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

Abstract

Significance Nature has long been an inspiration for materials design, as it exemplifies exquisite control of both matter and energy. Electron bifurcation, a mechanism employed in biological systems to drive thermodynamically unfavorable and energetically challenging chemical reactions, is one such example. A key feature of bifurcating enzymes is the ability of a single redox cofactor to distribute a pair of electrons across two spatially separated electron transfer pathways. Here, we report on the empirical determination of both the one-electron potential and two-electron potential of the bifurcating flavin cofactor in the NADH-dependent ferredoxin-NADP + oxidoreductase I (NfnSL) enzyme. Insights arising from the defined energy landscape of this bifurcation site may underlie the design of synthetic catalysts capable of generating high-energy intermediates.