Metalloradical-driven enzymatic CO2 reduction by a dynamic Ni–Fe cluster

Abstract Carbon monoxide dehydrogenases (CODHs) selectively catalyse the reversible reduction of CO 2 to CO and water. The catalytic centre of CODHs contains a unique [NiFe 4 (OH)(µ 3 -S) 4 ] cluster whose role in activating and converting CO 2 is poorly understood. Here we reveal the structures of all catalytically relevant oxidation states with and without substrates and products bound. We show that the Ni–Fe cluster combines a rigid Fe–S core with a dynamic Ni(I/II)–Fe(II) dyad. The redox-active element is the Ni ion, cycling between square-planar Ni(II) and T-shaped Ni(I) states with metalloradical character, the latter serving as the nucleophile for CO 2 activation. The Fe(II) ion switches between two positions, the one preceding CO 2 activation is close to Ni(I) with a potential Ni(I)–Fe(II) interaction and the other binds the substrates CO 2 and water. We demonstrate how the Ni–Fe cluster creates an efficient CO 2 reduction catalyst and provides a blueprint for the design of novel catalysts based on abundant transition metals.