3.D.8 The Na⁺ or H⁺ Pumping Formyl Methanofuran Dehydrogenase (FMF-DH) Family

FMF-DH in Methanosarcina barkeri couples Na+ transport to the reversible CO2 reduction-dependent formylation of the archaeal cofactor, methanofuran (MF). This enzyme thus initiates methanogenesis during growth in H2 and CO2, but it is also required for methanol and methylamine utilization, in which case formyl methanofuran is oxidized to CO2 and methanofuran. During CO2 reduction to CH4, a *µ (Na+) is established when the Na+/H+ antiporter is inhibited. Formaldehyde reduction to CH4 is coupled to the extrusion of 4Na+, catalyzed by the H4MPT:HS-CoM methyl transferase (TC# 10.1). However, about 2Na+ are consumed during CO2 reduction. Consequently a net ~2Na+ are pumped per CH4 reduced. By contrast, the Methanosarcina mazei Göl FMF-DH may couple formyl MF oxidation to H+ rather than Na+ extrusion.

The M. barkeri FMF DH catalyzes extrusion of ~2Na+ per mole of formaldehyde oxidized to CO2 + 2H2, and consequently, a membrane potential of ~100mV (inside negative) builds up. This potential can be used for ATP synthesis via a Na+/H+ antiporter and a H+-translocating ATP synthase. The functions of the individual subunits in the multisubunit formyl MF dehydrogenase are not well characterized, but several are homologous to the subunits of other dehydrogenases.

The overall reaction thought to be catalyzed by FMF DH is:

formyl-MF + 2Na+ or 2H+ (in) CO2 + MF + H2 + 2Na+ or 2H+ (out)