UCN-01 and UCN-02, new selective inhibitors of protein kinase C. I. Screening, producing organism and fermentation

J Antibiot (Tokyo). 1989 Apr;42(4):564-70. doi: 10.7164/antibiotics.42.564.

Abstract

In the course of continued screening program for new selective inhibitors of protein kinase C (PKC), fermentation broths from over 5,000 soil isolates were screened for their inhibitory activity of PKC. HPLC analysis of active cultures revealed that five different strains (N-71, N-115, N-126, N-128 and N-139) of Streptomyces isolated from various local soil samples were found to produce staurosporine and related compounds. Of these strains, N-126, a high producing strain, was found to produce new selective inhibitors of PKC, UCN-01 and its stereoisomer, UCN-02. The pH control of fermentation resulted in an increase of the production of UCN-01 and UCN-02.

Publication types

  • Comparative Study

MeSH terms

  • Alkaloids / biosynthesis*
  • Cell Wall / analysis
  • Chromatography, High Pressure Liquid
  • Culture Media
  • Fermentation
  • Hydrogen-Ion Concentration
  • Isomerism
  • Microscopy, Electron, Scanning
  • Protein Kinase C / antagonists & inhibitors*
  • Soil Microbiology*
  • Staurosporine
  • Streptomyces / classification
  • Streptomyces / growth & development
  • Streptomyces / metabolism*
  • Streptomyces / ultrastructure

Substances

  • Alkaloids
  • Culture Media
  • 7-hydroxystaurosporine
  • Protein Kinase C
  • Staurosporine