Intermediates in the Catalytic Cycle of Methyl Coenzyme M Reductase: Isotope Exchange is Consistent with Formation of a σ‐Alkane–Nickel Complex

The key nickel enzyme for methanogenesis (MCR) catalyzes the formation of CH3D and CH2D2 in a deuterated medium. CH2D2 is formed by an exchange of deuterium into the S-methyl group of the substrate. Deuterium is incorporated at both carbon atoms of the S-ethyl group of ethyl coenzyme M, and a 13C label is rapidly scrambled within the ethyl group (see scheme). Thus, at least one intermediate is formed and the isotope exchange pattern is consistent with formation of a σ-alkane–nickel complex.