Electron bifurcation: progress and grand challenges.

Electron bifurcation moves electrons from a two-electron donor to reduce two spatially separated one-electron acceptors. If one of the electrons reduces a high-potential (lower energy) acceptor, then the other electron may proceed "uphill" to reduce a low-potential (higher energy) acceptor. This mechanism is now considered the third mode of energy transduction in biology, and offers promise for the development of novel bioinspired energy conversion strategies. Nature uses electron bifurcation to realize highly sought-after reactions: reversible CO2 reduction, nitrogen fixation, and hydrogen production. In this review, we summarize the current understanding of electron bifurcation, including both recent progress and outstanding questions in understanding and developing artificial electron bifurcation systems.

[1]  Abhigna Polavarapu,et al.  Understanding intrinsically irreversible, non-Nernstian, two-electron redox processes: a combined experimental and computational study of the electrochemical activation of platinum(IV) antitumor prodrugs. , 2014, Journal of the American Chemical Society.

[2]  A. Crofts The Q-cycle – A Personal Perspective , 2004, Photosynthesis Research.

[3]  V. Müller,et al.  An Electron-bifurcating Caffeyl-CoA Reductase* , 2013, The Journal of Biological Chemistry.

[4]  David N. Beratan,et al.  Biochemistry and Theory of Proton-Coupled Electron Transfer , 2014, Chemical reviews.

[5]  Peng Zhang,et al.  Electron Bifurcation: Thermodynamics and Kinetics of Two-Electron Brokering in Biological Redox Chemistry. , 2017, Accounts of chemical research.

[6]  J. W. Peters,et al.  Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family , 2017, Journal of bacteriology.

[7]  David N Beratan,et al.  On the nature of organic and inorganic centers that bifurcate electrons, coupling exergonic and endergonic oxidation-reduction reactions. , 2018, Chemical communications.

[8]  Peng Zhang,et al.  A new era for electron bifurcation. , 2018, Current opinion in chemical biology.

[9]  P. Dutton,et al.  Fixing the Q cycle. , 2005, Trends in biochemical sciences.

[10]  Rudolph A. Marcus,et al.  On the Theory of Oxidation‐Reduction Reactions Involving Electron Transfer. I , 1956 .

[11]  J. W. Peters,et al.  The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis. , 2017, Biochemistry.

[12]  Ville R. I. Kaila Long-range proton-coupled electron transfer in biological energy conversion: towards mechanistic understanding of respiratory complex I , 2018, Journal of The Royal Society Interface.

[13]  Anne-Kristin Kaster,et al.  Coupling of ferredoxin and heterodisulfide reduction via electron bifurcation in hydrogenotrophic methanogenic archaea , 2011, Proceedings of the National Academy of Sciences.

[14]  W. Buckel,et al.  Reduction of ferredoxin or oxygen by flavin‐based electron bifurcation in Megasphaera elsdenii , 2015, The FEBS Journal.

[15]  Richard L. Lord,et al.  Ring-slippage and multielectron redox properties of Fe/Ru/Os-bis(arene) complexes: does hapticity change really cause potential inversion? , 2011, Journal of the American Chemical Society.

[16]  R. Thauer My Lifelong Passion for Biochemistry and Anaerobic Microorganisms. , 2015, Annual review of microbiology.

[17]  Filipa L. Sousa,et al.  Native metals, electron bifurcation, and CO2 reduction in early biochemical evolution. , 2018, Current opinion in microbiology.

[18]  W. Lubitz,et al.  Proton Coupled Electronic Rearrangement within the H-Cluster as an Essential Step in the Catalytic Cycle of [FeFe] Hydrogenases. , 2017, Journal of the American Chemical Society.

[19]  M. Bowman,et al.  A Caged, Destabilized, Free Radical Intermediate in the Q‐Cycle , 2013, Chembiochem : a European journal of chemical biology.

[20]  J. W. Peters,et al.  Electron Bifurcation Makes the Puzzle Pieces Fall Energetically into Place in Methanogenic Energy Conservation , 2017, Chembiochem : a European journal of chemical biology.

[21]  Tammer A. Farid,et al.  Electron tunneling chains of mitochondria. , 2006, Biochimica et biophysica acta.

[22]  Dennis H. Evans One-electron and two-electron transfers in electrochemistry and homogeneous solution reactions. , 2008, Chemical reviews.

[23]  Dennis H. Evans,et al.  Inverted potentials in two-electron processes in organic electrochemistry , 1996 .

[24]  R. Thauer,et al.  NADP+ Reduction with Reduced Ferredoxin and NADP+ Reduction with NADH Are Coupled via an Electron-Bifurcating Enzyme Complex in Clostridium kluyveri , 2010, Journal of bacteriology.

[25]  S. Hammes-Schiffer,et al.  Theory of coupled electron and proton transfer reactions. , 2010, Chemical reviews.

[26]  A. Crofts,et al.  The Q-Cycle Mechanism of the bc1 Complex: A Biologist's Perspective on Atomistic Studies. , 2017, The journal of physical chemistry. B.

[27]  J. W. Peters,et al.  The catalytic mechanism of electron-bifurcating electron transfer flavoproteins (ETFs) involves an intermediary complex with NAD+ , 2018, The Journal of Biological Chemistry.

