Methanogenic archaea exploit excess hydrogen to convert carbon dioxide into methane through a multi-enzymatic pathway, the last step of which is catalyzed by methyl-coenzyme M reductase (MCR). These archaea collectively make a gigaton of methane each year, including in your gut right now! MCR is the second most abundant enzyme on Earth but we still do not know precisely how it makes and breaks methane. In this project, we prepare small-molecule nickel complexes as models for the MCR active site in its different states. If we compare data for these well-defined models to those for the less tractable enzyme, we can get clues regarding the plausibility of structures proposed for the enzyme states.
The MCR active site features a macrocyclic nickel cofactor called F430, which is anchored to the polypeptide through a glutamine reside. The nickel site can bind the heterodisulfide CoAS-SCoM, which comprises the two coenzymes A and M linked by a sulfur-sulfur bond, as pictured. Fission of this bond affords a reactive state that reversibly splits methane. It is precisely this chemistry that we are most keen to recapitulate with synthetic complexes.