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Discovery and Biosynthetic Investigation of a New Antibacterial Dehydrated Non‐Ribosomal Tripeptide
Author(s) -
Wang Shan,
Fang Qing,
Lu Zhou,
Gao Yingli,
Trembleau Laurent,
Ebel Rainer,
Andersen Jeanette H.,
Philips Carol,
Law Samantha,
Deng Hai
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202012902
Subject(s) - tripeptide , chemistry , dehydroalanine , enterococcus faecium , antimicrobial , bacteria , biochemistry , peptide , stereochemistry , cyclic peptide , combinatorial chemistry , organic chemistry , biology , antibiotics , genetics
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.