title: Channeling of carbon monoxide during anaerobic carbon dioxide fixation.
abstract: Carbon monoxide is an intermediate in carbon dioxide fixation by diverse microbes that inhabit anaerobic environments including the human colon. These organisms fix CO(2) by the Wood-Ljungdahl pathway of acetyl-CoA biosynthesis. The bifunctional CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) catalyzes several key steps in this pathway. CO(2) is reduced to CO at a nickel iron-sulfur cluster called cluster C located in the CODH subunit. Then, CO is condensed with a methyl group and coenzyme A at cluster A, another nickel iron-sulfur cluster in the ACS subunit. Spectroscopic studies indicate that clusters A and C are at least 10-15 A apart. To gain a better understanding of how CO production and utilization are coordinated, we have studied an isotopic exchange reaction between labeled CO(2) and the carbonyl group of acetyl-CoA with the CODH/ACS from Clostridium thermoaceticum. When solution CO is provided at saturating levels, only CO(2)-derived CO is incorporated into the carbonyl group of acetyl-CoA. Furthermore, when high levels of hemoglobin or myoglobin are added to remove CO from solution, there is only partial inhibition of the incorporation of CO(2)-derived CO into acetyl-CoA. These results provide strong evidence for the existence of a CO channel between cluster C in the CODH subunit and cluster A in the ACS subunit. The existence of such a channel would tightly couple CO production and utilization and help explain why high levels of this toxic gas do not escape into the environment. Instead, microbes sequester this energy-rich carbon source for metabolic reactions.
authors.affiliation: Department of Biochemistry, Beadle Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0664, USA.
authors.forename: J
authors.initials: J
authors.lastname: Seravalli
authors.forename: S W
authors.initials: SW
authors.lastname: Ragsdale
mesh_terms: D000105:Acetyl Coenzyme A / Q000096:biosynthesis / Q000737:chemistry; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000693:Anaerobiosis; D002245:Carbon Dioxide / Q000737:chemistry* / Q000378:metabolism; D002248:Carbon Monoxide / Q000737:chemistry* / Q000378:metabolism; D003013:Clostridium / Q000201:enzymology; D006454:Hemoglobins / Q000737:chemistry; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D002248:Carbon Monoxide; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase