Discovery and biosynthetic investigation of a new antibacterial dehydrated non‐ribosomal tripeptide

Shan Wang* (Corresponding Author), Qing Fang, Zhou Lu, Yingli Gao, Laurent Trembleau, Rainer Ebel, Jeanette H Andersen, Carol Philips, Samantha Law, Hai Deng* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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 display 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 featuring dehydration processes and 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.

Original languageEnglish
Pages (from-to)3229-3237
Number of pages9
JournalAngewandte Chemie International Edition
Volume60
Issue number6
Early online date11 Dec 2020
DOIs
Publication statusPublished - 8 Feb 2021

Keywords

  • natural product discovery
  • peptide synthesis
  • nonribosomal peptide synthetases
  • dehydroamino acids
  • in vitro pathway reconstitution
  • in-vitro pathway reconstitution

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