Lipidated variants of the antimicrobial peptide nisin produced via incorporation of methionine analogs for click chemistry show improved bioactivity.

ABSTRACT: The increase in antibiotic resistance calls for accelerated molecular engineering strategies to diversify natural products for drug discovery. The incorporation of non-canonical amino acids (ncAAs) is an elegant strategy for this purpose, offering a diverse pool of building blocks to introduce desired properties into antimicrobial lanthipeptides. We here report an expression system using Lactococcus lactis as a host for non-canonical amino acid incorporation with high efficiency and yield. We show that incorporating the more hydrophobic analog ethionine (instead of methionine) into nisin improves its bioactivity against several Gram-positive strains we tested. New-to-nature variants were further created by click chemistry. By azidohomoalanine (Aha) incorporation and subsequent click chemis

SUBMITTER: Guo L 

PROVIDER: S-EPMC10404616 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature