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-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-O-L-rhodosaminyl-4-O-methyl-epsilon-rhodomycinone (4-O-methylepelmycin D). However, the attempts on production of hybrid 4-O-methylaclarubicin and 4-O-methyl-1-deoxyobelmycin by the transformants of aclarubicin and 1-deoxyobelmycin producers with pMK 100 were unsuccessful.
Miyamoto
Y
Y
Faculty of Applied Biological Science, Hiroshima University, Higashi-Hiroshima, Japan.
Ohta
S
S
Johdo
O
O
Nagamatsu
Y
Y
Yoshimoto
A
A
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005818:Genetic Engineering / Q000379:methods; D007939:Leukemia L1210; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C416821:4-O-methylepelmycin D; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; C071803:epelmycin D; D008780:Methyltransferases; C081621:carminomycin 4-O-methyltransferase