Methyl-coenzyme M reductase (MCR) from methanogenic archaea catalyzes the final step in biological methane synthesis and the first step in in anaerobic methane oxidation (Rxn. 1). MCR contains a redox-active nickel tetrahydrocorphin (Coenzyme F₄₃₀) at its active site. The active state of MCR in the forward (methane synthesis) and reverse (methane oxidation) directions is Ni(I) (MCR_red1). We have used spectroscopic, kinetic and computational studies to characterize intermediates in the forward and reverse directions. The transition state for methane C-H bond formation/abstraction is a methyl radical sandwiched between a Ni-bound CoM and CoBSH (Fig. 1). ¹ We also describe investigations on the binding of methyl-SCoM and CoBSSCoM, substrates of MCR_red1 in the forward and reverse directions, respectively (Fig. 2).² These studies reveal the formation of Ni(I)-sulfonate complexes, prompting a significant alteration in the canonical MCR mechanism and implicating long-distance electron transfer in C-H bond formation and cleavage by MCR. These studies provide significant new information about how nature catalyzes the abstraction of H atoms from alkanes, considered to be one of the most difficult chemical reactions, given the 440 kJ/mol C-H bond dissociation energy in methane.
References
1. Wongnate, T.; Sliwa, D.; Ginovska, B.; Smith, D.; Wolf, M. W.; Lehnert, N.; Raugei, S.; Ragsdale, S. W., The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase. Science 2016, 352 (6288), 953-8.
2. Patwardhan, A.; Sarangi, R.; Ginovska, B.; Raugei, S.; Ragsdale, S., Nickel-sulfonate mode of substrate binding for forward and reverse reactions of Methyl-SCoM Reductase suggest a radical mechanism involving long range electron transfer. Journal of the American Chemical Society 2021., 2021, 143 (14), 5481-5496.

Anjali Patwardhan

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