[MoCu]‐Dependent Carbon Monoxide Dehydrogenases

Abstract

Abstract [MoCu]‐dependent carbon monoxide dehydrogenases (Mo‐CODH) catalyze the hydroxylation of CO, which produces CO 2 and consumes H 2 O in the process. Aerobic carbon monoxide oxidizing bacteria and archaea use Mo‐CODH to generate energy by providing the respiratory chain with CO‐derived electrons, and aerobic CO‐oxidizers that possess the genes for CO 2 fixation can also use CO as a carbon source. Due to the pervasive nature of CO in the atmosphere as a trace gas, and the numerous marine and terrestrial environments enriched in CO due to its production during the decomposition of organic matter, aerobic CO‐oxidizers are widespread and significantly contribute to the biogeochemical cycle of CO. Mo‐CODH has been structurally characterized by both X‐ray crystallography and cryo‐EM. Structural and biochemical characterization of the purified Mo‐CODH enzyme has focused on bacteria that mediate carboxydotrophic growth such as Afipia carboxidovorans , which were isolated from environments with elevated concentrations of CO. Only recently has a Mo‐CODH enzyme capable of oxidizing CO to subatmospheric levels been isolated and characterized, from Mycobacterium smegmatis, providing the first insights into structural features that enable high‐affinity CO oxidation. In all aerobic CO oxidizers, CO oxidation occurs at a unique [MoSCu] dimetallic site within the active site of Mo‐CODH, through a mechanism that has been the subject of several computational and biochemical studies. Two [2Fe–2S] clusters facilitate the transport of electrons from the active site to a FAD cofactor, which then donates electrons to an electron carrier. Quinones are believed to be the primary physiological electron acceptor of Mo‐CODH, which can be transported from the cell membrane through the cytoplasm to the soluble Mo‐CODH complex by the CoxG shuttle protein.