Identifying the Minimal Enzymes for Unusual Carbon-Sulfur Bond Formation in Thienodolin Biosynthesis
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- 作者：Yaya Wang ; Jiali Wang ; Shuqi Yu ; Fan Wang ; Dr. Hongmin Ma ; Dr. Changwu Yue ; Minghao Liu ; Prof. Dr. Zixin Deng ; Prof. Dr. Ying Huang and Prof. Dr. Xudong Qu
- 关键词：biosynthesis ; carbon-sulfur bond ; indole-S-hetero scaffold ; natural products ; thienodolin ; tryptophan amino transferase
- 刊名：ChemBioChem
- 出版年：2016
- 出版时间：May 3, 2016
- 年：2016
- 卷：17
- 期：9
- 页码：799-803
- 全文大小：646K
- ISSN：1439-7633
文摘
Thienodolin (THN) features a tricyclic indole-S-hetero scaffold that encompasses two unique carbon–sulfur bonds. Although its biosynthetic gene cluster has been recently identified in Streptomyces albogriseolus, the essential enzymes for the formation of C−S bonds have been relatively unexplored. Here, we isolated and characterized a new biosynthetic gene cluster from Streptomyces sp. FXJ1.172. Heterologous expression, systematic gene inactivation, and in vitro biochemical characterization enable us to determine the minimum set of genes for THN synthesis, and an aminotransferase (ThnJ) for catalyzing the downstream conversion of tryptophan chlorination. In addition, we evaluated (and mainly excluded) a previously assumed pivotal intermediate by feeding experiments. With these results, we narrowed down four enzymes (ThnC–F) that are responsible for the two unprecedented C−S bond formations. Our study provides a solid basis for further unraveling of the unique C−S mechanisms.