Research Article

The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

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Science  20 May 2016:
Vol. 352, Issue 6288, pp. 953-958
DOI: 10.1126/science.aaf0616

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A radical route to making methane

Microorganisms are the main drivers of Earth's methane cycle. The enzyme ultimately responsible for biological methane production has an ambiguous mechanism because it involves difficult-to-isolate reaction intermediates. Wongnate et al. used stopped-flow and rapid freeze-quench experiments to trap a methyl radical in the active site of methyl-coenzyme M reductase (see the Perspective by Lawton and Rosenzweig). Spectroscopy demonstrated that cofactor F430 contained Ni(II), consistent with computational results. The final step of methanogenesis thus proceeds through Ni(II)-thiolate and methyl radical intermediates rather than an organometallic methyl-Ni(III) mechanism.

Science, this issue p. 953;, see also p. 892


Methyl-coenzyme M reductase, the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the biological production of more than 1 billion tons of methane per year. The mechanism of methane synthesis is thought to involve either methyl-nickel(III) or methyl radical/Ni(II)-thiolate intermediates. We employed transient kinetic, spectroscopic, and computational approaches to study the reaction between the active Ni(I) enzyme and substrates. Consistent with the methyl radical–based mechanism, there was no evidence for a methyl-Ni(III) species; furthermore, magnetic circular dichroism spectroscopy identified the Ni(II)-thiolate intermediate. Temperature-dependent transient kinetics also closely matched density functional theory predictions of the methyl radical mechanism. Identifying the key intermediate in methanogenesis provides fundamental insights to develop better catalysts for producing and activating an important fuel and potent greenhouse gas.

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