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

The Journal of Antibiotics
2000.0

Abstract

A new hybrid anthracycline antibiotic was produced by heterologous expression of dnrK encoding carminomycin 4-0-metyltransferase in an epelmycin-producing Streptomyces violaceus. pMKlOOwas constructed by insertion of Steptomyces peucetius dnrK gene in Steptomyces-expression 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 7-0-L-rhodosaminyl-4-0-methyl-£-rhodomycinone (4-0 methylepelmycin D). However, the attempts on production of hybrid 4-0-methylaclarubicin and 4-0-methyl-l-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMKlOOwere unsuccessful.

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