Start: October 1, 2026 3:30 p.m.
End: October 1, 2026 4:30 p.m.
Modifications of Pseudomonas aeruginosa Quorum Sensing Molecules Installed by Cytochrome P450 168A1
Dr. Justin Miller
Assistant Professor of Biochemistry, Department of Chemistry and Physics, Indiana State University
Thursday, 10/01 @ 3:30 PM
FB 253
The bacterium Pseudomonas aeruginosa can colonize an array of environments such as soil, plants, and animals. This prolific reach is due in large part to the adaptability conferred by its cell-to-cell communication systems. These systems (commonly called quorum sensing) use small molecule lipids produced in one bacterium to signal other bacteria nearby and solicit concerted responses to various stressors. Noting that a lipid-metabolizing cytochrome P450 (CYP168A1) is expressed as P. aeruginosa adapts to new environments, the structural similarity of the demonstrated substrates for CYP168A1 and several quorum sensing molecules used by Pseudomonas implicated this P450 as a modulator of these signaling molecules. After recombinant expression and purification of CYP168A1 in E. coli, in vitro binding and turnover assays with this P450 and these quorum sensing molecules has shown that only some of these molecules are modified by the enzyme. Indeed, the longer chained N-2-oxododecanoyl-L-homoserinelactone and not the shorter chained N-butyryl- or N-hexanoyl homoserine lactones yielded a monohydroxylated product when reactions were driven by two different cosubstrate systems. This P450 also appears to modify the heptyl- and nonyl- 3-hydroxy-4-quinolones known as the Pseudomonas quinolone signal (PQS), albeit with far less product than for the homoserine lactone. Applying LC coupled to high resolution, tandem mass spectrometry, CYP168A1 appeared to produce an ω-4 hydroxylation on N-2-oxododecanoyl-L-homoserinelactone—a product with unknown biological effects. More recent work has shown that CYP168A1 similarly modifies C8-C14 N-acyl homoserine lactones. These analytical methods will become the basis for detecting if these modified quorum sensing molecules are present in biological systems and from there beginning to establish how they influence Pseudomonas and other organisms.