Production of a New Hybrid Anthracycline 4-O-Methylepelmycin by Heterologous Expression of dnrK in Epelmycin-producing Streptomyces violaceus

A new hybrid anthracycline antibiotic was produced by heterologous expression of dnrK encoding carminomycin 4-O-metyltransferase in an epelmycin-producing Streptomyces violaceus. pMK100 was constructed by insertion of Steptomyces peucetius dnrK gene in Steptomyces-expresion vector pIJ6021 and introduced to the epelmycin producer. The transformant produced a hybrid anthracycline antibiotic together with host epelmycins when cultured in antibiotic production medium in the presence of thiostrepton. The hybrid anthracycline was determined to be 7-O-L-rhodosaminyl-4-O-methyl-e-rhodomycinone (4-O-memylepelmycin D). However, the attempts on production of hybrid 4-O-methyl aclarubicin and 4-O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMK100 were unsuccessful.