Guided by cell-wall specific biological assays, our search for antibacterial agents from natural sources resulted in the discovery of the muraymycins, a family of novel nucleoside-lipopeptide antibiotics with a unique core structure. The muraymycins are cell wall biosynthesis inhibitors with in vitro activity and in vivo efficacy. The compounds show antimicrobial activity against Gram-positive bacteria and excellent activity against a permeable E. coli strain. The muraymycins were shown to inhibit MraY, an enzyme that links UDP-MurNAc-pentapeptide to the C55 lipid carrier during bacterial cell-wall biosynthesis. We report here the structures of the muraymycin family of peptidoglycan biosynthesis inhibitors from a Streptomyces sp. organism.