Unraveling the structure and mechanism of acetyl-coenzyme A synthase

The bifunctional Enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A (CoA) synthase (CODH/ACS) is a key Enzyme in the Wood-Ljungdahl pathway of carbon fixation. Carbon monoxide is combined with a methyl group and ultimately converted to acetyl-CoA at a unique Ni-containing bimetallic site in the A-cluster of this Enzyme. Despite years of extensive biochemical and spectroscopic studies and the recent report of three separate crystal structures, the mechanism by which acetyl-CoA is synthesized is still unknown. Over the past two years there have been a number of significant developments regarding ACS. This Account critically examines these recent developments and especially focuses on those areas that are still a matter of debate.