硫醚
生物合成
硫黄
化学
硫化氢
基因簇
天然产物
生物化学
酶
基因
立体化学
生物
硫代谢
有机化学
作者
Mingming Cao,Cheng‐Jian Zheng,Dong Yang,Edward Kalkreuter,Ajeeth Adhikari,Yu‐Chen Liu,Mostafa E. Rateb,Ben Shen
标识
DOI:10.1002/anie.202015570
摘要
Abstract Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur‐containing angucyclines has been discovered, and yet, the sulfur incorporation step is poorly understood. In this work, a series of thioether‐bridged angucyclines were discovered, and a cryptic epoxide Michael acceptor intermediate was revealed en route to thioangucyclines (TACs) A and B. However, systematic gene deletion of the biosynthetic gene cluster (BGC) by CRISPR/Cas9 could not identify any gene responsible for the conversion of the epoxide intermediate to TACs. Instead, a series of in vitro and in vivo experiments conclusively showed that the conversion is the result of two non‐enzymatic steps, possibly mediated by endogenous hydrogen sulfide. Therefore, the TACs are proposed to derive from a detoxification process. These results are expected to contribute to the study of both angucyclines and the utilization of inorganic sulfur in natural product biosynthesis.
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