A Bacterial Cytochrome P450 Enzyme Catalyzes Multistep Oxidation Reactions in Pyrroindomycin Biosynthesis
作者机构：Department of ChemistryShanghai Normal University100 Guiling RoadShanghai200233 China State Key Laboratory of Bioorganic and Natural Products ChemistryCenter for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of Sciences345 Lingling RoadShanghai200032 China Department of General DentistryShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of Stomatology639 Zhizaoju RoadShanghai200011 China
出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)
年 卷 期：2023年第41卷第19期
页 面：2439-2445页
核心收录：
学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学]
基 金：supported in part by grants from the National Key Research and Development Program of China(2022YFC2303100) the National Natural Science Foundation of China(22193070,32030002,81974495 and 21977109) the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZLCX20212401)
主 题：Cytochrome P450 enzyme Pyrroindomycin Multistep oxidation reactions Enzyme catalysis Selectivity
摘 要：Cytochrome P450 enzymes (P450s) belong to a large family of oxidative hemeproteins and catalyze highly diverse oxygenation reactions that are involved in the biosynthesis of various natural products. Here, we report a multifunctional cytochrome P450 enzyme, PyrE2, which catalyzes the regioselective, successive 6-electron oxidation of an inert methyl group to produce a carboxyl product through formation of the hydroxyl and aldehyde intermediates in pyrroindomycin biosynthesis. The time-course biotransformation was characterized by the presence of the hydroxyl and aldehyde intermediates, the lag of the formation of the carboxyl product, and the subsequent loss of both intermediates, indicating that each 2-electron oxidation exhibits the distributive mechanism that requires substrate binding and product releasing. Bioinformatics analysis shows that the homologs of pyrE2 are common in the gene clusters of the spirotetronates varying in the oxidative state of the corresponding exocyclic carbon, indicating the generality and diversity of P450-catalyzed oxygenation in related biosynthetic pathways.
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