Antimicrobial agents with favourable food safety profiles are urgently needed to control human pathogenic bacteria associated with aquatic products. A mass spectrometry- and bioassay-guided screening approach was employed to identify structurally novel peptide natural products with potential as food-safe antimicrobial agents. This effort led to the discovery of eight new antibacterial 11-mer peptaibols, sesquicilins A–H ( 1 – 8 ), from the ascomycete fungus Sesquicilium sp. QL0466. Their planar structures were elucidated by integrated analysis of HRESIMS/MS and NMR spectroscopic data, and the absolute configurations of the chiral amino acids were established using the advanced Marfey's method. These compounds feature characteristic Ser 2 and Iva 8 -Gln 9 -Aib/Iva/Leu 10 motifs, setting them apart from previously reported 11-mer peptaibols. Bioinformatic analysis revealed a nonribosomal peptide synthetase gene cluster likely responsible for sesquicilin biosynthesis. Among these peptaibols, compound 2 potently inhibited the growth of Staphylococcus and Salmonella species, while showing no detectable activity against common aquaculture pathogenic bacteria. This selective antibacterial profile minimizes the risk of misuse in aquaculture and the consequent rapid emergence of antimicrobial resistance. Structure-activity relationship analysis indicated the critical role of d -isovaline residue at the 1st position in mediating antibacterial activity.
Song et al. (2026) studied this question.