Dehydroalanine (Dha) and dehydrobutyrine (Dhb) display considerable flexibility in a variety of chemical and biological reactions. Natural products containing Dha and/or Dhb residues are often found to possess diverse biological activities. While the ( Z )‐geometry is predominant in nature, only a handful of metabolites containing ( E )‐Dhb have been found thus far. Here we report discovery of a new antimicrobial peptide, albopeptide, through NMR analysis and chemical synthesis, which contains two contiguous unsaturated residues, Dha‐( E )‐Dhb. It displays narrow‐spectrum activity against vancomycin‐resistant Enterococcus faecium. In vitro biochemical assays show that albopeptide originates from a noncanonical NRPS pathway, featured with dehydration processes, catalysed by unusual condensation domains. Finally, we provide evidence of the occurrence of a previously untapped group of short unsaturated peptides in the bacterial kingdom, suggesting an important biological function in bacteria.
- natural product discovery
- peptide synthesis
- nonribosomal peptide synthetases
- dehydroamino acids
- in vitro pathway reconstitution