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

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 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.
Original languageEnglish
JournalAngewandte Chemie International Edition
Early online date27 Oct 2020
DOIs
Publication statusE-pub ahead of print - 27 Oct 2020

Keywords

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

Fingerprint Dive into the research topics of 'Discovery and biosynthetic investigation of a new antibacterial dehydrated non‐ribosomal tripeptide'. Together they form a unique fingerprint.

Cite this