Deconstructing F430: quantum chemical perspectives of biological methanogenesis

What stabilizes the unique Ni(I) state of the active form of coenzyme F(430) and of methylcoenzyme M reductase, the enzyme responsible for the last methane-evolving step of biological methanogenesis? A survey of F(430) model compounds suggests that the monoanionic nature of the F(430) ligand goes a long way toward explaining the stability of Ni(I) F(430). Second, nature appears to have manipulated the stereochemistry of the macrocycle, particularly that of the 12- and 13- substituents, so that the cofactor is sterically constrained against ruffling and forced to adopt a relatively planar conformation with long Ni--N distances. Third, the carbonyl substituent at the 15-meso position electronically stabilizes the Ni(I) state of the cofactor. With regard to the mechanism of methylcoenzyme M reductase, the most reasonable mechanism, in our opinion, involves a Ni(I)-mediated homolytic cleavage of the S--CH(3) bond in methylcoenzyme M, followed immediately by the quenching of the methyl radical by coenzyme B (a thiol) to produce methane.