Project Grant R35GM165700

The National Institute of General Medical Sciences awarded Baylor College of Medicine $400,000 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the biochemical and structural principles underlying taxa-specific antibacterial activity in natural products.

The research focuses on two model systems to answer how taxa-specific natural products inhibit novel bacterial targets and what chemical and mechanistic features differentiate selective from broad-spectrum enzyme inhibitors. The first system studies imacidin and related taxa-specific cyclic lipopeptides as the first natural inhibitors of the lipid II flippase MurJ, a key enzyme in cell wall biogenesis. The second system examines gammanonin, a selective inhibitor of peptide deformylase that employs a new mechanism distinct from the broad-spectrum inhibitor actinonin. This research addresses the therapeutic need for targeted antibacterial agents that preserve microbiome integrity and reduce antimicrobial resistance pressure, moving beyond the historic emphasis on broad-spectrum antibiotics.

Work is performed in Houston, Texas. The period of performance runs through April 30, 2031. This is a Project Grant, a component of NIGMS's investigator-initiated research portfolio supporting basic biomedical research that advances understanding of biological processes and provides foundations for disease diagnosis, treatment, and prevention.