Biosynthesis of the Antibiotic Nematophin and Its Elongated Derivatives in Entomopathogenic Bacteria

Org Lett. 2017 Feb 17;19(4):806-809. doi: 10.1021/acs.orglett.6b03796. Epub 2017 Jan 30.

Abstract

Nematophin, a known antibiotic natural product against Staphylococcus aureus for almost 20 years, is produced by all strains of Xenorhabdus nematophila. Despite its simple structure, its biosynthesis was unknown. Its biosynthetic pathway is reported using heterologous production in Escherichia coli. Additionally, the identification, structure elucidation, and biosynthesis of six extended nematophin derivatives from Xenorhabdus PB62.4 carrying an additional valine are reported. Preliminary bioactivity studies suggest a biological role of these compounds in the bacteria-nematode-insect symbiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / biosynthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antiparasitic Agents / chemistry
  • Antiparasitic Agents / metabolism
  • Antiparasitic Agents / pharmacology
  • Escherichia coli / metabolism
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacology
  • Leishmania / drug effects
  • Myoblasts / drug effects
  • Myoblasts / parasitology
  • Nematoda / drug effects
  • Plasmodium falciparum / drug effects
  • Rats
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Trypanosoma / drug effects
  • Xenorhabdus / metabolism

Substances

  • Anti-Bacterial Agents
  • Antiparasitic Agents
  • Indoles
  • nematophin