Postdoctoral Fellowship: PRFB: Discovery and functional exploration of nature's repurposed enzymes in specialized metabolism

Martinez Grundman, Jaime Enrique, Cambridge MA

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2024, Broadening Participation of Groups Underrepresented in Biology. The Fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. The Fellow will use multiple methods to discover new enzymes, the molecules that use common building blocks found in cells (sugar, fats, and amino acids) to generate more complex products needed for organisms to properly function, including compounds that can also be used as eco-friendly pesticides or drugs for clinical use. Through evolutionary changes that alter the gene code, some enzymes gain new functions (termed neofunctionalization). Research will be conducted to identify and characterize neofunctionalized enzymes and model systems will be used to study their functions. The work has the potential to discover useful new tools for biotechnology and medicine. The Fellow will support diverse participation in STEM by engaging in interdisciplinary collaborations, student mentoring, and leading networking groups at the postdoctoral level. This project will streamline discovery of neofunctionalized enzymes in specialized metabolism via a two-step workflow: (1) surveying available protein databases for enzymes with amino acid changes at otherwise highly conserved positions as an indication of neofunctionalization, followed by computational analyses, such as positive selection, gene clustering and expansion, and structural prediction tools to inform on functional roles; and (2) testing candidate enzymes via heterologous expression in model organisms followed by untargeted metabolomics studies, as well as rigorous characterization of pure enzymes through biochemical assays and structural methods such as X-ray crystallography and NMR spectroscopy. The Fellowship will expand understanding of novel enzymes, providing examples from which to address central questions of molecular evolution and to test strategies for rational protein design. The broader impacts of the Fellowship will be to support under-represented scientists and enable fruitful collaborations across disciplines. This will include mentoring undergraduate students from local institutes and REU programs to conduct research and establishing a “Postdoc-in-STEM” network that will connect postdocs from underrepresented groups and refine academic skills to foster representation and collaboration in the biological sciences. 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.