Summary of Federal Grant Award

The University of California, San Diego received a $369,347 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective July 1, 2026 through June 30, 2031. This award supports high-resolution structural analysis of megasynthases using cryo-electron microscopy (cryo-EM). The research focuses on developing and applying molecular tools and probes to capture state-trapped configurations of large Type I multimodular megasynthases, enabling previously unattainable high-resolution structures of these complex enzyme complexes involved in polyketide synthase and non-ribosomal peptide synthetase pathways.

The project deliverables include the expansion of existing probes and technologies for structural elucidation of megasynthases that produce clinically important natural products, with initial focus on amphotericin B and cyclosporine A biosynthetic pathways. By unraveling the structural complexity of these carrier protein-dependent multienzyme systems, the research is intended to provide unprecedented molecular visualization of protein-protein interactions and enable the development of designed metabolic pathways with applications across infectious disease, metabolic, immunomodulatory, and oncological drug discovery and development.