Epigenetic Genome Mining of an Endophytic Fungus Leads to the Pleiotropic Biosynthesis of Natural Products |
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| Authors: | Dr Xu‐Ming Mao Dr Wei Xu Dr Dehai Li Dr Wen‐Bing Yin Dr Yit‐Heng Chooi Dr Yong‐Quan Li Dr Yi Tang Dr Youcai Hu |
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| Affiliation: | 1. Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA);2. College of Life Sciences, Zhejiang University, Hangzhou 310058 (China);3. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 (China);4. Current address: State Key Laboratory of Mycology, The Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China);5. Current address: Research School of Biology, Australian National University, Canberra, ACT 0200 (Australia);6. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050 (China) |
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| 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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| Keywords: | biosynthesis endophytic fungi epigenetics gene expression natural products |
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