O2 Activation and Enzymatic C-H Bond Activation Mediated by a Dimanganese Cofactor

Dioxygen (O2) is a potent oxidant used by aerobic organisms for energy transduction and critical biosynthetic processes. Numerous metallocofactors, which most commonly feature iron or copper ions, harness O2 to mediate C-H bond hydroxylation reactions. In contrast, most manganese-dependent enzymes are redox-inert and infrequently activate O2 or C-H bonds. Here we report that the dimanganese-metalated form of the cambialistic monooxygenase SfbO (Mn2-SfbO) can efficiently mediate enzymatic C-H bond hydroxylation. Kinetic, spectroscopic and structural studies invoke a mixed-valent dimanganese cofactor (Mn2II/III) in catalytic O2 activation. Access to this redox form requires stoichiometric superoxide to mature a Mn2II cofactor to higher-valent forms that participate in catalysis. These findings establish the viability of proteinaceous dimanganese cofactors in mediating complex, multistep redox transformations.