ABSTRACT
The noursamycins A-F are chlorinated cyclic hexapeptides, which were identified and isolated from the strain Streptomyces noursei NTR-SR4 overexpressing a LuxR-like transcriptional activator. The molecules were structurally characterized by mass spectrometric analyses and 1D and 2D NMR spectroscopic techniques. The enzymatic machinery involved in the biosynthesis of these peptides is represented by a modular nonribosomal peptide synthetase (NRPS), and the corresponding gene cluster was identified in the S. noursei genome. The latter suggested the biosynthetic pathway for the noursamycins. Spectral networking analysis uncovered noursamycin derivatives that were later found to result from a relaxed substrate specificity of the A3 and A4 adenylation domains of the NRPS. The stereochemistry of the amino acid constituents of the noursamycins was resolved by chemical derivatization, subsequent enantiomer analytics by GC-EIMS, and in silico data analyses. Noursamycins A and B exhibited antibacterial activity against Gram-positive and Gram-negative bacteria, while no apparent cytotoxicity was observed.