CAREER: Nucleic Acid-Catalyzed Halogenations

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professor Engelhart from the University of Minnesota-Twin Cities is studying the development of new chemical reactions that are catalyzed by enzymes made of RNA and heme. These reactions form bonds between carbon atoms and halogen atoms. Many RNA enzymes have been discovered, but enzymes that perform such a transformation are a new area of investigation in RNA enzymology. This study could provide insights into the potential roles for this reaction in living systems, as well as in chemical synthesis and biotechnology applications. This project is also integrated into an education and outreach program. This program will engage the broader public through distribution of laboratory kits. It will also engage lifelong learners (age 50+) in a partnership with the Osher Lifelong Learning Institute at the University of Minnesota by introducing them to new aspects of RNA biochemistry through a short course and augmented reality educational tools. This project seeks to investigate a new functional RNA-catalyzed reaction: halogenation by ribozymes that bind heme. In this project, the team proposes to characterize the range of heme ribozyme-catalyzed halogenations that are possible and work towards obtaining new heme-binding ribozymes to better understand which sequences perform halogenation reactions. The project team will use a range of biophysical and molecular techniques, including NMR, ESI, in vitro selection, directed evolution, and next-generation sequencing to characterize the ribozymes. Information gained from this study could provide new insights into the range of chemical transformations that RNA catalysts can promote and the enzymology of these catalysts. 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.