Heterologous expression guides identification of the biosynthetic gene cluster of chuangxinmycin, an indole alkaloid antibiotic.

Authors: Xu, Xiaokun and Zhou, Haibo and Liu, Yang and Liu, Xiaotong and Fu, Jun and Li, Aiying and Li, Yue-Zhong and Shen, Yuemao and Bian, Xiaoying and Zhang, Youming

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.

Journal: Journal of natural products
DOI: 10.1021/acs.jnatprod.7b00835
Year: 2018

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