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

Abstract

Transformation of Streptomyces galilaeus ATCC 31133 with the aklavinone 11-hydroxylase gene (dnr F) 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.