Snapshots of acetyl-CoA synthesis, the final step of CO₂fixation in the Wood-Ljungdahl pathway

Abstract

In the ancient microbial Wood-Ljungdahl pathway, CO2is 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 acetogenClostridium autoethanogenum, characterizing the molecular choreography of the overall reaction including electron transfer to the CODH for CO2reduction, 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 CO2fixation in anaerobic organisms.One-Sentence Summary:Structural description of key states of CO2fixation by the carbon monoxide dehydrogenase/acetyl-CoA synthase complex.