Salamandamide Lipodipeptides Are Biosynthetic Intermediate Shunt Products of the Nonamodular Nonribosomal Peptide Assembly Lines of the Viscosin Family.

Chemical investigation of a salamander-mucus-associated strain led to the isolation and chemical characterization of salamandamide A, a new lipo-dipeptide, along with known lipopeptides of the pseudodesmin and tolaasin class. Genome mining revealed that no specific gene cluster codes for the biosynthesis of salamandamide A. Stereochemical analyses and mutagenesis experiments linked the biosynthesis of the lipo-dipeptide salamandamide A to the NRPS gene cluster of the lipo-nonapeptide pseudodesmin. Further chemical investigations showed that this finding appears to be a broader concept and that all nonamodular NRPS gene clusters of the viscosin family were capable to produce, beside the expected lipo-nonapeptide, the corresponding lipo-dipeptide as a shunt product which also led to the discovery of salamandamide B from SS101.