Bioinformatic Discovery of a Cambialistic Monooxygenase

Dinuclear monooxygenases mediate challenging C-H bond oxidation reactions throughout Nature. Many of these enzymes are presumed to exclusively utilize diiron cofactors. Herein, we report the bioinformatic discovery of an orphan dinuclear monooxygenase that preferentially utilizes a heterobimetallic manganese-iron (Mn/Fe) cofactor to mediate an O2 dependent C-H bond hydroxylation reaction. Unlike the structurally similar Mn/Fe-dependent monooxygenase AibH2, the diiron form of this enzyme (SfbO) exhibits nascent enzymatic activity. This behavior raises the possibility that many other dinuclear monooxygenases may be endowed with the capacity to harness cofactors with variable metal content.