Control of catalysis in flavin-dependent monooxygenases

Abstract

Flavoprotein monooxygenases reduce flavins, speed their reaction with oxygen, and stabilize a C4a-oxygen adduct long enough to use this reactive species to transfer an oxygen atom to a substrate. The flavin-oxygen adduct can be the C4a-peroxide anion, in which case it reacts as a nucleophile. The protonated adduct - the C4a-hydroperoxide - reacts as an electrophile. The elimination of H(2)O(2) competes with substrate oxygenation. This side-reaction is suppressed, preventing the waste of NAD(P)H and the production of toxic H(2)O(2). Several strategies have been uncovered that prevent the deleterious side-reaction while still allowing substrate hydroxylation.