Structural Insights into Microbial One-Carbon Metabolic Enzymes Ni-Fe-S-Dependent Carbon Monoxide Dehydrogenases and Acetyl-CoA Synthases

Ni-Fe-S-dependent carbon monoxide dehydro-genases (CODHs) are enzymes that interconvert CO and CO2 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 CO2 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 CO2-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 CO2, methanogens use A- and C-clusters of an acetyl-CoA decarbonylase/synthase complex (ACDS) to break down acetate en route to CO2 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.

Automated summary

Ni-Fe-S-dependent carbon monoxide dehydrogenases play important roles in the microbiota of animals, facilitating the use of CO and CO2 as carbon sources and maintaining redox homeostasis. CODH/ACS is responsible for acetate production, while ACDS is involved in acetate breakdown.