An NADPH-Dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis

文献类型： 外文期刊

第一作者： Jiao, Fang Wen

作者： Jiao, Fang Wen;Wang, Yi Shuang;You, Xue Ting;Yang, Cheng Long;Zhang, Bo;Tan, Ren Xiang;Jiao, Rui Hua;Ge, Hui Ming;Wang, Yi Shuang;Tan, Ren Xiang;Wei, Wanqing;Chen, Yu;Liang, Yong;Guo, Zhi Kai

作者机构：

关键词： Baeyer-Villiger monooxidase; biosynthesis; chartreusin; ketoreductase; skeletal rearrangement

期刊名称：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION （ 影响因子：15.336； 五年影响因子：14.205 ）

ISSN： 1433-7851

年卷期： 2021 年 60 卷 50 期

页码：

收录情况： SCI

摘要： Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early C-13-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the alpha-pyrone containing pentacyclic intermediate in an NADPH-dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous gamma-lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide.

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