Electron Bifurcation and Confurcation in Methanogenesis and Reverse Methanogenesis.

Reduction of the disulfide of coenzyme M and coenzyme B (CoMS-SCoB) by heterodisulfide reductases (HdrED and HdrABC) is the final step in all methanogenic pathways. Flavin-based electron bifurcation (FBEB) by soluble HdrABC homologs play additional roles in driving essential endergonic reactions at the expense of the exergonic reduction of CoMS-SCoM. In the first step of the CO reduction pathway, HdrABC complexed with hydrogenase or formate dehydrogenase generates reduced ferredoxin (Fdx) for the endergonic reduction of CO coupled to the exergonic reduction of CoMS-SCoB dependent on FBEB of electrons from H or formate. Roles for HdrABC:hydrogenase complexes are also proposed for pathways wherein the methyl group of methanol is reduced to methane with electrons from H. The HdrABC complexes catalyze FBEB-dependent oxidation of H for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB. The Fdx supplies electrons for reduction of the methyl group to methane. In H independent pathways, three-fourths of the methyl groups are oxidized producing Fdx and reduced coenzyme F (FH). The FH donates electrons for reduction of the remaining methyl groups to methane requiring transfer of electrons from Fdx to F. HdrA1B1C1 is proposed to catalyze FBEB-dependent oxidation of Fdx for the endergonic reduction of F driven by the exergonic reduction of CoMS-SCoB. In H independent acetotrophic pathways, the methyl group of acetate is reduced to methane with electrons derived from oxidation of the carbonyl group mediated by Fdx. Electron transport involves a membrane-bound complex (Rnf) that oxidizes Fdx and generates a Na gradient driving ATP synthesis. It is postulated that F is reduced by Rnf requiring HdrA2B2C2 catalyzing FBEB-dependent oxidation of FH for the endergonic reduction of Fdx driven by the exergonic reduction of CoMS-SCoB. The Fdx is recycled by Rnf and HdrA2B2C2 thereby conserving energy. The HdrA2B2C2 is also proposed to play a role in Fe(III)-dependent reverse methanogenesis. A flavin-based electron confurcating (FBEC) HdrABC complex is proposed for nitrate-dependent reverse methanogenesis in which the oxidation of CoM-SH/CoB-SH and Fdx is coupled to reduction of F. The FH donates electrons to a membrane complex that generates a proton gradient driving ATP synthesis.