A Bacterial Cytochrome P450 Enzyme Catalyzes Multistep Oxidation Reactions in Pyrroindomycin Biosynthesis
A Bacterial Cytochrome P450 Enzyme Catalyzes Multistep Oxidation Reactions in Pyrroindomycin Biosynthesis
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DOI：
10.1002/cjoc.202300178
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发表时间：
2023-06-24
影响因子：
5.4
通讯作者：
Liu, Wen
中科院分区：
文献类型：
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作者：
Wang, Jiabao;Xu, Yu;Liu, Wen
细胞色素 P450 酶 (P450) 属于氧化血红素蛋白大家族，可催化参与各种天然产物生物合成的高度多样化的氧化反应。在这里，我们报道了一种多功能细胞色素P450酶PyrE2，它催化惰性甲基的区域选择性连续6电子氧化，通过在吡咯吲哚霉素生物合成中形成羟基和醛中间体来产生羧基产物。时程生物转化的特征是羟基和醛中间体的存在、羧基产物形成的滞后以及随后两种中间体的损失，表明每个2电子氧化表现出需要底物结合和产物释放的分配机制。生物信息学分析表明，pyrE2的同源物在相应环外碳的氧化状态不同的螺酮酯基因簇中很常见，表明相关生物合成途径中P450催化氧化的普遍性和多样性。
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.