Protein complexing in a methanogen suggests electron bifurcation and electron delivery from formate to heterodisulfide reductase

Kyle C. Costa, Phoebe M. Wong, Tiansong Wang, Thomas J. Lie, Jeremy A. Dodsworth, Ingrid Swanson, June A. Burn, Murray Hackett, John A. Leigh

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


In methanogenic Archaea, the final step of methanogenesis generates methane and a heterodisulfide of coenzyme M and co-enzyme B (CoM-S-S-CoB). Reduction of this heterodisulfide by heterodisulfide reductase to regenerate HS-CoM and HS-CoB is an exergonic process. Thauer et al. [Thauer, et al. 2008 Nat Rev Microbiol 6:579-591] recently suggested that in hydrogenotrophic methanogens the energy of heterodisulfide reduction powers the most endergonic reaction in the pathway, catalyzed by the formylmethanofuran dehydrogenase, via flavin-based electron bifurcation. Here we present evidence that these two steps in methanogenesis are physically linked. We identify a protein complex from the hydrogenotrophic methanogen, Methanococcus maripaludis, that contains heterodisulfide reductase, formylmethanofuran dehydrogenase, F 420-nonreducing hydrogenase, and formate dehydrogenase. In addition to establishing a physical basis for the electron-bifurcation model of energy conservation, the composition of the complex also suggests that either H 2 or formate (two alternative electron donors for methanogenesis) can donate electrons to the heterodisulfide-H2 via F420- nonreducing hydrogenase or formate via formate dehydrogenase. Electron flow from formate to the heterodisulfide rather than the use of H2 as an intermediate represents a previously unknown path of electron flow in methanogenesis.We further tested whether this path occurs by constructing a mutant lacking F420-nonreducing hydrogenase. The mutant displayed growth equal to wild-type with formate but markedly slower growth with hydrogen. The results support the model of electron bifurcation and suggest that formate, like H2, is closely integrated into the methanogenic pathway.

Original languageEnglish (US)
Pages (from-to)11050-11055
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 15 2010
Externally publishedYes


  • Archaea
  • Energy conservation
  • F-nonreducing hydrogenase
  • Formate dehydrogenase
  • Formylmethanofuran dehydrogenase

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