Riboflavin Is Directly Involved in N-Dealkylation Catalyzed by Bacterial Cytochrome P450 Monooxygenases
Riboflavin Is Directly Involved in N-Dealkylation Catalyzed by Bacterial Cytochrome P450 Monooxygenases
复制标题
核黄素直接参与细菌细胞色素 P450 单加氧酶催化的 N-脱烷基化
DOI：
10.1002/cbic.202000071
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发表时间：
2020
期刊：
影响因子：
3.2
通讯作者：
Chen Yijun
中科院分区：
文献类型：
--
作者：
Zhang Chengchang;Lu Meiling;Lin Lin;Huang Zhangjian;Zhang Rongguang;Wu Xuri;Chen Yijun
与自然界中大量的酶一样，细菌细胞色素P450单加氧酶需要活化形式的黄素作为催化活性的辅因子。核黄素是FAD和FMN的前体，是黄素酶不可或缺的辅因子。与先前的概念相反，在本文中，我们描述了通过细菌P450单加氧酶直接由核黄素介导的N-脱烷基化的电子转移过程的鉴定。基于X射线晶体学、分子模拟和分子动力学模拟、定点突变和代表性细菌P450单加氧酶的生化分析相结合，提出了从NADPH到核黄素，然后通过活性氧到血红素的电子传递。这项研究为细菌P450酶催化中的电子转移机制提供了新的见解，并可能在酵母，真菌，植物和哺乳动物中。
Like a vast number of enzymes in nature, bacterial cytochrome P450 monooxygenases require an activated form of flavin as a cofactor for catalytic activity. Riboflavin is the precursor of FAD and FMN that serves as indispensable cofactor for flavoenzymes. In contrast to previous notions, herein we describe the identification of an electron‐transfer process that is directly mediated by riboflavin for N‐dealkylation by bacterial P450 monooxygenases. The electron relay from NADPH to riboflavin and then via activated oxygen to heme was proposed based on a combination of X‐ray crystallography, molecular modeling and molecular dynamics simulation, site‐directed mutagenesis and biochemical analysis of representative bacterial P450 monooxygenases. This study provides new insights into the electron transfer mechanism in bacterial P450 enzyme catalysis and likely in yeasts, fungi, plants and mammals.