Biotransformations of anthracyclinones inStreptomyces coeruleorubidus andStreptomyces galilaeus

Abstract

The ability to transform biologically exogenous daunomycinone, 13-dihydrodaunomycinone, aklavinone, 7-deoxyaklavinone, ε-rhodomycinone, ε-isorhodomycinone and ε-pyrromycinone was studied in submerged cultures of the following strains: wildStreptomyces coeruleorubidus JA 10092 (W₁) and its improved variants 39–146 and 84–17 (type P₁) producing glycosides of daunomycinone and of 13-dihydro-daunomycinone, together with ε-rhodomycinone, 13-dihydrodaunomycinone and 7-deoxy-13-dihydro-daunomycinone; in five mutant types ofS. coeruleorubidus (A, B, C, D, E) blocked in the biosynthesis of glycosides and differing in the production of free anthracyclinones; in the wildStreptomyces galilaeus JA 3043 (W₂) and its improved variant G-167 (P₂) producing glycosides of ε-pyrromycinone and of aklavinone together with 7-deoxy and bisanhydro derivatives of both aglycones; in two mutant typesS. galilaeus (F and G) blocked in biosynthesis of glycosides and differing in the occurrence of anthracyclinones. The following bioconversions were observed: daunomycinone → 13-dihydrodaunomycinone and 7-deoxy-13-di-hydrodaunomycinone (all strains); 13-dihydrodaunomycinone → 7-deoxy-13-dihydrodaunomycinone (all strains); daunomyeinone or 13-dihydrodaunomycinone → glycosides of daunomyeinone and of 13-dihydrodaunomycinone, identical with metabolites W₁ and P₁ (type A), or only a single glycoside of daunomyeinone (type E); aklavinone → ε-rhodomycinone (types A and B); aklavinone → 7-deoxyaklavinone and bisan-hydroaklavinone (type C); ε-rhodomycinone → ζ-rhodomycinone (types C, E); ε-rhodomycinone → glycosides of ε-rhodomycinone (types W₂, P₂); ε-isorhodomycinone → glycosides of ε-isorhodomycinone (types W₂, P₂); ε-pyrromycinone → a glycoside of ε-pyrromycinone (types W₁, P₁). 7-Deoxyaklavinone remained intact in all tests. Exogenous daunomyeinone suppressed the biosynthesis of its own glycosidea in W₁ and P₁; it simultaneously increased the production of ε-rhodomyeinone in P₁.