Federal Project Grant Award Summary

The University of Minnesota received a $423,500 Project Grant awarded June 1, 2026, through the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training program (CFDA 93.859). The award supports the TERPENE project, which focuses on developing innovative genomics-enabled approaches for natural product drug discovery. The research will advance technologies for titer enhancement via refactored precursor pathways by shifting from bespoke genetic reagents to universal "performance-enhancing plasmids" designed to increase secondary metabolism in recombinant Streptomyces hosts. Key innovations include the development of transgenes encoding conserved pleiotropic regulators, mutant RNA polymerases, ribosomal proteins, and pathways to overproduce precursor pools for natural product biosynthesis.

The project addresses significant bottlenecks in classical natural product discovery by streamlining plasmid creation and transgenesis protocols through high-throughput genetic engineering methodologies. Rather than requiring custom genetic reagents for each biosynthetic gene cluster targeted, the universal plasmid approach enables researchers to leverage abundant strain and genome sequence resources more efficiently. The research, conducted at the University of Minnesota's Lauderdale, Minnesota facility, is scheduled for completion by February 28, 2031, and aims to establish a new paradigm for accelerating genetics-enabled natural product drug discovery pipelines across the academic research enterprise.