Rational design of a sulfonium-stabilized cyclic temporin-SHf as a potential food preservative.

Food safety is increasingly threatened by contamination with foodborne pathogenic microorganisms, particularly in the context of escalating antimicrobial resistance. Natural antimicrobial peptides, such as temporin-SHf, are considered promising candidates for food preservation; however, their practical application is often limited by poor stability and insufficient antimicrobial efficacy. Herein, a sulfonium-stabilized cyclization strategy was employed to improve the stability and antimicrobial activity of temporin-SHf. By conformationally constraining the peptide, its resistance to serum proteases, pH fluctuations, and saline environments was significantly enhanced. Moreover, the incorporation of sulfonium moieties increased peptide cationicity, thereby reinforcing electrostatic interactions with bacterial cell membranes and resulting in an approximately ten-fold increase in antimicrobial potency relative to the native peptide. Furthermore, TP [4,7]-Ph showed improved antimicrobial activity against selected foodborne bacterial strains and exhibited synergistic effects with several conventional food preservatives. In an S. aureus-inoculated pork model, TP [4,7]-Ph treatment reduced bacterial growth and helped maintain pork quality, as reflected by lower drip loss and delayed physicochemical deterioration. Overall, these findings support the potential of sulfonium-stabilized cyclic temporin-SHf peptides as candidates for food preservatives, while further validation against additional foodborne pathogens in relevant food matrices remains necessary.