DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mechanistic insights into energy conservation by flavin-based electron bifurcation

Journal Article · · Nature Chemical Biology
 [1];  [2];  [1];  [3];  [4];  [5];  [4];  [4];  [3];  [3];  [4];  [2]; ORCiD logo [5]; ORCiD logo [1];  [3];  [6]
  1. National Renewable Energy Lab. (NREL), Golden, CO (United States)
  2. Arizona State Univ., Tempe, AZ (United States)
  3. Univ. of Georgia, Athens, GA (United States)
  4. Montana State Univ., Bozeman, MT (United States)
  5. Univ. of Kentucky, Lexington, KY (United States)
  6. Montana State Univ., Bozeman, MT (United States); Washington State Univ., Pullman, WA (United States)

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. As a result, 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.

Research Organization:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Grant/Contract Number:
AC36-08GO28308
OSTI ID:
1358334
Report Number(s):
NREL/JA--2700-67530
Journal Information:
Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 6 Vol. 13; ISSN 1552-4450
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (45)

Redox bifurcations: Mechanisms and importance to life now, and at its origin: A widespread means of energy conversion in biology unfolds… journal November 2011
Novel structure and redox chemistry of the prosthetic groups of the iron-sulfur flavoprotein sulfide dehydrogenase from Pyrococcus furiosus; evidence for a [2Fe-2S] cluster with Asp(Cys)3 ligands journal August 2000
Bathocuproine-assisted reduction of copper(II) by human albumin journal February 2000
Semi-continuum electrostatic calculations of redox potentials in photosystem I journal May 2008
Energetics of the one-electron reduction steps of riboflavin, FMN and FAD to their fully reduced forms journal January 1983
Energy conservation by bifurcated electron-transfer in the cytochrome-bc1 complex journal July 1996
The protonmotive Q cycle: A general formulation journal November 1975
Bifurcated ubihydroquinone oxidation in the cytochrome bc 1 complex by proton-gated charge transfer journal May 1996
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension journal April 1989
Heterologous expression and properties of the γ-subunit of the Fe-only hydrogenase from Thermotoga maritima journal June 2001
On the Nature of the Spin Coupling between the Iron-Sulfur Clusters in the Eight-Iron Ferredoxins journal July 1974
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Marcus treatment of endergonic reactions: A commentary journal October 2007
Activated Q-cycle as a common mechanism for cytochrome bc1 and cytochrome b6f complexes journal December 2010
Energy conservation via electron bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation journal February 2013
Electron bifurcation journal April 2016
EasySpin, a comprehensive software package for spectral simulation and analysis in EPR journal January 2006
QSoas: A Versatile Software for Data Analysis journal May 2016
Thermodynamic Basis of Electron Transfer in Dihydroorotate Dehydrogenase B from Lactococcus lactis :  Analysis by Potentiometry, EPR Spectroscopy, and ENDOR Spectroscopy journal June 2004
Effect of Iron-Sulfur Cluster Environment in Modulating the Thermodynamic Properties and Biological Function of Ferredoxin from Pyrococcus furiosus journal May 1998
Natural engineering principles of electron tunnelling in biological oxidation–reduction journal November 1999
Exploiting microbial hyperthermophilicity to produce an industrial chemical, using hydrogen and carbon dioxide journal March 2013
Covalently bound phosphate residues in bovine milk xanthine oxidase and in glucose oxidase from Aspergillus niger: a reevaluation journal September 1989
Studies on the Mechanism of Electron Bifurcation Catalyzed by Electron Transferring Flavoprotein (Etf) and Butyryl-CoA Dehydrogenase (Bcd) of Acidaminococcus fermentans journal December 2013
Insights into Flavin-based Electron Bifurcation via the NADH-dependent Reduced Ferredoxin:NADP Oxidoreductase Structure journal July 2015
Reduction of Flavodoxin by Electron Bifurcation and Sodium Ion-dependent Reoxidation by NAD + Catalyzed by Ferredoxin-NAD + Reductase (Rnf) journal April 2016
ClusPro: an automated docking and discrimination method for the prediction of protein complexes journal December 2003
FRODOCK: a new approach for fast rotational protein–protein docking journal July 2009
PRISM: a web server and repository for prediction of protein–protein interactions and modeling their 3D complexes journal May 2014
Phaser crystallographic software journal July 2007
Coot model-building tools for molecular graphics journal November 2004
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard journal December 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Reduction of ferredoxin or oxygen by flavin-based electron bifurcation in Megasphaera elsdenii journal May 2015
Excited-State Dynamics of Fully Reduced Flavins and Flavoenzymes Studied at Subpicosecond Time Resolution journal August 1998
Titanium (III) citrate as a nontoxic oxidation-reduction buffering system for the culture of obligate anaerobes journal December 1976
Natural Competence in the Hyperthermophilic Archaeon Pyrococcus furiosus Facilitates Genetic Manipulation: Construction of Markerless Deletions of Genes Encoding the Two Cytoplasmic Hydrogenases journal February 2011
Electron Bifurcation Involved in the Energy Metabolism of the Acetogenic Bacterium Moorella thermoacetica Growing on Glucose or H2 plus CO2 journal May 2012
NADP+ Reduction with Reduced Ferredoxin and NADP+ Reduction with NADH Are Coupled via an Electron-Bifurcating Enzyme Complex in Clostridium kluyveri journal July 2010
Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri journal November 2007
Energy Conservation via Electron-Transferring Flavoprotein in Anaerobic Bacteria journal November 2007
The Iron-Hydrogenase of Thermotoga maritima Utilizes Ferredoxin and NADH Synergistically: a New Perspective on Anaerobic Hydrogen Production journal May 2009
A novel and remarkably thermostable ferredoxin from the hyperthermophilic archaebacterium Pyrococcus furiosus. journal June 1989
The Cytochrome bc 1 Complex: Function in the Context of Structure journal March 2004
Biomolecular EPR Spectroscopy book December 2008

