TY - INPR A1 - Yin, Max Dongsheng A1 - Lemaire, Olivier N. A1 - Rosas-Jiménez, José Guadalupe A1 - Belhamri, Mélissa A1 - Shevchenko, Anna A1 - Hummer, Gerhard A1 - Wagner, Tristan A1 - Murphy, Bonnie J. T1 - Snapshots of acetyl-CoA synthesis, the final step of CO₂ fixation in the Wood-Ljungdahl pathway T2 - bioRxiv N2 - In the ancient microbial Wood-Ljungdahl pathway, CO2 is fixed in a multi-step process 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 CO2 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 CO2 fixation in anaerobic organisms. Y1 - 2024 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/86498 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-864981 UR - https://www.biorxiv.org/content/10.1101/2024.08.05.606187v1 IS - 2024.08.05.606187v1 PB - bioRxiv ER -