Abstract
Ni-Fe-S-dependent carbon monoxide dehydrogenases (CODHs) are enzymes that interconvert CO and CO(2) by using their catalytic Ni-Fe-S C-cluster and their Fe-S B- and D-clusters for electron transfer. CODHs are important in the microbiota of animals such as humans, ruminants, and termites because they can facilitate the use of CO and CO(2) as carbon sources and serve to maintain redox homeostasis. The bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is responsible for acetate production via the Wood-Ljungdahl pathway, where acetyl-CoA is assembled from two CO(2)-derived one-carbon units. A Ni-Fe-S A-cluster is key to this chemistry. Whereas acetogens use the A- and C-clusters of CODH/ACS to produce acetate from CO(2), methanogens use A- and C-clusters of an acetyl-CoA decarbonylase/synthase complex (ACDS) to break down acetate en route to CO(2) and methane production. Here we review some of the recent advances in understanding the structure and mechanism of CODHs, CODH/ACSs, and ACDSs, their unusual metallocofactors, and their unique metabolic roles in the human gut and elsewhere.