Yin Max Dongsheng, Lemaire Olivier N, Rosas Jiménez José Guadalupe, Belhamri Mélissa, Shevchenko Anna, Hummer Gerhard, Wagner Tristan, Murphy Bonnie J
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
Max Planck Research Group Microbial Metabolism, Max Planck Institute for Marine Microbiology, Bremen, Germany.
Science. 2025 Jan 31;387(6733):498-504. doi: 10.1126/science.adr9672. Epub 2025 Jan 30.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) 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 , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO 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 fixation in anaerobic organisms.
在古老的微生物伍德-Ljungdahl途径中，二氧化碳（CO₂）通过一个多步骤过程被固定，该过程最终在双功能一氧化碳脱氢酶/乙酰辅酶A合酶复合物（CODH/ACS）处合成乙酰辅酶A（acetyl-CoA）。在这项工作中，我们展示了来自气体转化产乙酸菌的CODH/ACS的结构快照，描绘了整个反应的分子编排，包括向CODH进行电子转移以还原CO、从类咕啉铁硫蛋白（CoFeSP）伴侣向ACS活性位点进行甲基转移以及产生乙酰辅酶A。与CODH不同，多结构域的ACS会发生大的构象变化，以形成与CODH活性位点的内部连接、容纳用于甲基转移的CoFeSP并保护反应中间体。总之，这些结构使我们能够绘制出这种酶的详细反应机制，这对于厌氧生物中的CO₂固定至关重要。
