Generating and Screening β-Lactones Against Essential Tuberculosis Enzymes
Department
Chemistry
Advisor
Christenson, James
Document Type
Poster
Start Date
2-26-2025 3:00 PM
End Date
2-26-2025 5:00 PM
Abstract
β-lactone natural products are chemical compounds characterized by strained four-membered rings that can act as potent enzyme inhibitors. β-lactone synthetases are enzymes that utilize ATP and β-hydroxy substrates to drive intramolecular ring closure and subsequent β-lactone formation and represent an attractive route to the asymmetric synthesis of medically relevant β-lactones, particularly against tuberculosis. Research suggests that the structure of β-lactone molecules can halt the growth of Mycobacterium tuberculosis through covalent inhibition of the Pks13, preventing cell wall integrity. The focus of this project was to transform, express, and purify β-lactone synthetases to use in an assay against lipases similar to Pks13, and Pks13. Our findings suggest that β-lactones do inhibit both porcine pancreatic lipase and candida rugosa lipase, but were inconclusive about Pks13.
Recommended Citation
Stauffer, Mirah and Rudolph, Tristan, "Generating and Screening β-Lactones Against Essential Tuberculosis Enzymes" (2025). Day of Scholarship. 28.
https://spark.bethel.edu/dayofscholarship/spring2025/feb26/28
Generating and Screening β-Lactones Against Essential Tuberculosis Enzymes
β-lactone natural products are chemical compounds characterized by strained four-membered rings that can act as potent enzyme inhibitors. β-lactone synthetases are enzymes that utilize ATP and β-hydroxy substrates to drive intramolecular ring closure and subsequent β-lactone formation and represent an attractive route to the asymmetric synthesis of medically relevant β-lactones, particularly against tuberculosis. Research suggests that the structure of β-lactone molecules can halt the growth of Mycobacterium tuberculosis through covalent inhibition of the Pks13, preventing cell wall integrity. The focus of this project was to transform, express, and purify β-lactone synthetases to use in an assay against lipases similar to Pks13, and Pks13. Our findings suggest that β-lactones do inhibit both porcine pancreatic lipase and candida rugosa lipase, but were inconclusive about Pks13.
