Enzymatic Cascade To Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Org Lett. 2019 Nov 1;21(21):8635-8640. doi: 10.1021/acs.orglett.9b03245. Epub 2019 Oct 11.

Abstract

Natural products are the greatest source of antimicrobial agents, although their structural complexity often renders synthetic production and diversification of key classes impractical. One pertinent example is the glycopeptide antibiotics (GPAs), which are highly challenging to synthesize due to their heavily cross-linked structures. Here, we report an optimized method that generates >75% tricyclic peptides from synthetic precursors in order to explore the acceptance of novel GPA precursor peptides by these key existent biosynthetic enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry*
  • Cyclization
  • Glycopeptides / biosynthesis*
  • Glycopeptides / chemistry*

Substances

  • Anti-Bacterial Agents
  • Glycopeptides