Characterization of Methyl- and Acetyl-Ni Intermediates in Acetyl CoA Synthase Formed during Anaerobic CO2 and CO Fixation

The Wood-Ljungdahl Pathway is a unique biologicalmechanismof carbon dioxide and carbon monoxide fixation proposed to operatethrough nickel-based organometallic intermediates. The most unusualsteps in this metabolic cycle involve a complex of two distinct nickel-iron-sulfurproteins: CO dehydrogenase and acetyl-CoA synthase (CODH/ACS). Here,we describe the nickel-methyl and nickel-acetyl intermediates in ACScompleting the characterization of all its proposed organometallicintermediates. A single nickel site (Ni-p) within the Acluster of ACS undergoes major geometric and redox changes as it transitsthe planar Ni-p, tetrahedral Ni-p-CO andplanar Ni-p-Me and Ni-p-Ac intermediates.We propose that the Ni-p intermediates equilibrate amongdifferent redox states, driven by an electrochemical-chemical(EC) coupling process, and that geometric changes in the A-clusterlinked to large protein conformational changes control entry of COand the methyl group.

Automated summary

The Wood-Ljungdahl Pathway is a biological mechanism that fixes carbon dioxide and carbon monoxide through nickel-based organometallic intermediates. The key steps in this metabolic cycle involve CO dehydrogenase and acetyl-CoA synthase (CODH/ACS), which are complex nickel-iron-sulfur proteins. This study characterizes the nickel-methyl and nickel-acetyl intermediates in ACS, completing the understanding of all proposed organometallic intermediates. It suggests that the Ni-p intermediates undergo redox changes and equilibrate among different states, while geometric changes control the entry of CO and the methyl group.