Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of molecular diversity and utility

Angew Chem Int Ed Engl. 2013 Nov 18;52(47):12308-12. doi: 10.1002/anie.201305569. Epub 2013 Oct 2.

Abstract

Diversity-oriented biosynthesis of a library of antimycin-like compounds (380 altogether) was accomplished by using multiplex combinatorial biosynthesis. The core strategy depends on the use of combinatorial chemistry at different biosynthetic stages. This approach is applicable for the diversification of polyketides, nonribosomal peptides, and the hybrids that share a similar biosynthetic logic.

Keywords: antimycins; biosynthesis; combinatorial chemistry; dilactones; natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Animals
  • Antimycin A / analogs & derivatives*
  • Antimycin A / biosynthesis
  • Antimycin A / pharmacology
  • Antimycin A / toxicity
  • Candida albicans / drug effects
  • Catalysis
  • Cell Line
  • Cell Survival / drug effects
  • Combinatorial Chemistry Techniques*
  • Copper / chemistry
  • Genetic Variation*
  • Lactones / chemistry
  • Mice
  • Peptides / chemistry
  • Peptides / metabolism
  • Polyketides / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / toxicity

Substances

  • Lactones
  • Peptides
  • Polyketides
  • Small Molecule Libraries
  • antimycin
  • Antimycin A
  • Copper