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.
Bibliographical noteAcknowledgement: QF and HD are grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM (PEER/PERCE) for financial support. HD, ZL and SW thank the financial supports of Biotechnology and Biological Sciences Research Council UK (BBSRC, BB/P00380X/1) and the Royal Society-NSFC Newton Mobility Grant Award (IEC\NSFC\170617 to HD). HD, SAM and CP thank Business Interaction Vouchers (BIV009) from BBSRC funded Natural Products discovery and bioengineering Network (NPRONET). Y.G. thanks NSFC oversea scholarship, Natural Science Foundation of Jiangsu Province (BK20170450), and the Open Research fund of Jiangsu Key Laboratory of Marine Biotechnology (HS2017003).
- natural product discovery
- peptide synthesis
- nonribosomal peptide synthetases
- dehydroamino acids
- in vitro pathway reconstitution
- in-vitro pathway reconstitution