Project Grant 2543564

The National Science Foundation Division of Chemistry awarded the University of Georgia Research Foundation, Inc. $420,000 on September 1, 2026, under the Mathematical and Physical Sciences program (CFDA 47.049) to investigate cytochrome P450 enzymes that catalyze aromatic nitration and crosslinking reactions during the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). The research team will elucidate the catalytic pathways of CYP-catalyzed direct nitration in the presence of molecular oxygen and nitric oxide using mechanistic probes, substrate analogs, and enzyme kinetic studies to characterize reactive intermediates. The project will also define the molecular determinants that enable closely related cytochrome P450 enzymes to selectively catalyze either tyrosine nitration or tyrosine-histidine crosslinking reactions on the same peptide substrate. The discoveries are expected to expand understanding of heme-based catalysis, uncover new enzymatic systems for peptide modification, and guide development of biocatalysts for aromatic functionalization. The project incorporates research-integrated instruction, mentoring, University of Georgia outreach programs, and public science exhibitions to strengthen STEM education and broaden participation in chemistry. Performance occurs in Athens, Georgia. The award runs through August 31, 2031.