Identification of pulvomycin as an inhibitor of the futalosine pathway

J Antibiot (Tokyo). 2021 Nov;74(11):825-829. doi: 10.1038/s41429-021-00465-8. Epub 2021 Aug 20.

Abstract

Menaquinone is an essential cofactor in the electron-transfer pathway for bacteria. Menaquinone is biosynthesized from chorismate using either the well-known canonical pathway established by pioneering studies in model microorganisms or the futalosine pathway, which we discovered in Streptomyces. Because Helicobacter pylori, which causes stomach cancer, uses the futalosine pathway and most beneficial intestinal bacteria including lactobacilli use the canonical pathway, the futalosine pathway will be a great target to develop antibiotics specific for H. pylori. Here, we searched for such compounds from metabolites produced by actinomycetes and identified pulvomycin from culture broth of Streptomyces sp. K18-0194 as a specific inhibitor of the futalosine pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / chemistry
  • Aminoglycosides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Culture Media / chemistry
  • Helicobacter pylori / drug effects
  • Nucleosides / drug effects*
  • Nucleosides / metabolism
  • Signal Transduction / drug effects
  • Streptomyces / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Culture Media
  • Nucleosides
  • futalosine
  • pulvomycin