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Victoria Meadows

Posted on October 12, 2022


Date - October 12, 2022
1:00 pm - 2:00 pm


Public PhD Defense
Department of Chemistry & Biochemistry
UNC Greensboro
Reddick Research Laboratory
Title: Investigating the cytochrome P450 enzyme (PksS) from Bacillus species in the biosynthesis of bacillaene


Bacterial secondary metabolites from Bacillus species have an important role in drug discovery and development. This dissertation focuses on research to characterize enzymes and biosynthetic pathways from Bacillus subtilis and Bacillus amyloliquefaciens. We have studied the biosynthetic pathway of the polyketide bacillaene from the trans-acyltransferase polyketide synthase system from Bacillus subtilis and Bacillus amyloliquefaciens. The biosynthetic pathway of bacillaene has several interesting features, including β-branching, a trans-enoylreductase, and a cytochrome P450 enzyme (PksS), making this a worthwhile system to study. The immediate product of the polyketide synthase from this pathway, dihydrobacillaene, is hypothesized to be oxidized by an unknown process to produce bacillaene. Previous research from our lab has shown that the cytochrome P450 enzyme, PksS, will react with dihydrobacillaene, although the product of that reaction is still unknown. The goal of the research described in this presentation is to determine that product.  To characterize this reaction, we have improved ultra-pressure liquid chromatography (UPLC) methodologies to detect the product of the reaction between dihydrobacillaene and the PksS enzyme. To simplify the complex mixtures of the unstable natural products needed for these studies, we will use knockout mutants of B. subtilis and B. amyloliquefaciens that lack pksS/baeS to determine the product of the reaction between the knockout mutations and the cytochrome P450 enzyme, PksS.


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