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Title: Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family

Abstract

Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the AMP. To expand our understanding of the functional variety and metabolic significance of Etfs and to identify amino acid sequence motifs that potentially enable electron bifurcation, we compiled 1,314 Etf protein sequences from genome sequence databases and subjected them to informatic and structural analyses. Etfs were identified in diverse archaea and bacteria, and they clustered into five distinct well-supported groups, based on their amino acid sequences. Gene neighborhood analyses indicated that these Etf group designations largely correspond to putative differences in functionality. Etfs with the demonstrated ability to bifurcate were found to form one group, suggesting that distinct conserved aminomore » acid sequence motifs enable this capability. Indeed, structural modeling and sequence alignments revealed that identifying residues occur in the NADH- and FAD-binding regions of bifurcating Etfs. Altogether, a new classification scheme for Etf proteins that delineates putative bifurcating versus nonbifurcating members is presented and suggests that Etf-mediated bifurcation is associated with surprisingly diverse enzymes.« less

Authors:
 [1];  [1];  [2];  [3];  [4]; ORCiD logo [5];  [4];  [3]; ORCiD logo [5];  [1];  [6];  [7]
  1. Montana State Univ., Bozeman, MT (United States)
  2. Univ. of Kentucky, Lexington, KY (United States)
  3. Univ. of Georgia, Athens, GA (United States)
  4. Utah State Univ., Logan, UT (United States)
  5. Univ. of Washington, Seattle, WA (United States)
  6. Montana State Univ., Bozeman, MT (United States); Washington State Univ., Pullman, WA (United States)
  7. Philipps-Univ. Marburg, Marburg (Germany)
Publication Date:
Research Org.:
Energy Frontier Research Centers (EFRC), Washington, D.C. (United States). Center for Biological Electron Transfer and Catalysis (BETCy)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1469839
Grant/Contract Number:  
SC0012518
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Bacteriology
Additional Journal Information:
Journal Volume: 199; Journal Issue: 21; Related Information: BETCy partners with Montana State University (lead); Arizona State University; National Renewable Energy Laboratory; University of Georgia; University of Kentucky; University of Washington; Utah State University; Journal ID: ISSN 0021-9193
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; solar (fuels); biofuels (including algae and biomass); bio-inspired; hydrogen and fuel cells

Citation Formats

Garcia Costas, Amaya M., Poudel, Saroj, Miller, Anne -Frances, Schut, Gerrit J., Ledbetter, Rhesa N., Fixen, Kathryn R., Seefeldt, Lance C., Adams, Michael W. W., Harwood, Caroline S., Boyd, Eric S., Peters, John W., and Becker, Anke. Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family. United States: N. p., 2017. Web. doi:10.1128/JB.00440-17.
Garcia Costas, Amaya M., Poudel, Saroj, Miller, Anne -Frances, Schut, Gerrit J., Ledbetter, Rhesa N., Fixen, Kathryn R., Seefeldt, Lance C., Adams, Michael W. W., Harwood, Caroline S., Boyd, Eric S., Peters, John W., & Becker, Anke. Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family. United States. doi:10.1128/JB.00440-17.
Garcia Costas, Amaya M., Poudel, Saroj, Miller, Anne -Frances, Schut, Gerrit J., Ledbetter, Rhesa N., Fixen, Kathryn R., Seefeldt, Lance C., Adams, Michael W. W., Harwood, Caroline S., Boyd, Eric S., Peters, John W., and Becker, Anke. Mon . "Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family". United States. doi:10.1128/JB.00440-17. https://www.osti.gov/servlets/purl/1469839.
@article{osti_1469839,
title = {Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family},
author = {Garcia Costas, Amaya M. and Poudel, Saroj and Miller, Anne -Frances and Schut, Gerrit J. and Ledbetter, Rhesa N. and Fixen, Kathryn R. and Seefeldt, Lance C. and Adams, Michael W. W. and Harwood, Caroline S. and Boyd, Eric S. and Peters, John W. and Becker, Anke},
abstractNote = {Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the AMP. To expand our understanding of the functional variety and metabolic significance of Etfs and to identify amino acid sequence motifs that potentially enable electron bifurcation, we compiled 1,314 Etf protein sequences from genome sequence databases and subjected them to informatic and structural analyses. Etfs were identified in diverse archaea and bacteria, and they clustered into five distinct well-supported groups, based on their amino acid sequences. Gene neighborhood analyses indicated that these Etf group designations largely correspond to putative differences in functionality. Etfs with the demonstrated ability to bifurcate were found to form one group, suggesting that distinct conserved amino acid sequence motifs enable this capability. Indeed, structural modeling and sequence alignments revealed that identifying residues occur in the NADH- and FAD-binding regions of bifurcating Etfs. Altogether, a new classification scheme for Etf proteins that delineates putative bifurcating versus nonbifurcating members is presented and suggests that Etf-mediated bifurcation is associated with surprisingly diverse enzymes.},
doi = {10.1128/JB.00440-17},
journal = {Journal of Bacteriology},
number = 21,
volume = 199,
place = {United States},
year = {2017},
month = {8}
}

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