Mechanistic insights into energy conservation by flavin-based electron bifurcation

Carolyn E. Lubner, David P. Jennings, David W. Mulder, Gerrit J. Schut, Oleg A. Zadvornyy, John P. Hoben, Monika Tokmina-Lukaszewska, Luke Berry, Diep M. Nguyen, Gina L. Lipscomb, Brian Bothner, Anne K. Jones, Anne Frances Miller, Paul W. King, Michael W.W. Adams, John W. Peters

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


The recently realized biochemical phenomenon of energy conservation through electron bifurcation provides biology with an elegant means to maximize utilization of metabolic energy. The mechanism of coordinated coupling of exergonic and endergonic oxidation-reduction reactions by a single enzyme complex has been elucidated through optical and paramagnetic spectroscopic studies revealing unprecedented features. Pairs of electrons are bifurcated over more than 1 volt of electrochemical potential by generating a low-potential, highly energetic, unstable flavin semiquinone and directing electron flow to an iron-sulfur cluster with a highly negative potential to overcome the barrier of the endergonic half reaction. The unprecedented range of thermodynamic driving force that is generated by flavin-based electron bifurcation accounts for unique chemical reactions that are catalyzed by these enzymes.

Original languageEnglish
Pages (from-to)655-659
Number of pages5
JournalNature Chemical Biology
Issue number6
StatePublished - Jun 1 2017

Bibliographical note

Funding Information:
This work and all authors were solely supported as part of the Biological and Electron Transfer and Catalysis (BETCy) EFRC, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0012518. Use of the Stanford Synchrotron Radiation Lightsource (SSRL), SLAC National Accelerator Laboratory, is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The Proteomics, Metabolomics, and Mass Spectrometry facility at MSU received support from the Murdock Charitable Trust and NIH 5P20RR02437 of the COBRE program. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or the NIH. C.E.L., D.W.M., and P.W.K. were supported by the US Department of Energy under contract no. DE-AC36-08-GO28308 with the National Renewable Energy Laboratory.

Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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