Cytochrome P450 Monooxygenase for Catalyzing C-42 Hydroxylation of the Glycine-Derived Fragment in Hangtaimycin Biosynthesis

• DOI: 10.1021/acs.orglett.2c00242
• Publication Date: 2022-02-09T13:47:51Z
• Authors: Xingxing Li; Jie Fu; Yihua Li; Jiachang Liu; Rongmei Gao; Yuanyuan Shi; Yihong Li; Hongmin Sun; Lifei Wang; Yuhuan Li; Bingya Jiang; Linzhuan Wu; Bin Hong
• Keywords: Hydroxylation; Gene cluster

A hybrid trans-AT PKS/NRPS gene cluster htm was identified with defined boundaries for hangtaimycin biosynthesis in Streptomyces spectabilis CPCC200148. Deoxyhangtaimycin, a new derivative of hangtaimycin, from the htm11 knockout mutant. In vitro biochemical assays demonstrated that cytochrome P450 monooxygenase Htm11 responsible stereoselective hydroxylation deoxyhangtaimycin to hangtaimycin. More importantly, showed activity against influenza virus at micromolar level, highlighting its potential as an antiviral lead compound.