期刊
JOURNAL OF NATURAL PRODUCTS
卷 81, 期 4, 页码 1060-1064出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.7b00835
关键词
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资金
- National Natural Science Foundation of China [31500033, 31670098, 31670097]
- Natural Science Foundation of Jiangsu Province [BK20150388]
- National Key R&D Program of China [2017YFD0201405]
- Major Basic Program of the Natural Science Foundation of Shandong Province, China [ZR2017ZB0212]
- Shandong Provincial Natural Science Foundation, China [ZR2017BC059]
- China Postdoctoral Science Foundation [2017M612261]
- Recruitment Program of Global Experts
- Qilu Youth Scholar Startup Funding of SDU
The indole alkaloid antibiotic chuangxinmycin, from Actinobacteria Actinoplanes tsinanensis, containing a unique thiopyrano[4,3,2-cd]indole scaffold, is a potent and selective inhibitor of bacterial tryptophanyl-tRNA synthetase. The chuangxinmycin biosynthetic gene cluster was identified by in silico analysis of the genome sequence, then verified by heterologous expression. Systemic gene inactivation and intermediate identification determined the minimum set of genes for unique thiopyrano[4,3,2-cd]indole formation and the concerted action of a radical S-adenosylmethionine protein plus an unknown protein for addition of the 3-methyl group. These findings set a solid foundation for comprehensively investigating the biosynthesis, optimizing yield, and generating new analogues of chuangxinmycin.
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