CELEBRATING OUR STUDENT SUCCESS - From Genome to Antibiotic: A Nature-Inspired Approach to Drug Discovery

ABSTRACT

The rise of antibiotic resistance has created an ongoing need for new therapeutics with novel mechanisms of action to treat drug-resistant infections. Although bacterial natural products have inspired the majority of currently used antibiotics, traditional discovery methods have largely stalled, motivating the development of new strategies for identifying structurally diverse antibacterial compounds. Traditional natural product discovery relies on microbial cultivation to access the compounds encoded by biosynthetic gene clusters (BGCs). However, because many BGCs remain silent under laboratory conditions, much of this biosynthetic diversity remains inaccessible. In this seminar, I will discuss efforts to discover and develop nature-inspired antibiotics using a synthetic Bioinformatic Natural Product (synBNP) approach. By combining bioinformatic prediction of natural product structures with chemical synthesis, the synBNP approach enables exploration of the previously inaccessible chemical diversity encoded in nature without relying on microbial cultivation. This platform can be applied across multiple stages of antibiotic development, from the discovery of new antibacterial compounds to their optimization and advancement toward preclinical evaluation. These efforts highlight both the opportunities and challenges of translating bioinformatic predictions into promising therapeutic candidates.

BIOGRAPHY

Kaylyn Spotton is a Ph.D. candidate in the Tri-Institutional Ph.D. Program in Chemical Biology (TPCB), a joint program of Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and The Rockefeller University. She received her B.S. with highest honors and M.S. in Chemical Biology from Stevens Institute of Technology in 2022. As an undergraduate and master's student, Kaylyn conducted research in the laboratory of Dr. Abhishek Sharma, where she worked on developing synthetic methodologies to access novel organoboron compounds.

Kaylyn is conducting her doctoral research in the Laboratory of Genetically Encoded Small Molecules at The Rockefeller University under the mentorship of Dr. Sean F. Brady. Her research focuses on the discovery and development of nature-inspired antibiotics that evade antimicrobial resistance development by harnessing the untapped biosynthetic diversity encoded in microbial genomes. Kaylyn has been supported by the NIH T32 training grant and has received funding through the Kellen Women's Entrepreneurship Fund and the Black Family Therapeutic Development Fund to advance the preclinical development of promising novel antibiotics.