With this award, the Chemistry of Life Processes Program is supporting the research of Professor Cynthia Burrows of the University of Utah. Professor Burrows hypothesizes that simple chemical transformations of RNA bases could have been the key steps in creating redox active catalysts driving early chemical systems toward a primitive metabolism. With prior NSF funding, her laboratory has shown that the oxidized base 8-oxoguanine serves as a photochemical catalyst to reductively reverse cyclobutane pyrimidine dimers to monomers. In this reaction, 8-oxoguanine acts as a flavin mimic to facilitate excited state electron transfer. Future work will explore 8-oxopurines and other redox active RNA purine and pyrimidine base derivatives for their ability to mediate oxidation and reduction reactions. For example, key reactions of early Earth must have included the ability to interconvert alcohols and aldehydes or ketones (e.g. lactate/pyruvate) using redox cofactors analogous to NADH and FADH2. Reactions such as these will be studied in RNA world-like conditions in order to test the hypothesis that simpler versions of these RNA-based cofactors could have presaged modern-day metabolism.
The broader impacts of this project are demonstrated in the unusual link between DNA damage and repair chemistry pertinent to cancer and the chemistry of primordial Earth. Photoinduced electron transfer appears to play a role in both realms, and insights from this work could be broadly applicable to other disciplines. Students trained on the project will be involved in interdisciplinary sciences including aspects of synthetic and physical organic, analytical and biochemistry. Professor Burrows has demonstrated continuing leadership in broadening participation, including programs that advance the careers of women scientists, and will continue to be active in dissemination of research to public audiences.
