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• Source:
  Angew Chem Int Ed Engl. 54(26):7592-7596
• Pubmed ID:
  26013262
• Pubmed Central ID:
  PMC4487767
• Document Type:
  Journal Article
• Funding:
  DP1 GM106413/GM/NIGMS NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/
• Volume:
  54
• Issue:
  26
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:14900b964c9cdd9ecdc113891a7d3e3ed6cd23b16f17b6fac33b34061c4a786d
• Download URL:
  https://stacks.cdc.gov/view/cdc/32930/cdc_32930_DS1.pdf
• File Type:
  [PDF - 1.28 MB ]