Seven years ago we discovered that the cytoplasmic butyryl-CoA dehydrogenase-EtfAB complex from Clostridium kluyveri couples the exergonic reduction of crotonyl-CoA to butyryl-CoA with NADH and the endergonic reduction of ferredoxin with NADH via flavin-based electron bifurcation [1]. In the following years many other cytoplasmic enzyme complexes capable of energetic coupling via this novel mechanism were found in anaerobic microorganisms [2, 3]. The findings have revolutionized our understanding of the energy metabolism not only of Clostridia [4], but also of methanogenic archaea [5] and acetogenic bacteria [6]. A brief history of what recently was considered to be “the biggest breakthrough in bioenergetics of recent decades ” [7] has been published [8].

[1] F. Li, J. Hinderberger, H. Seedorf, J. Zhang, W. Buckel and R. K. Thauer, Coupled ferredoxin and crotonyl coenzyme A (CoA) reduction with NADH catalyzed by the butyryl-CoA dehydrogenasee/Etf complex from Clostridium kluyveri. J. Bacteriol. 190, 843-850 (2008)

[2] W. Buckel and R. K. Thauer, Energy conservation via electron-bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation. Biochim. Biophys. Acta 1827, 94-113 (2013).

[3] J.K. Demmer, H. Huang, S. Wang, U. Demmer‡, R. K. Thauer and U. Ermler, Insights into flavin-based electron bifurcation via the NADH-dependent reduced ferredoxin:NADP oxidoreductase structure. J. Biol. Chem. 290, 21985-21995 (2015).

[4] Y. Zheng, J. Kahnt, I. Kwon, R. Mackie and R. K. Thauer, Hydrogen formation and its regulation in Ruminococcus albus: Involvement of an electron-bifurcating [FeFe]-hydro-genase, of a non-electron-bifurcating [FeFe]-hydrogenase and of a putative H2-sensing [FeFe]-hydrogenase. J. Bacteriol. 196, 3840-3852 (2014).

[5] A.K. Kaster, J. Moll, K. Parey, and R. K. Thauer, Coupling of ferredoxin- and heterodisulfide reduction with H2 via electron bifurcation in hydrogenotrophic methanogenic archaea. Proc. Natl. Acad. Sci. USA 108, 2981-2986 (2011).

[6]J. Mock, Y. Zheng, A. P. Mueller, S. Ly, L. Tran, S. Segovia, S. Nagaraju, M. Kö pke, P. Dürre and R. K. Thauer, Energy conservation associated with ethanol formation from H2 and CO2 in Clostridium autoethanogenum involving electron bifurcation. J. Bacteriol. 197, 2965-2980 (2015).

[7] N. Lane, The Vital Question: Energy, Evolution, and the Origin of Complex life. W.W. Norton & Company, New YorK and London. page 150 (2016)

[8] R. Thauer, My lifelong passion for biochemistry and anaerobic microorganisms. Annu. Rev. Microbiol. 69, 1–30 (2015).