Enzymatic Hydroxylation of Aliphatic C-H Bonds by a Mn/Fe Cofactor

The aerobic oxidation of carbon-hydrogen (C-H)bondsin biology is currently known to be accomplished by a limited setof cofactors that typically include heme, nonheme iron, and copper.While manganese cofactors perform difficult oxidation reactions, includingwater oxidation within Photosystem II, they are generally not knownto be used for C-H bond activation, and those that do catalyzethis important reaction display limited intrinsic reactivity. Herewe report that the 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis, AibH1H2, requires manganeseto functionalize a strong, aliphatic C-H bond (BDE = 100 kcal/mol).Structural and spectroscopic studies of this enzyme reveal a redox-active,heterobimetallic manganese-iron active site at the locus of O-2 activation and substrate coordination. This resultexpands the known reactivity of biological manganese-iron cofactors,which was previously restricted to single-electron transfer or stoichiometricprotein oxidation. Furthermore, the AibH1H2 cofactor is supportedby a protein fold distinct from typical bimetallic oxygenases, andbioinformatic analyses identify related proteins abundant in microorganisms.This suggests that many uncharacterized monooxygenases may similarlyrequire manganese to perform oxidative biochemical tasks.

Automated summary

The 2-aminoisobutyric acid hydroxylase from Rhodococcus wratislaviensis requires manganese to functionize a strong, aliphatic C-H bond. Structural and spectroscopic studies reveal a redox-active, heterobimetallic manganese-iron active site at the locus of O-2 activation and substrate coordination. This expands the known reactivity of biological manganese-iron cofactors and suggests the involvement of manganese in oxidative biochemical tasks.