Abstract
Methanogenic archaea are the main producers of the potent greenhouse gas methane(1,2). In the methanogenic pathway from CO(2) and H(2) studied under laboratory conditions, low-potential electrons for CO(2) reduction are generated by a flavin-based electron-bifurcation reaction catalysed by heterodisulfide reductase (Hdr) complexed with the associated [NiFe]-hydrogenase (Mvh)(3-5). F(420)-reducing [NiFe]-hydrogenase (Frh) provides electrons to the methanogenic pathway through the electron carrier F(420) (ref. (6)). Here we report that under strictly nickel-limited conditions, in which the nickel concentration is similar to those often observed in natural habitats(7-11), the production of both [NiFe]-hydrogenases in Methanothermobacter marburgensis is strongly downregulated. The Frh reaction is substituted by a coupled reaction with [Fe]-hydrogenase (Hmd), and the role of Mvh is taken over by F(420)-dependent electron-donating proteins (Elp). Thus, Hmd provides all electrons for the reducing metabolism under these nickel-limited conditions. Biochemical and structural characterization of Elp-Hdr complexes confirms the electronic interaction between Elp and Hdr. The conservation of the genes encoding Elp and Hmd in CO(2)-reducing hydrogenotrophic methanogens suggests that the Hmd system is an alternative pathway for electron flow in CO(2)-reducing hydrogenotrophic methanogens under nickel-limited conditions.