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Riboflavin Is Directly Involved in N‐Dealkylation Catalyzed by Bacterial Cytochrome P450 Monooxygenases
Author(s) -
Zhang Chengchang,
Lu Meiling,
Lin Lin,
Huang Zhangjian,
Zhang Rongguang,
Wu Xuri,
Chen Yijun
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000071
Subject(s) - monooxygenase , flavin group , cofactor , cytochrome p450 , riboflavin , chemistry , enzyme , flavoprotein , biochemistry , cytochrome , mutagenesis , oxygenase , heme , hemeprotein , stereochemistry , mutant , gene
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.