Wood–Ljungdahl pathway

The Wood–Ljungdahl pathway is a set of biochemical reactions used by some bacteria and archaea called acetogens and methanogens, respectively. It is also known as the reductive acetyl-coenzyme A (Acetyl-CoApathway.[1] This pathway enables these organisms to use hydrogen as an electron donor, and carbon dioxide as an electron acceptor and as a building block for biosynthesis.

The reductive acetyl–CoA pathway

In this pathway carbon dioxide is reduced to carbon monoxide and formic acid or directly into a formyl group, the formyl group is reduced to a methyl group and then combined with the carbon monoxide and Coenzyme A to produce acetyl-CoA. Two specific enzymes participate on the carbon monoxide side of the pathway: CO Dehydrogenase and acetyl-CoA synthase. The former catalyzes the reduction of the CO2 and the latter combines the resulting CO with a methyl group to give acetyl-CoA.[1][2]

Some anaerobic bacteria and archaea use the Wood–Ljungdahl pathway in reverse to break down acetate. For example, some methanogens break down acetate to a methyl group and carbon monoxide, and then reduce the methyl group to methane while oxidizing the carbon monoxide to carbon dioxide.[3] Sulfate reducing bacteria, meanwhile, oxidize acetate completely to CO2 and H2 coupled with the reduction of sulfate to sulfide.[4] When operating in the reverse direction, the acetyl-CoA synthase is sometimes called acetyl-CoA decarbonylase.

The pathway occurs in both bacteria (e.g. acetogens) and archaea (e.g. methanogens[5]). Unlike the Reverse Krebs cycle and the Calvin cycle, this process is not cyclic. A recent study of the genomes of a set of bacteria and archaea suggests that the last universal common ancestor (LUCA) of all cells was using the Wood–Ljungdahl pathway in a hydrothermal setting.[6] Phylometabolic reconstructions also supports this.[7] However, recent experiments have tried to replicate this pathway by attempting to reduce CO2, with very little pyruvate observed using native iron as a reducing agent (<0.03 mM),[8] and even less so under hydrothermal settings with H2 (10 μM). 


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 Metasyntactic variable, which is released under the 
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