Heterologous Expression Guides Identification of the Biosynthetic Gene Cluster of Chuangxinmycin, an Indole Alkaloid Antibiotic
Heterologous Expression Guides Identification of the Biosynthetic Gene Cluster of Chuangxinmycin, an Indole Alkaloid Antibiotic
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异源表达指导吲哚生物碱抗生素创新霉素生物合成基因簇的鉴定。
DOI:
10.1021/acs.jnatprod.7b00835
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发表时间:
2018-04-01
影响因子:
5.1
通讯作者:
Zhang, Youming
中科院分区:
文献类型:
--
作者:
Xu, Xiaokun;Zhou, Haibo;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.