title: Evidence that carbon monoxide is an obligatory intermediate in anaerobic acetyl-CoA synthesis.
abstract: Carbon monoxide is produced by several biological reactions. It is proposed to act as an intracellular signaling molecule and can serve as the carbon and electon source for certain bacteria. Direct evidence for a new biological role for CO is presented here. The results strongly indicate that CO is produced as an obligatory intermediate during growth of the acetogenic bacterium Clostridium thermoaceticum on glucose, H2/CO2, or aromatic carboxylic acids. Our results are consistent with earlier hypotheses of the intermediacy of CO during growth of acetogenic bacteria on CO2 and hexoses [Diekert, G., & Ritter, M. (1983) FEMS Microbiol. Lett. 17, 299-302] and methanogenic Archaea on CO2 [Stupperich, E., Hammel, K. E., Fuchs, G., & Thauer, R. K. (1983) FEBS Lett. 152, 21-23]. Therefore, CO production is a key step in the Wood-Ljungdahl pathway of acetyl-CoA synthesis. The carbonyl group of acetyl-CoA is shown to be formed from the carboxyl group of pyruvate by the following steps. (i) Pyruvate undergoes decarboxylation by pyruvate:ferredoxin oxidoreductase to form acetyl-CoA and CO2. (ii) CO2 is reduced to CO by the CODH site of the bifunctional enzyme CO dehydrogenase/acetyl-CoA synthase (CODH/ACS). (iii) CO generated in situ combines with the ACS active site to form a paramagnetic adduct that has been called the NiFeC species, and (iv) the bound carbonyl group combines with a bound methyl group and CoA to generate acetyl-CoA. To our knowledge, this paper represents the first demonstration of a pathway in which CO is produced and then used as a metabolic intermediate.
authors.affiliation: Department of Biochemistry, University of Nebraska, Lincoln 68588-0664, USA.
authors.forename: S
authors.initials: S
authors.lastname: Menon
authors.forename: S W
authors.initials: SW
authors.lastname: Ragsdale
mesh_terms: D000106:Acetate-CoA Ligase / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000096:biosynthesis / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000693:Anaerobiosis; D002245:Carbon Dioxide / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D003013:Clostridium / Q000254:growth & development / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism; D050743:Pyruvate Synthase; D011773:Pyruvates / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006601:Hexoses; D009097:Multienzyme Complexes; D011773:Pyruvates; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D002248:Carbon Monoxide; D000445:Aldehyde Oxidoreductases; D007658:Ketone Oxidoreductases; D050743:Pyruvate Synthase; C019823:carbon monoxide dehydrogenase; D000106:Acetate-CoA Ligase