Bifurcation in Context: Essential ingredients and coupling with partners

About This Grant

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Dr A.-F. Miller from the University of Kentucky is studying how electron transfer bifurcation is interfaced with other reactions in metabolic pathways of diverse organisms. Microbes can convert solar energy to a maximally useful, energy-dense form and store the energy for use after sunset. Thus, life can exploit cheap, abundant energy sources to generate high-energy fuel. The microbes achieve this two-prong performance by electron transfer bifurcation ('bifurcation'). Moreover, the microbial systems use earth-abundant metals and fully renewable materials such as proteins and vitamins that can be produced in unlimited quantities. The Miller group will apply a broad range of research tools to the examination of the properties of proteins involved in bifurcation and the conditions in which the process is efficient. Prof Miller will also offer hands-on workshops and public-friendly course modules in which chemical concepts are made accessible by drawing on the aesthetic appeal and interest of the students and the public in plant pigments and textile art. In bifurcation, the energies of two moderate-energy electrons are pooled to yield one high-energy electron. The other electron from the pair is recycled by metabolic pathways that vary from organism to organism, and in essence, balance the budget. The Miller group will survey an expanded range of bifurcating electron transfer flavoproteins (ETFs) to broaden our knowledge of what enzyme systems can conduct bifurcation, and to obtain a more complete picture of what metabolic contexts support bifurcation. The team will characterize the interactions between proteins that connect bifurcation to supporting recycling systems and investigate tuning of electron-transferring flavins' reactivities by the proteins involved. Similarly, the team will elucidate mechanism(s) used to prime the bifurcating flavin for its role. These aims will deploy the group's expertise in spectroscopy, quantum chemical calculations, protein engineering, and thermodynamic measurements. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.