Phylogeny-Informed Synthetic Biology Reveals Unprecedented Structural Novelty in Type V Glycopeptide Antibiotics

The rise and dissemination of glycopeptide antibiotic (GPA)-resistant pathogens in healthcare settings fuel efforts to discover GPAs that can overcome resistance. Members of the type V subclass of GPAs can evade common GPA resistance mechanisms and offer promise as new drug leads. We characterize five new type V GPAs-rimomycin-A/B/C and misaugamycin-A/B-discovered through a phylogeny-guided genome mining strategy coupled with heterologous …