Methyl-coenzyme M reductase: Model studies on pentadentate nickel complexes and a hypothetical mechanism

Methane is ultimately produced in methanogenic bacteria by the reaction of the methyl thioether-2-(methylthio)ethanesulfonate (methyl-coenzyme M; Me-CoM) with the thiol N-7-mercaptoheptanoyl-O-phospho-l-threonine (HS-HTP). As the second product, the mixed disulfide HTP-SS-CoM is formed. The enzyme methyl-coenzyme M reductase catalyzes this transformation and contains as cofactor the nickel tetrahydrocorphinoid “factor 430” (F430). The model study described here was intended to shed light on the mechanism of this last step of methanogenesis, and in particular on the role of F430. A series of nickel chelates was synthesized as models for an interaction of the sulfur containing substrates with F430. As a common feature, the model complexes posess a pentadentate ligand that positions the sulfur atom of a thioether at an axial coordination site of the nickel ion. For comparison, sulfur was replaced by oxygen in one case. The electrochemical investigation of the models revealed that electron transfer from sulfur to nickel can easily take place, oxidation of the thioether moieties occured at potentials ca. 500–600 mV lower compared to those of uncomplexed thioethers (such as thioanisole). Based on this result, a hypothetical mechanism for the catalysis effected by methyl-coenzyme M reductase is formulated. The central feature of this mechanism is the initiation of sulfur-sulfur bond formation between the two substrates by the transfer of one electron from the thiolate anion of HS-HTP to F430 [Ni(II)]. The proposed catalytic cycle is in accord with the results of earlier studies on methyl-coenzyme M reductase (substrate analogues/inhibitors, ESR studies).