Conformational dynamics of a multienzyme complex in anaerobic carbon fixation

• Published in: Science (American Association for the Advancement of Science) Vol. 387; no. 6733; pp. 498 - 504
• Main Authors: Yin, Max Dongsheng, Lemaire, Olivier N., Rosas Jiménez, José Guadalupe, Belhamri, Mélissa, Shevchenko, Anna, Hummer, Gerhard, Wagner, Tristan, Murphy, Bonnie J.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 31.01.2025; American Association for the Advancement of Science (AAAS)
• Subjects: Acetate-CoA Ligase - chemistry; Acetate-CoA Ligase - metabolism; Acetyl Coenzyme A - biosynthesis; Aldehyde Oxidoreductases - chemistry; Aldehyde Oxidoreductases - metabolism; Anaerobic microorganisms; Anaerobic processes; Anaerobiosis; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Carbon Cycle; Carbon dioxide; Carbon Dioxide - metabolism; Carbon fixation; Catalytic Domain; Chemical reactions; Clostridium - enzymology; Coenzyme A; Crystallography, X-Ray; Electron microscopy; Electron Transport; Iron-Sulfur Proteins - chemistry; Iron-Sulfur Proteins - metabolism; Life Sciences; Microorganisms; Multienzyme Complexes - chemistry; Multienzyme Complexes - metabolism; Oxidation-Reduction; Protein Conformation
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.adr9672

In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO 2 ) is fixed in a multistep process that ends with acetyl–coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural 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, which is crucial for CO 2 fixation in anaerobic organisms. Fixing carbon dioxide into biomass is a fundamental biochemical process that has evolved just a few times in nature. In one pathway that likely dates back to the dawn of microbial life, a complex of two large enzymes, both of which contain complex metallocofactors that have been the subject of decades of study, catalyze the key reactions to make the two-carbon unit acetyl-coenzyme A from carbon dioxide. Using cryo–electron microscopy, Yin et al . determined a nearly complete set of snapshots of this enzyme complex in states corresponding to events occurring during the reaction (see the Perspective by Feng and Rees). Large conformational changes permit binding and release of a large partner protein that delivers a methyl group to the active site. —Michael A. Funk