Channeling of carbon monoxide during anaerobic carbon dioxide fixation

Carbon monoxide is an intermediate in carbon dioxide fixation by diverse mi crobes that inhabit anaerobic environments including the human colon. These organisms fix CO2 by the Wood-Ljungdahl pathway of acetyl-CoA biosynthesis . The bifunctional CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) catalyze s several key steps in this pathway. CO2 is reduced to CO at a nickel iron- sulfur cluster called cluster C located in the CODH subunit. Then, CO is co ndensed with a methyl group and coenzyme A at cluster A, another nickel iro n-sulfur cluster in the ACS subunit. Spectroscopic studies indicate that cl usters A and C are at least 10-15 Angstrom apart. To gain a better understa nding of how CO production and utilization are-coordinated, we have studied an isotopic exchange reaction between labeled CO2 and the carbonyl group o f acetyl-CoA with the CODH/ACS from Clostridium thermoaceticum. When soluti on CO is provided at saturating levels, only CO2-derived CO is incorporated into the carbonyl group of acetyl-CoA. Furthermore, when high levels of he moglobin or myoglobin are added to remove CO from solution, there is only p artial inhibition of the incorporation of CO2-derived CO into acetyl-CoA. T hese results provide strong evidence for the existence of a CO channel betw een cluster C in the CODH subunit and cluster A in the ACS subunit. The exi stence of such a channel would tightly couple CO production and utilization and help explain why high levels of this toxic gas do nor escape into the environment. Instead, microbes sequester this energy-rich carbon source for metabolic reactions.