In enzymology, carbon monoxide dehydrogenase (CODH) () is an enzyme that catalyzes the chemical reaction CO + H2O + A CO2 + AH2 The chemical process catalyzed by carbon monoxide dehydrogenase is similar to the water-gas shift reaction. The 3 substrates of this enzyme are CO, H2O, and A, whereas its two products are CO2 and AH2. A variety of electron donors/receivers (Shown as "A" and "AH2" in the reaction equation above) are observed in micro-organisms which utilize CODH. Several examples of electron transfer cofactors has been proposed, including Ferredoxin, NADP+/NADPH and flavoprotein complexes like flavin adenine dinucleotide (FAD) as well as hydrogenases. CODHs support the metabolisms of diverse prokaryotes, including methanogens, aerobic carboxidotrophs, acetogens, sulfate-reducers, and hydrogenogenic bacteria. The bidirectional reaction catalyzed by CODH plays a role in the carbon cycle allowing organisms to both make use of CO as a source of energy and utilize CO2 as a source of carbon. CODH can form a monofunctional enzyme, as is the case in Rhodospirillum rubrum, or can form a cluster with acetyl-CoA synthase as has been shown in M.thermoacetica. When acting in concert, either as structurally independent enzymes or in a bifunctional CODH/ACS unit, the two catalytic sites are key to carbon fixation in the reductive acetyl-CoA pathway Microbial organisms (Both aerobic and anaerobic) encode and synthesize CODH for the purpose of carbon fixation (CO oxidation and CO2 reduction). Depending on attached accessory proteins (A,B,C,D-Clusters), serve a variety of catalytic functions, including reduction of [4Fe-4S] clusters and insertion of nickel. This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with other acceptors. The systematic name of this enzyme class is carbon-monoxide:acceptor oxidoreductase. Other names in common use include anaerobic carbon monoxide dehydrogenase, carbon monoxide oxygenase, carbon-monoxide dehydrogenase, and carbon-monoxide:(acceptor) oxidoreductase.

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