Cited By (25)

The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile journal November 2017
Author Correction: Hydrogen-based metabolism as an ancestral trait in lineages sibling to the Cyanobacteria journal March 2019
Methane on Mars and Habitability: Challenges and Responses journal October 2018
Distinct Physiological Roles of the Three Ferredoxins Encoded in the Hyperthermophilic Archaeon Thermococcus kodakarensis journal March 2019
Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA journal January 2020
Electron Bifurcation and Confurcation in Methanogenesis and Reverse Methanogenesis journal June 2018
The Role of Mass Spectrometry in Structural Studies of Flavin-Based Electron Bifurcating Enzymes journal July 2018
Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes journal August 2018
Distribution, Evolution, Catalytic Mechanism, and Physiological Functions of the Flavin-Based Electron-Bifurcating NADH-Dependent Reduced Ferredoxin: NADP+ Oxidoreductase journal March 2019
Electron Bifurcation Makes the Puzzle Pieces Fall Energetically into Place in Methanogenic Energy Conservation journal November 2017
The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile journal November 2017
Hydrogen-based metabolism as an ancestral trait in lineages sibling to the Cyanobacteria journal January 2019
Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors journal May 2019
On the nature of organic and inorganic centers that bifurcate electrons, coupling exergonic and endergonic oxidation–reduction reactions journal January 2018
Electron bifurcation: progress and grand challenges journal January 2019
Spectroscopic, thermodynamic and computational evidence of the locations of the FADs in the nitrogen fixation-associated electron transfer flavoprotein journal January 2019
Revealing the transient conformations of a single flavin adenine dinucleotide using an aerolysin nanopore journal January 2019
Two functionally distinct NADP + -dependent ferredoxin oxidoreductases maintain the primary redox balance of Pyrococcus furiosus journal July 2017
The catalytic mechanism of electron-bifurcating electron transfer flavoproteins (ETFs) involves an intermediary complex with NAD + journal December 2018
A physiological perspective on the origin and evolution of photosynthesis journal November 2017
DsrL mediates electron transfer between NADH and rDsrAB in Allochromatium vinosum journal December 2019
Homoacetogenesis in Deep-Sea Chloroflexi , as Inferred by Single-Cell Genomics, Provides a Link to Reductive Dehalogenation in Terrestrial Dehalococcoidetes journal December 2017
Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA journal January 2020
Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD+ (Rnf) as Electron Acceptors: A Historical Review journal March 2018
Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes journal August 2018

Similar Records

A new era for electron bifurcation
Journal Article · Wed Aug 01 00:00:00 EDT 2018 · Current Opinion in Chemical Biology · OSTI ID:1465646

Electron Bifurcation
Journal Article · Fri Apr 01 00:00:00 EDT 2016 · Current Opinion in Chemical Biology · OSTI ID:1247119

The Role of Mass Spectrometry in Structural Studies of Flavin-Based Electron Bifurcating Enzymes
Journal Article · Thu Jul 05 00:00:00 EDT 2018 · Frontiers in Microbiology · OSTI ID:1510453