April
15,
2022
Biosynthesis and Mode of Action of Natural Product Antibiotics
(Drug ACTION Specific Seminar)
Bacteria produce many small molecules that possess unique structures and potent antimicrobial activity. It is often unclear how these molecules impart their activity. I will discuss our work on understanding the mode of action for the broad-spectrum, dithiolopyrrolone antibiotics. We showed that this family of natural products inhibits metal-dependent enzymes in cells via metal-ion chelation. The cyclic ene-disulfide of the dithiolopyrrolone exhibits unusual redox chemistry and is essential for activity. I will also describe our recent efforts on elucidating the mode of action of the natural product thiomarinol A, a hybrid antibiotic that combines the dithiolopyrrolone and a close analog of mupirocin, the latter of which is used to treat methicillin-resistant Staphylococcus aureus. Thiomarinol A remains effective against high-level mupirocin-resistant S. aureus. Our findings could help discover and design antibiotics that can avoid or overcome resistance.
Hosted by Jason Peters
