Probing the Breadth of Macrolide Glycosyltransferases: In Vitro Remodeling of a Polyketide Antibiotic Creates Active Bacterial Uptake and Enhances Potency

摘要

Macrolides constitute an important group of antibiotics that target primarily Gram-positive prokaryotes and collectively have been classed as "the last line of defense" against rapidly emerging resistant pathogen strains.They comprise a macrocyclic polyketide backbone to which glycans are appended that alter activity,specificity,and resistance mechanisms.Antibiotic glycan alteration (so-called glycorandomization) is a potentially powerful strategy in combating emerging bacterial resistance.Rare,elegant examples of in vitro glycan modification of antibiotics have largely focused on cyclic nonribosomal peptides,such as vancomycin.