Session: Undergraduate Research Posters: Biochemistry:

Antibiotic resistance poses a continuing threat to global health as microbes adopt defenses against conventional β-lactam based therapies, often in the expression of β-lactamase enzymes. Large molecule drugs such as obafluorin, oxazolomycin, and curromycin feature the β-lactone functional group and have been successfully employed as antibiotics but are challenging to synthesize or isolate from natural sources.

Synthesized easily from a ketene heterodimer, a novel, small molecule β-lactone, (3S,4Z)-4-[1-(4-chlorophenyl)ethylidene]-3-methyloxetan-2-one) shows antimicrobial activity against Gram-positive M. luteus, Gram-negative E. coli K-12, and the fungus S. cerevisiae in disk diffusion assays. Minimum inhibitory concentrations were determined for all three microbes and UV absorption spectroscopy was used determined the binding affinity of the compound to calf thymus DNA and bovine serum albumin to characterize interactions with biomolecules. While the mechanism of action remains unknown, a sorbitol protection assay suggests that in the case of S. cerevisiae the compound is active against the cell wall.

The intermediate intensity of action of the easily synthesized small molecule support further investigation toward identifying a mechanism of action and consideration of incorporating the β-lactone moiety into future antimicrobial agents.

Dr. Michael V Coote

Saginaw Valley State University

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