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- Title
An NADPH‐Dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis.
- Authors
Jiao, Fang Wen; Wang, Yi Shuang; You, Xue Ting; Wei, Wanqing; Chen, Yu; Yang, Cheng Long; Guo, Zhi Kai; Zhang, Bo; Liang, Yong; Tan, Ren Xiang; Jiao, Rui Hua; Ge, Hui Ming
- Abstract
Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13C‐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.
- Subjects
POLYKETIDES; BAEYER-Villiger rearrangement; BIOSYNTHESIS; CARBONYL group; MONOOXYGENASES; OXIDATION-reduction reaction; AROMATIZATION
- Publication
Angewandte Chemie, 2021, Vol 133, Issue 50, p26582
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202112047