New antibiotics are desperately needed to treat antibiotic-resistant infections. Antibioticresistant bacteria cause more than 2.8 million illnesses and 35,000 deaths in the United States each year. Gram-positive pathogens -including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), antibiotic-resistant Streptococcus pneumoniae, and three others -cause more than 54% of these illnesses and 60% of these deaths. Clovibactin has recently been reported as a promising antibiotic against Gram-positive bacteria, including drug-resistant human pathogens such as MRSA and VRE, without detectable resistance. Clovibactin is a cyclodepsipeptide composed of eight amino acids (Figure ). Residues 1-4 comprise a linear tail and residues 5-8 comprise a macrocycle. The most notable feature of clovibactin is the rare, non-canonical amino acid D-hydroxyasparagine (D-Hyn) at position five, which serves as the linchpin in the macrolactone ring.