Reconstruction of Cladoniamide Biosynthesis Reveals Nonenzymatic Routes to Bisindole Diversity

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• 作者：Yi-Ling Du ; David E. Williams ; Brian O. Patrick ; Raymond J. Andersen ; Katherine S. Ryan
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：December 19, 2014
• 年：2014
• 卷：9
• 期：12
• 页码：2748-2754
• 全文大小：783K
• ISSN：1554-8937

文摘

Indolotryptolines are bisindole natural products isolated from microbial and eDNA sources. Here, we report the sequence of transformations that convert an indolocarbazole to the indolotryptoline cladoniamide through reconstruction of the four-enzyme cascade in E. coli. This cascade involves, first, conversion of an indolocarbozole to a C4c-C7a cis diol by ClaX1; second, N-methylation by ClaM1; third, rearrangement to the indolotryptoline scaffold by ClaX2; and fourth, installation of an O-methyl group by ClaM3. We furthermore elucidate the origins of minor cladoniamides D鈥揋 as the products of nonenzymatic, base-catalyzed opening of the succinimide ring of cladonimiades A鈥揃. Overall, this work reveals the precarious pathway indolocarbazole-derived metabolites must traverse as they are converted into indolotryptoline products and highlights the importance of nonenzymatic chemistry in generating bisindole diversity.