Four overlapping methanogenic pathways found in M. barkeri. Many methanogens reduce CO2 to methane by using electrons derived from the oxidation of H2 (hydrogenotrophic pathway, shown in red in A). Alternatively, acetate can be split into a methyl group and an enzyme-bound carbonyl moiety. The latter is oxidized to CO2 to provide the electrons required for reduction of the methyl group to methane (aceticlastic pathway, shown in blue in B). C-1 compounds such as methanol or methyl-amines can also be disproportionated to CO2 and methane. In this pathway, one molecule of the C-1 compound is oxidized to provide electrons for reduction of three additional molecules to methane (methylotrophic pathway, shown in green in C). Finally, C-1 compounds can be reduced by using electrons derived from hydrogen oxidation (methyl reduction pathway, shown in orange in D). Steps not required by each pathway are shaded gray. The step catalyzed by the Mtr protein is indicated: note that this enzyme is predicted to be required for all pathways except the methyl-reduction pathway. CHO-MF, formyl-methanofuran; CHO-H4SPT, formyl-tetrahydrosarcinapterin; CH≡H4SPT, methenyl-tetrahydrosarcinapterin; , methylene-tetrahydrosarcinapterin; CH3-H4SPT, methyl-tetrahydrosarcinapterin; CH3-CoM, methyl-coenzyme M; CoM, coenzyme M; CoB, coenzyme B; CoM-CoB, mixed disulfide of CoM and CoB; Mph/MphH2, oxidized and reduced methanophenazine; F420/F420H2, oxidized and reduced Factor 420; Fd(ox)/Fd(red), oxidized and reduced ferredoxin; Ac, acetate; Ac-Pi, acetyl-phosphate; Ac-CoA, acetyl-CoA; Ech, ferredoxin-dependent hydrogenase; Frh, F420-dependent hydrogenase; Vho, methanophenazine-dependent hydrogenase; Fpo, F420 dehydrogenase.