New anthracycline metabolites produced by the aklavinone 11-hydroxylase gene in Streptomyces galilaeus ATCC 31133

J Antibiot (Tokyo). 1996 Apr;49(4):355-60. doi: 10.7164/antibiotics.49.355.

Abstract

Transformation of Streptomyces galilaeus ATCC 31133 with the aklavinone 11-hydroxylase gene (dnrF) resulted in the production of many red pigments. The new metabolites were purified and their structures were determined as 11-hydroxylated aclacinomycin A, B and T by spectral analysis. This result indicated that the dnrF was stably expressed in the strain S. galilaeus ATCC 31133 to give rise to hybrid aclacinomycins. In addition, a new aclacinomycin analog named 11-hydroxyaclacinomycin X was isolated from the same culture. Its structure was elucidated as 2"'-amino-11-hydroxyaclacinomycin Y. It showed strong cytotoxicity against several human tumor cell lines, especially leukemia and melanoma cell lines.

MeSH terms

  • Aclarubicin / analogs & derivatives*
  • Aclarubicin / chemistry
  • Aclarubicin / metabolism
  • Aclarubicin / pharmacology
  • Anthracyclines / metabolism*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Drug Screening Assays, Antitumor
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Structure
  • Streptomyces / enzymology
  • Streptomyces / genetics*
  • Streptomyces / metabolism

Substances

  • 11-hydroxyaclacinomycin X
  • Anthracyclines
  • Antineoplastic Agents
  • aclacinomycins
  • Aclarubicin
  • aklavinone 11-hydroxylase
  • Aryl Hydrocarbon Hydroxylases