Genome-Led\nDiscovery of the Antibacterial Cyclic Lipopeptide\nKutzneridine A and Its Silent Biosynthetic Gene Cluster from <i>Kutzneria</i> Species

Genome analysis of <i>Kutzneria</i> sp. CA-103260\nrevealed\na putative lipopeptide-encoding biosynthetic gene cluster (BGC) that\nwas cloned into a bacterial artificial chromosome (BAC) and heterologously\nexpressed in <i>Streptomyces coelicolor</i> M1152. As a\nresult, a novel cyclic lipo-tetrapeptide containing two diaminopropionic\nacid residues and an exotic <i>N</i>,<i>N</i>-acetonide\nring, kutzneridine A (<b>1</b>), was isolated and structurally\ncharacterized. Evaluation of the extraction conditions and isotope-labeling\nchemical modifications showed that the acetonide ring originated from\nacetone during isolation. The BGC was analyzed <i>in silico</i> and a biosynthetic pathway to <b>1</b> was proposed. Kutzneridine\nA displayed remarkable antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococci</i>.