Cryptic Sulfur Incorporation in Thioangucycline Biosynthesis

被引：18

作者：

Cao, Mingming ^{[1
]}

Zheng, Chengjian ^{[1
]}

Yang, Dong ^{[1
]}

Kalkreuter, Edward ^{[1
]}

Adhikari, Ajeeth ^{[1
]}

Liu, Yu-Chen ^{[1
]}

Rateb, Mostafa E. ^{[1
]}

Shen, Ben ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, Dept Mol Med, Nat Prod Discovery Ctr Scripps Res, Jupiter, FL 33458 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2021年 / 60卷 / 13期

关键词：

angucycline; biosynthetic gene cluster; detoxification products; epoxide; sulfur incorporation; ANGUCYCLINE ANTIBIOTIC URDAMYCIN; HYDROGEN-SULFIDE; STREPTOMYCES; GENE; H2S; REDUCTION; MYCOTHIOL; RHODANESE; CYSTEINE; GENOME;

D O I：

10.1002/anie.202015570

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：7140 / 7147

页数：8

共 52 条

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