title: Epigenetic genome mining of an endophytic fungus leads to the pleiotropic biosynthesis of natural products.
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.
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).|College of Life Sciences, Zhejiang University, Hangzhou 310058 (China).
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Mao
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).|Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 (China).
authors.forename: Dehai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).|Current address: State Key Laboratory of Mycology, The Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China).
authors.forename: Wen-Bing
authors.initials: WB
authors.lastname: Yin
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA).|Current address: Research School of Biology, Australian National University, Canberra, ACT 0200 (Australia).
authors.forename: Yit-Heng
authors.initials: YH
authors.lastname: Chooi
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058 (China).
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA). yitang@ucla.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Chemical and Biomolecular Engineering and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (USA). huyoucai@imm.ac.cn.|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). huyoucai@imm.ac.cn.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Hu
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D057890:Epigenomics; D005658:Fungi / Q000378:metabolism*; D015870:Gene Expression; D023281:Genomics; D015394:Molecular Structure
chemical_list: D001688:Biological Products
keywords: biosynthesis; endophytic fungi; epigenetics; gene expression; natural products