Structural highlights
FunctionPublication Abstract from PubMedMicrobial sulfur-containing secondary metabolites show various biological activities and the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp2)-H thiolation by the P450 in chuangxinmycin biosynthesis. The cytochrome P450 catalyzing C-S bond formation in S-heterocyclization of chuangxinmycin biosynthesis.,Shi Y, Jiang Z, Hu X, Hu X, Gu R, Jiang B, Zuo L, Li X, Sun H, Zhang C, Wang L, Wu L, Hong B Angew Chem Int Ed Engl. 2021 Apr 21. doi: 10.1002/anie.202015814. PMID:33884733[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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