Wood-Ljungdahl (reductive acetyl-CoA) pathway

The reductive acetyl-CoA pathway, by which acetogenic bacteria and methanogenic and acetoclastic archaea fix two molecules of CO2 into the two carbons of acetyl-CoA. It is the only carbon-fixation route that is linear rather than cyclic, and the only one that conserves energy as it fixes carbon. Two branches converge on one active site: the methyl branch reduces CO2 to formate and carries it through tetrahydrofolate-bound C1 intermediates down to a methyl group, which is handed to a corrinoid iron-sulfur protein; the carbonyl branch reduces a second CO2 to enzyme-bound carbon monoxide. Acetyl-CoA synthase then condenses the methyl group, the carbonyl and coenzyme A. The pathway runs on low-potential ferredoxin, is irreversibly oxygen-sensitive at the nickel-iron-sulfur A-cluster, and is widely held to be among the most ancient metabolisms. It is a sibling of the other non-Calvin fixation routes (MODULE:reductive_tca_cycle, MODULE:hydroxypropionate_bicycle) and of MODULE:calvin_benson_bassham_cycle; unlike those, it references none of them, because its product is acetyl-CoA directly.

Grounded on the acetogen Moorella thermoacetica (reclassified Neomoorella thermoacetica, which is why the reviewed entries carry both names), whose core proteins are all in Swiss-Prot. Archaea run the same chemistry on tetrahydromethanopterin rather than tetrahydrofolate and assemble the activities into the ACDS/CODH complex (GO:0044672); that complex term is deliberately NOT asserted here, because it names the archaeal acetyl-CoA-decarbonylase/synthase complex and this module's exemplars are the bacterial CODH/ACS. A realization in an archaeon should assert it. The methylenetetrahydrofolate reductase step carries no representative member: no reviewed M. thermoacetica entry exists for it, and the unreviewed candidates could not be confidently assigned, so the descriptor stands without one rather than naming a guess. The formate dehydrogenase shown is the NADP-dependent, selenium- and tungsten-containing enzyme of this organism; other acetogens use hydrogen-dependent CO2 reductase instead, which is a realization difference at the same step. Energy conservation by the Rnf or Ech complexes and by flavin-based electron bifurcation is what makes the pathway exergonic overall, but it is a separate bioenergetic module and is named rather than modelled. The direction matters: these enzymes also run oxidatively in acetoclastic and syntrophic metabolism, which is the same module traversed backwards, not a different one. The CODH/ACS subunits are named here as UniProt names them, by EC number and by alpha/beta: the literature's AcsA (CODH) and AcsB (ACS) do not map onto UniProt's alpha and beta in the order one would guess, and UniProt asserts no gene name for either entry, so none is asserted here. The unambiguous anchors are the EC numbers: P27989 carries EC 1.2.7.4 (CO dehydrogenase) and P27988 carries EC 2.3.1.169 (acetyl-CoA synthase).