Cobalamin (vitamin B 12 )-dependent enzymes play pivotal roles in essential primary metabolism and diverse natural product biosynthetic pathways. Due to the unique reactivity of cobalt, the function of cobalamin cannot be readily replaced by other abundant transition metals. When embedded in the corrin ring of vitamin B 12 , the cobalt center exhibits distinctive redox properties, enabling biochemical transformations that involve either homolytic or heterolytic cleavage of coordinated axial ligands such as methyl and adenosyl groups. Recent studies have shown that vitamin B 12 -dependent enzymes can be repurposed to perform unnatural radical-mediated reactions. Furthermore, artificial cobalt-containing cofactors can be incorporated into non-native protein scaffolds, thereby enabling catalytic activities beyond those of natural B 12 -dependent enzymes. This review highlights the recent progress in the engineering of protein-based cobalt catalysts, with emphasis on the expanded catalytic repertoires enabled by the distinct chemical reactivity of the cobalt center.
Ueno et al. (Fri,) studied this question.