Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is a bi-functional enzyme of particular interest for enzymatic energy conversion, due to its ability to convert CO<sub>2 </sub>to acetyl quickly, selectively, and at the thermodynamic redox equilibrium, outperforming all proposed synthetic mimics. In the CODH/ACS complex, there are two types of active cluster, connected by a network of tunnels and alcoves which transport substrates internally. In this study we focus on the A-cluster, a four-iron, four-sulfur cluster bridged to a di-nickel motif, located in the ACS sub-units, which is responsible for converting CO to acetyl. An exact mechanistic understanding of the processes occurring at the A-cluster has remained elusive. Using density functional theory calculations on extended cluster models, and quantum mechanics/molecular mechanics (QM/MM) methods to address the role of the extended protein environment, we investigated the electronic and structural features of the A-cluster and its ligands. A particular emphasis was placed on understanding the oxidation states that the cluster cycles through, and their associated redox potentials. Additionally, our analysis considered the interaction of bound ligands with the cluster in different states.

Insights into the mechanism of the A-cluster in the CODH/ACS enzyme from first principles calculations

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.