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Utilizing bioinformatics, biocatalysis, and synthetic chemistry to access natural products

Natural products (NPs) from the soil dwelling Actinomycetota are a bountiful source of bioactive molecules, including medicines, agricultural products, and chemical tools to study biological processes. Additionally, the biosynthetic enzymes that produce them perform unique chemistries and are excellent starting points for biocatalysts. Unfortunately, many biosynthetic gene clusters (BGCs, clusters of genes that encode for the enzymes that produce NPs) are cryptic. Accessing NPs from these cryptic BGCs is quite challenging, thus slowing the discovery of novel bioactive NPs that can serve as leads for medicines and agricultural products. Herein, we are exploring two different methods to access NPs from cryptic BGCs: 1) bioinformatics inspired direct chemical synthesis and 2) BGC induction using quorum sensing molecules. Additionally, we are discovering and utilizing the biosynthetic enzymes to access otherwise challenging to access products, with a particular focus on cyclic peptides. Overall, these approaches enable us to access molecules that are otherwise inaccessible, thus helping to expand the medicinal and agricultural pipelines.

Biography

Betsy attended Rhodes College, where she obtained her B.S. in chemistry in 2010. She conducted graduate research with Prof. Paul Hergenrother at the UIUC on the synthesis and mechanisms of the deoxynybomycin family of natural products. After obtaining her Ph.D. in 2015, she performed postdoctoral studies with Prof. William Metcalf at UIUC studying the biosynthesis of phosphonate containing natural products. Betsy started her laboratory in the Departments of Chemistry and Department of Medicinal Chemistry and Molecular Pharmacology at Purdue University in the Fall of 2018 and was promoted to associate professor in Fall 2025. In her lab, research focuses on the identification of novel bioactive peptide natural products from cryptic bacterial biosynthetic gene clusters. Additionally, she studies the unique and challenging chemistries performed by natural product biosynthetic enzymes, such as cyclization of small peptides.