Snapshots of acetyl-CoA synthesis, the final step of CO ₂ fixation in the Wood-Ljungdahl pathway

In the ancient microbial Wood-Ljungdahl pathway, CO ₂ is fixed in a multi-step process ending with acetyl-CoA synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). Here, we present catalytic snapshots of the CODH/ACS from the gas-converting acetogen Clostridium autoethanogenum , characterizing the molecular choreography of the overall reaction including electron transfer to the CODH for CO ₂ reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer and protect the reaction intermediates. Altogether, the structures allow us to draw a detailed reaction mechanism of this enzyme crucial for CO ₂ fixation in anaerobic organisms.

One-Sentence Summary: Structural description of key states of CO ₂ fixation by the carbon monoxide dehydrogenase/acetyl-CoA synthase complex.