An uncharacteristically low-potential flavin governs the energy landscape of electron bifurcation

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 similar to 1.3 V through the activity of a unique flavin cofactor in the enzyme NADHdependent 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.

Automated summary

Electron bifurcation is an energy-conserving process widely utilized in biochemistry, which generates high-energy products from substrates with lower reducing potential. The energetic challenge of the first bifurcation event, with a thermodynamically uphill step, is resolved by elucidating the unusually low two-electron potential of the bifurcating flavin.