Protein Complexing in a Methanogen Suggests Electron Bifurcation and Electron Delivery From Formate to Heterodisulfide Reductase

Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11050-5. doi: 10.1073/pnas.1003653107. Epub 2010 Jun 1.


In methanogenic Archaea, the final step of methanogenesis generates methane and a heterodisulfide of coenzyme M and coenzyme 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-H(2) via F(420)-nonreducing hydrogenase or formate via formate dehydrogenase. Electron flow from formate to the heterodisulfide rather than the use of H(2) 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 F(420)-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 H(2), is closely integrated into the methanogenic pathway.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism
  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Base Sequence
  • DNA Primers / genetics
  • Electron Transport*
  • Formate Dehydrogenases / genetics
  • Formate Dehydrogenases / metabolism
  • Formates / metabolism
  • Methanococcus / genetics
  • Methanococcus / growth & development
  • Methanococcus / metabolism*
  • Models, Biological
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Multiprotein Complexes
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*


  • Archaeal Proteins
  • DNA Primers
  • Formates
  • Multienzyme Complexes
  • Multiprotein Complexes
  • formic acid
  • Oxidoreductases
  • Alcohol Oxidoreductases
  • coenzyme F420-dependent alcohol dehydrogenase
  • heterodisulfide reductase
  • Formate Dehydrogenases
  • Aldehyde Oxidoreductases
  • formylmethanofuran dehydrogenase