Advancing Understanding of Methyl Coenzyme-M Reductase

The Science

Methyl coenzyme-M reductase (MCR) is an enzyme involved in biological methane conversion. Scientists have studied MCR for over a decade to better understand how it reacts with methane to generate new carbon-oxygen bonds. However, its nickel-based active site is difficult to access experimentally, necessitating a combined experimental and computational approach. This review article summarizes the current understanding of the structure of MCR and the mechanism of MCR catalyzed reactions, including the likely substrate binding order and thermodynamically favored methyl radical mechanism.

The Impact

Effectively using methane resources requires a deep understanding of its formation and breakdown. MCR plays a key role in biological methane metabolism and its function can inform new routes to methane-related synthesis, leading to bioinspired and on-demand methane synthesis. As MCR uses a nickel center rather than precious metals, insights into its mechanism may help researchers design new catalysts based on Earth-abundant and domestically accessible materials to increase energy security. Future work characterizing the MCR active form is still needed, which could offer additional information on alternate mechanisms for methane production.

Summary

MCR plays a central role in methane metabolism for living organisms, facilitating the final step in methane production and the initial step in methane oxidation. This positions it as a crucial target for bioinspired synthesis methods aimed at making and breaking bonds in methane. Methane serves as a significant source of domestic energy in the United States and holds promise as an energy storage molecule due to the existing infrastructure. Researchers have extensively investigated MCR to achieve a thorough understanding of its mechanism. A combination of computational and experimental techniques has revealed several vital aspects of the MCR mechanism, providing insights into substrate binding and identifying the energetic favorability of the methyl radical mechanism under realistic reaction conditions. This knowledge has been acquired through systematic studies over a decade of cross-disciplinary collaboration. Although considerable progress has been made in understanding how MCR functions, much work remains to be done in characterizing the catalytically active MCR species. An improved understanding of MCR catalyzed reactions can assist researchers in developing more effective and efficient methane conversion technologies, tapping into the energy storage capabilities of this important molecule.

Contact

Bojana Ginovska, Pacific Northwest National Laboratory, bojana.ginovska@pnnl.gov 

Simone Raugei, Pacific Northwest National Laboratory, simone.raugei@pnnl.gov

Funding

S.R. and B.G. acknowledge support from the Department of Energy (DOE), Basic Energy Sciences program, CSGB Physical Biosciences program (BES) under FWP 66476. Pacific Northwest National Laboratory is operated by Battelle for DOE under contract number DEAC05-75RL01830. This work also was supported by the Physical Biosciences program within BES by contract DE-FG02-08ER15931 (S.W.R. and CO). R.S. acknowledges support from DOE, BES CSGB Physical Biosciences program under FWP100593.