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Updated: Jun 10, 2025

Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
Mechanistic Perspective on Oxygen Activation Chemistry by Flavoenzymes
1State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering and Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen, 361005, P. R. China.
Abstract:
Flavin-dependent enzymes catalyze a panoply of chemical transformations essential for living organisms. Through oxygen activation, flavoenzymes could generate diverse flavin-oxygen species that mediate numerous redox and non-redox transformations. In this review, we highlight the extensive oxygen activation chemistry at two sites of the flavin cofactor: C4a and N5 sites. Oxygen activation at the C4a site generates flavin-C4aOO(H) species for various monooxygenation reactions, while activation at the N5 site produces negatively charged flavin-N5OOH species, which act as highly reactive nucleophiles or bases. The selective oxygen activation at either the C4a or N5 site depends on the nature of substrates and is controlled by the active site architecture. These insights have expanded our understanding of oxygen activation chemistry in flavoenzymes and will serve as a foundation for future efforts in enzyme engineering and redesign.
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