Recent advances in tuning redox properties of electron transfer centers in metalloenzymes catalyzing oxygen reduction reaction and H2 oxidation important for fuel cells design.

Current fuel-cell catalysts for oxygen reduction reaction (ORR) and H2 oxidation use precious metals and, for ORR, require high overpotentials. In contrast, metalloenzymes perform their respective reaction at low overpotentials using earth-abundant metals, making metalloenzymes ideal candidates for inspiring electrocatalytic design. Critical to the success of these enzymes are redox-active metal centers surrounding the enzyme active sites that ensure fast electron transfer (ET) to or away from the active site, by tuning the catalytic potential of the reaction as observed in multicopper oxidases but also in dictating the catalytic bias of the reaction as realized in hydrogenases. This review summarizes recent advances in studying these ET centers in multicopper oxidases and heme-copper oxidases that perform ORR and hydrogenases in carrying out H2 oxidation. Insights gained from understanding how the reduction potential of the ET centers effects reactivity at the active site in both the enzymes and their models are provided.