Panosialins, inhibitors of enoyl-ACP reductase from Streptomyces sp. AN1761

J Microbiol Biotechnol. 2013 Feb;23(2):184-8. doi: 10.4014/jmb.1209.09038.

Abstract

In the continued search for inhibitors of enoyl-acyl carrier protein (ACP) reductase, we found that four acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761 potently inhibited bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Their structures were identified as panosialins A, B, wA, and wB by MS and NMR data. They showed stronger inhibition against S. aureus FabI and S. pneumoniae FabK with IC50 of 3-5 microM than M. tuberculosis InhA with IC50 of 9-12 microM. They also exhibited a stronger antibacterial spectrum on S. aureus and S. pneumoniae than M. tuberculosis. In addition, the higher inhibitory activity of panosialin wB than panosialin B on fatty acid biosynthesis was consistent with that on bacterial growth, suggesting that they could exert their antibacterial activity by inhibiting fatty acid synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / isolation & purification
  • Benzene Derivatives / pharmacology*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acids / metabolism
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Metabolic Networks and Pathways / drug effects
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / growth & development
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / growth & development
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / enzymology
  • Streptococcus pneumoniae / growth & development
  • Streptomyces / chemistry*

Substances

  • Bacterial Proteins
  • Benzene Derivatives
  • Enzyme Inhibitors
  • Fatty Acids
  • panosialin
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)