聚酮
化学
立体化学
芳构化
生物合成
羟醛反应
单加氧酶
内酯
生物化学
吡喃酮
酶
细胞色素P450
催化作用
作者
Fang Wen Jiao,Yi Shuang Wang,Xue You,Wanqing Wei,Yu Chen,Cheng Yang,Zhi Kai Guo,Bo Zhang,Yong Liang,Ren Xiang Tan,Rui Jiao,Hui Ming Ge
标识
DOI:10.1002/anie.202112047
摘要
Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13 C-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 α-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 γ-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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