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

Date

2015

Authors

Mao, Xu-Ming
Xu, Wei
Li, Dehai
Yin, Wen-Bing
Chooi, Yit-Heng
Li, Yong-Quan
Tang, Yi
Hu, Youcai

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Volume Title

Publisher

Wiley-VCH Verlag GMBH

Abstract

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.

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Citation

Source

Angewandte Chemie International Edition

Type

Journal article

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DOI

10.1002/anie.201502452

Restricted until

2037-12-31