期刊
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
卷 104, 期 16, 页码 7131-7142出版社
SPRINGER
DOI: 10.1007/s00253-020-10765-y
关键词
FR901533; Endothelin-converting enzyme inhibitor; Polyketide biosynthesis; Streptosporangium roseum; Gene disruption
资金
- National Science Foundation Award [CHE-1429195]
FR901533 (1, also known as WS79089B), WS79089A (2), and WS79089C (3) are polycyclic aromatic natural products with promising inhibitory activity to endothelin-converting enzymes. In this work, we isolated five tridecaketide products fromStreptosporangium roseumNo. 79089, including1-3, benaphthamycin (4) and a novel FR901533 analogue (5). The structure of5was characterized based on spectroscopic data. Compared with the major product2, the new compound5has an additional hydroxyl group at C-12 and an extra methyl group at the 13-OH. The configuration of C-19 of these compounds was determined to beRusing Mosher's method. A putative biosynthetic gene cluster for compounds1-5was discovered by analyzing the genome ofS. roseumNo. 79089. This 38.6-kb gene cluster contains 38 open reading frames, including a minimal polyketide synthase (wsaA-C), an aromatase (wsaD), three cyclases (wsaE,F, andW), and a series of tailoring enzymes such as monooxygenases (wsaO1-O7) and methyltransferases (wsaM1andM2). Disruption of the ketosynthase gene (wsaA) in this gene cluster abolished the production of1-5, confirming that this gene cluster is indeed responsible for the biosynthesis of1-5. A type II polyketide biosynthetic pathway was proposed for this group of natural endothelin-converting enzyme inhibitors.
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