Repurposing metalloproteins as mimics of natural metalloenzymes for small-molecule activation.

Artificial metalloenzymes (ArMs) consist of an unnatural metal or cofactor embedded in a protein scaffold, and are an excellent platform for applying the concepts of protein engineering to catalysis. In this Focused Review, we describe the application of ArMs as simple, tunable artificial models of the active sites of complex natural metalloenzymes for small-molecule activation. In this sense, ArMs expand the strategies of synthetic model chemistry to protein-based supporting ligands with potential for participation from the second coordination sphere. We focus specifically on ArMs that are structural, spectroscopic, and functional models of enzymes for activation of small molecules like CO, CO2, O2, N2, and NO, as well as production/consumption of H2. These ArMs give insight into the identities and roles of metalloenzyme structural features within and near the cofactor. We give examples of ArM work relevant to hydrogenases, acetyl-coenzyme A synthase, superoxide dismutase, heme oxygenases, nitric oxide reductase, methyl-coenzyme M reductase, copper-O2 enzymes, and nitrogenases.