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Reductive Acetyl-CoA pathway
The reductive acetyl-coenzyme A (CoA) pathway, also known as the Wood-Ljungdahl pathway, was discovered by Harland G. Wood and Lars G. Ljungdahl in 1965, thanks to their studies on Clostridium thermoaceticum, a Gram positive bacterium now named Moorella thermoacetica. It is an acetogen, an anaerobic bacteria that uses CO2 as electron acceptor and carbon source, and H2 as an electron donor to form acetic acid. This metabolism is wide spread within the phylum Firmicutes, especially in the Clostridia.

The pathway is also used by methanogens, which are mainly Euryarchaeota, and several anaerobic chemolithoautotrophs, such as sulfate-reducing bacteria and archaea. It is probably performed also by the Brocadiales, an order of Planctomycetes that oxidize ammonia in anaerobic condition.

The Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase is the oxygen-sensitive enzyme that permits the reduction of CO2 to CO and the synthesis of acetyl-CoA in several reactions.

One branch of this pathway, the methyl branch, is similar but non homologous between bacteria and archaea. In this branch happens the reduction of CO2 to a methyl residue bound to a cofactor. The intermediates are formate for bacteria and formyl-methanofuran for archaea, and also the carriers, tetrahydrofolate and tetrahydropterins respectively in bacteria and archaea, are different, such as the enzymes forming the cofactor-bound methyl group.

Otherwise, the carbonyl branch is homologous between the two domains and consists of the reduction of another molecule of CO2 to a carbonyl residue bound to an enzyme, catalyzed by the CO dehydrogenase/acetyl-CoA synthase. This key enzyme is also the catalyst for the formation of acetyl-CoA starting from the products of the previous reactions, the methyl and the carbonyl residues.

This carbon fixation pathway requires only one molecule of ATP for the production of one molecule of pyruvate, which makes this process one of the main choice for chemolithoautotrophs limited in energy and living in anaerobic conditions.