Discovery of okilactomycin and congeners from Streptomyces scabrisporus by antisense differential sensitivity assay targeting ribosomal protein S4

J Antibiot (Tokyo). 2009 Feb;62(2):55-61. doi: 10.1038/ja.2008.8. Epub 2009 Jan 9.


Protein synthesis inhibition is a highly successful target for developing clinically effective and safe antibiotics. There are several targets within the ribosomal machinery, and small ribosomal protein S4 (RPSD) is one of the newer targets. Screening of microbial extracts using antisense-sensitized rpsD Staphylococcus aureus strain led to isolation of okilactomycin and four new congeners from Streptomyces scabrisporus. The major compound, okilactomycin, was the most active, with a minimum detection concentration of 3-12 microg ml(-1) against antisense assay, and showed an MIC of 4-16 microg ml(-1) against Gram-positive bacteria, including S. aureus. The congeners were significantly less active in all assays, and all compounds showed a slight preferential inhibition of RNA synthesis over DNA and protein synthesis. Antisense technology, due to increased sensitivity, continues to yield new, even though weakly active, antibiotics.

MeSH terms

  • Bacteria / drug effects
  • Chromatography, High Pressure Liquid
  • Fermentation
  • Gram-Positive Bacteria / drug effects
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Oligonucleotides, Antisense / pharmacology*
  • Phylogeny
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Ribosomal, 16S / biosynthesis
  • RNA, Ribosomal, 16S / genetics
  • Ribosomal Proteins / drug effects*
  • Ribosomal Proteins / genetics*
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / metabolism
  • Streptomyces / classification
  • Streptomyces / genetics*
  • Streptomyces / metabolism*


  • Lactones
  • Nucleic Acid Synthesis Inhibitors
  • Oligonucleotides, Antisense
  • Protein Synthesis Inhibitors
  • RNA, Ribosomal, 16S
  • Ribosomal Proteins
  • ribosomal protein S4
  • okilactomycin