[28]  P. Mitchell,et al.  Possible molecular mechanisms of the protonmotive function of cytochrome systems. , 1976, Journal of theoretical biology.

[29]  Volker Müller,et al.  Electron Bifurcation: A Long-Hidden Energy-Coupling Mechanism. , 2018, Annual review of microbiology.

[30]  J. Mayer,et al.  A Continuum of Proton-Coupled Electron Transfer Reactivity. , 2018, Accounts of chemical research.

[31]  Sarah E. Chobot,et al.  Quinone and non-quinone redox couples in Complex III , 2008, Journal of bioenergetics and biomembranes.

[32]  R. Thauer,et al.  Insights into Flavin-based Electron Bifurcation via the NADH-dependent Reduced Ferredoxin:NADP Oxidoreductase Structure* , 2015, The Journal of Biological Chemistry.

[33]  J. W. Peters,et al.  Mechanistic insights into energy conservation by flavin-based electron bifurcation. , 2017, Nature chemical biology.

[34]  J. Berden,et al.  Oxidoreduction of cytochrome b in the presence of antimycin. , 1972, Biochimica et biophysica acta.

[35]  Haiyan Huang,et al.  Distribution, Evolution, Catalytic Mechanism, and Physiological Functions of the Flavin-Based Electron-Bifurcating NADH-Dependent Reduced Ferredoxin: NADP+ Oxidoreductase , 2019, Front. Microbiol..

[36]  B. Dijkstra,et al.  A crystallographic study of Cys69Ala flavodoxin II from Azotobacter vinelandii: Structural determinants of redox potential , 2005, Protein science : a publication of the Protein Society.

[37]  R. Thauer,et al.  Energy conservation via electron bifurcating ferredoxin reduction and proton/Na(+) translocating ferredoxin oxidation. , 2013, Biochimica et biophysica acta.

[38]  Klaus Schulten,et al.  The mechanism of ubihydroquinone oxidation at the Qo-site of the cytochrome bc1 complex. , 2013, Biochimica et biophysica acta.

[39]  M. Adams,et al.  The Iron-Hydrogenase of Thermotoga maritima Utilizes Ferredoxin and NADH Synergistically: a New Perspective on Anaerobic Hydrogen Production , 2009, Journal of bacteriology.

[40]  U. Ermler,et al.  Molecular basis of the flavin‐based electron‐bifurcating caffeyl‐CoA reductase reaction , 2018, FEBS letters.

[41]  P. Dutton,et al.  Exposing the complex III Qo semiquinone radical. , 2007, Biochimica et biophysica acta.

[42]  Michael J. Russell,et al.  On the Natural History of Flavin-Based Electron Bifurcation , 2018, Front. Microbiol..

[43]  The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile , 2017, Nature Communications.

[44]  A. Crofts,et al.  Proton-coupled electron transfer at the Qo-site of the bc1 complex controls the rate of ubihydroquinone oxidation. , 2004, Biochimica et biophysica acta.

[45]  E. Jayamani,et al.  Energy Conservation via Electron-Transferring Flavoprotein in Anaerobic Bacteria , 2007, Journal of bacteriology.

[46]  P. Dutton,et al.  Reversible redox energy coupling in electron transfer chains , 2004, Nature.

[47]  E. Boyd,et al.  Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes , 2018, Front. Microbiol..

[48]  J. Ferry,et al.  Electron Bifurcation and Confurcation in Methanogenesis and Reverse Methanogenesis , 2018, Front. Microbiol..

[49]  R. Thauer,et al.  Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD+ (Rnf) as Electron Acceptors: A Historical Review , 2018, Front. Microbiol..

[50]  M. Russell,et al.  Redox bifurcations: Mechanisms and importance to life now, and at its origin , 2012, BioEssays : news and reviews in molecular, cellular and developmental biology.

[51]  J. W. Peters,et al.  Electron bifurcation. , 2016, Current opinion in chemical biology.

[52]  J. W. Peters,et al.  The catalytic mechanism of electron-bifurcating electron transfer flavoproteins (ETFs) involves an intermediary complex with NAD. , 2019, Journal of Biological Chemistry.

[53]  P. Mitchell,et al.  The protonmotive Q cycle: A general formulation , 1975, FEBS letters.

[54]  M. Sola,et al.  Redox properties of cytochrome c. , 2001, Antioxidants & redox signaling.

[55]  R. Little,et al.  Two-Electron Reactions in Organic and Organometallic Electrochemistry. , 1999 .

[56]  R. Thauer,et al.  Flavin-Based Electron Bifurcation, A New Mechanism of Biological Energy Coupling. , 2018, Chemical reviews.

[57]  Harry B Gray,et al.  Electron tunneling through proteins , 2003, Quarterly Reviews of Biophysics.

[58]  Daniel Picot,et al.  From low- to high-potential bioenergetic chains: Thermodynamic constraints of Q-cycle function. , 2016, Biochimica et biophysica acta.

[59]  J. W. Peters,et al.  Investigations on the role of proton-coupled electron transfer in hydrogen activation by [FeFe]-hydrogenase. , 2014, Journal of the American Chemical Society.

[60]  A. Crofts,et al.  Structure and function of the cytochrome bc1 complex of mitochondria and photosynthetic bacteria. , 1998, Current opinion in structural biology.