Research and insights on antimicrobial peptides derived from fermented yak milk casein based on enzymatic cleavage sites and molecular interactions

The present study characterized a novel antimicrobial peptide (AMP) identified from the hydrolysates of fermented yak milk proteins. In total, 469 peptide fragments were identified. Enzymatic cleavage site analysis indicated that the AMPs were predominantly enriched in α s1 -casein. A novel AMP, namely, FYMp9 was identified, and it exhibited significant antibacterial activity against Staphylococcus aureus (half maximal inhibitory concentration [IC 50 ] value of 0.32 mg/mL) and demonstrated good biosafety. FYMp9 irreversibly damaged S. aureus cells by disrupting the bacterial cell membrane structure. Molecular docking analysis revealed that FYMp9 bound to specific amino acid residues of DnaK and histidine kinase accessory gene regulator C (AgrC), forming stable complexes and exerting synergistic antibacterial effects via a dual mechanism. The present study revealed the release pattern of AMPs in fermented milk proteins, providing a theoretical foundation for the molecular design of novel antimicrobial agents and offering new insights into addressing global food safety and antimicrobial resistance challenges.