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Figure 3: Methanogenesis pathway framework. (a) The basic structure of methanogenesis showing where the major growth substrates across all methanogens enter the pathway. The simplest methanogens are only capable of growing on CO2/H2 and/or formate while the most complex methanogens are also capable of methylotrophic and acetotrophic growth. H4S/MPT stands for tetrahydrosarcinapterin (H4SPT) and tetrahydromethanopterin (H4MPT). The former is found exclusively in Methanosarcinales whereas the latter is found in all other methanogens. (b) The hypothesized methanogenesis pathways for M. hungatei (iMhu428) [21]. Although it cannot use acetate as an energy source, the pathway to take up acetate is still present to shuttle it into gluconeogenesis. (c) The hypothesized methanogenesis pathway for M. acetivorans (iST807) [29]. The conventional CO2 reduction pathway is only run in reverse as this methanogen cannot metabolize CO2. (d) The hypothesized methanogenesis pathway for M. barkeri (iAF692) [19] which bears great resemblance to that of M. acetivorans. The major differences between the two organisms’ methanogenesis pathways lie in the electron transport chain (ETC). The specific pathways for each methanogen follow the same topological structure as the general methanogenesis illustration. Red circles are metabolites while green diamonds signify enzymatic reactions of the pathway.