How flavoenzymes can light our way to sustainable energy, without breaking the laws of thermodynamics

Dr. Anne-Francese Miller

Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055

Energy conservation is vital for all life on Earth. As humanity seeks better ways to leave within our planet’s means we can find lessons and inspiration from ancient lineages of bacteria that emerged when energy was scarce. The recently-discovered process of ‘electron bifurcation’ conserves excess free energy from exergonic electron transfers and supplies strongly reducing electrons to demanding reactions such as reduction of dinitrogen. However these electrons are drawn from a more modest reductant: NADH. We are studying bifurcating electron transfer flavoproteins (BfETFs) to learn how the flavins redistribute energy among the two electrons from NADH to yield one super-reducing electron, while conserving energy and balancing the reaction with the other. Specifically, BfETFs possess two flavin adenine dinucleotides (FADs). They are chemically identical but play complementary roles. The flavin shared with canonical ETFs transfers electrons one-at-a-time to high potential acceptors (the electron transfer flavin, or ET-FAD). The FAD that executed bifurcation is absent from canonical ETFs and is called the bifurcating flavin (Bf-FAD). To learn why these chemically identical flavins perform contrasting reactions, we are probing their electronic structures by spectroscopy and quantum chemical calculations, and to understand how the protein produces these different reactivities we are deploying site-direct mutagenesis in conjunction with thermodynamic assays. Our computations also succeed in reproducing the unusual optical signature of the FAD that mediates one-electron transfer, and our mutations confirm the homology-based mechanism. Our goal is to elucidate fundamental ingredients of bifurcation that can be incorporated into to man-made materials and devices, to enable us to derive concentrated versatile power from cheap abundant renewable sources.