An Uncharacteristically Low-Potential Flavin Governs the Energy Landscape of Electron Bifurcation

Courtney Wise, Anastasia Ledinina, David Mulder, Katherine Chou, John Peters, Paul King, Carolyn Lubner

Research output: Contribution to journalArticlepeer-review

7 Scopus Citations


Electron bifurcation, an energy-conserving process utilized extensively throughout all domains of life, represents an elegant means of generating high-energy products from substrates with less reducing potential. The coordinated coupling of exergonic and endergonic reactions has been shown to operate over an electrochemical potential of ∼1.3 V through the activity of a unique flavin cofactor in the enzyme NADH-dependent ferredoxin-NADP+ oxidoreductase I. The inferred energy landscape has features unprecedented in biochemistry and presents novel energetic challenges, the most intriguing being a large thermodynamically uphill step for the first electron transfer of the bifurcation reaction. However, ambiguities in the energy landscape at the bifurcating site deriving from overlapping flavin spectral signatures have impeded a comprehensive understanding of the specific mechanistic contributions afforded by thermodynamic and kinetic factors. Here, we elucidate an uncharacteristically low two-electron potential of the bifurcating flavin, resolving the energetic challenge of the first bifurcation event.

Original languageAmerican English
Article numbere2117882119
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - 22 Mar 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 the Author(s).

NREL Publication Number

  • NREL/JA-2700-77008


  • Biophysics
  • Electron bifurcation
  • Energy conservation
  • Flavoenzyme
  • Thermodynamics


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