Chemical and biological characterization of two FK506 analogs produced by targeted gene disruption in Streptomyces sp. MA6548

J Antibiot (Tokyo). 1997 May;50(5):418-23. doi: 10.7164/antibiotics.50.418.

Abstract

Two genetically engineered mutant strains of Streptomyces sp. MA6548 produced two FK506 analogs, 9-deoxo-31-O-demethylFK506 and 31-O-demethylFK506. The structures were determined by a combination of NMR and mass spectrometry. These compounds exhibited immunosuppressive and antifungal activities, albeit reduced, compared to FK506. Both compounds contain a free hydroxyl group at C-31 for the synthesis of novel FK506 derivatives.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology
  • Aspergillus niger / drug effects
  • Chromatography, High Pressure Liquid
  • Fermentation
  • Genetic Engineering / methods
  • Immunosuppressive Agents / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Streptomyces / genetics
  • Streptomyces / metabolism
  • Tacrolimus / analogs & derivatives*
  • Tacrolimus / chemistry
  • Tacrolimus / pharmacology

Substances

  • 9-deoxo-31-O-demethyl-FK506
  • Antifungal Agents
  • Immunosuppressive Agents
  • 31-O-demethyl-FK506
  • Tacrolimus