RUI: Chemoenzymatic fluorination of aromatic compounds

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, S. Eric Nybo of Ferris State University is studying the development of enzymatic tools for incorporating fluorine atoms into natural products. Fluorine is abundant in the earth’s crust and exhibits important chemical properties for pharmaceuticals and agricultural chemicals. However, few examples of fluorinated natural products exist, and nature’s strategies for synthesizing complex natural products from simple fluoride ions are not fully understood. The proposed research will involve undergraduates in studying the biosynthesis of organofluorine molecules by cloning enzymes from bacterial pathways. The students will be trained in NMR spectroscopy using a low-field benchtop NMR and generate new natural products with carbon-fluorine bonds. The students will create explainer videos on social media introducing NMR spectroscopy. The project will also feature a collaboration with undergraduates from nearby Delta College. The focus of this research project is the development of new chemoenzymatic strategies for incorporating carbon-fluorine bonds into aromatic polyketides. A goal of the proposed work is to clarify nature’s enzymatic strategies for converting inorganic fluoride ions to fluoroacetate by heterologously expressing the fluorinase operon in Escherichia coli. The project will involve investigation of acyl-CoA (coenzyme A) ligase enzymes for activating organofluorine building blocks to the corresponding fluoroacyl thioesters. Dr. Nybo and his students at Ferris State University will also investigate type II and type III polyketide synthase enzymes capable of loading fluoroacylated intermediates and synthesizing “new to nature” polyketides. New fluorometabolites will be characterized via 19F-NMR using a benchtop NMR. These studies have the potential to provide new insights into the generation of fluorinated aromatic molecules using enzymes. 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.