Novel design of simplified β-hairpin antimicrobial peptide as a potential food preservative based on Trp-pocket backbone.

Food contamination from microbial deterioration requires the development of potent antimicrobial peptides (AMPs). The deployment of approved AMPs as dietary preservatives is limited due to barriers such as instability, toxicity, and high synthetic costs. This exploration utilizes the primary structural elements of the Trp-pocket backbone to engineer a series of β-hairpin AMPs (XWRWRPGXKXXR-NH 2 , X representing I, V, F, and/or L). Peptides WpLF, with Phe as X and Leu arranged at the 11th position, demonstrated exceptional selectivity index (SI = 123.08) and sterilization effects both in vitro and in vivo. WpLF consistently exhibited stable bacteriostasis, regardless of physiological salts, serum, and extreme pH. Mechanistic analysis indicated that the peptide penetrates microbial cell membranes, inducing membrane disruption, thereby impeding drug resistance evolution. Conclusively, AMPs engineered by the Trp-pocket skeleton hold substantial potential as innovative biological preservatives in food preservation, providing valuable insights for sustainable and safe peptide-based food preservatives. [Display omitted] • Trp-pocket backbone is successfully applied in β-hairpin antimicrobial peptides. • Optimal WpLF exhibits broad-spectrum bacteriostasis and superb biocompatibility. • WpLF targets microbial membrane integrity thus impeding drug resistance evolution. • WpLF proves stable efficacy in physiological barriers and peritonitis-sepsis model. • WpLF offers potential as a food preservative by suppressing bacterial proliferation. [ABSTRACT FROM AUTHOR]