Identification of the First Diphenyl Ether Gene Cluster for Pestheic Acid Biosynthesis in Plant Endophyte Pestalotiopsis fici |
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Authors: | Xinxin Xu Dr. Ling Liu Dr. Fan Zhang Dr. Wenzhao Wang Jinyang Li Prof. Liangdong Guo Prof. Yongsheng Che Prof. Gang Liu |
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Affiliation: | 1. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101 (China);2. Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Haidian District, Beijing 100850 (China) |
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Abstract: | The diphenyl ether pestheic acid was isolated from the endophytic fungus Pestalotiopsis fici, which is proposed to be the biosynthetic precursor of the unique chloropupukeananes. The pestheic acid biosynthetic gene (pta) cluster was identified in the fungus through genome scanning. Sequence analysis revealed that this gene cluster encodes a nonreducing polyketide synthase, a number of modification enzymes, and three regulators. Gene disruption and intermediate analysis demonstrated that the biosynthesis proceeded through formation of the polyketide backbone, cyclization of a polyketo acid to a benzophenone, chlorination, and formation of the diphenyl ether skeleton through oxidation and hydrolyzation. A dihydrogeodin oxidase gene, ptaE, was essential for diphenyl ether formation, and ptaM encoded a flavin‐dependent halogenase catalyzing chlorination in the biosynthesis. Identification of the pta cluster laid the foundation to decipher the genetic and biochemical mechanisms involved in the pathway. |
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Keywords: | flavin‐dependent halogenases natural products oxidative coupling reaction Pestalotiopsis fici pestheic acid biosynthesis |
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