earticle

영어

Combinatorial biosynthesis is an alternative way for accessing naturally unavailable natural products or improving activity of already existing biomolecules by their modification. Biosynthesis of different deoxy-aminosugar and its attachment to the same or different anthracyclinone aglycones in vivo would lead to the formation of novel anthracycline compounds. Unlike doxorubicin, anthracyclines with N-alkylated sugar moieties were weakly mutagenic or not mutagenic at all in both bacterial and mammalian cells. Disruption of glycosyltransferase gene, dnrS, involved in the biosynthesis of the doxorubicin from Streptomyces peucetius ATCC 27952 led to accumulation of a non-glycosylated intermediate ε-rhodomycinone. Complementation experiment was carried out to introduce L-rhodosamine sugar for the production of rhodosaminyl-doxorubicin. Chromosomal integration of desVI encoding N,N-dimethyltransferase from Streptomyces venezuelae and aknS encoding glycosyltransferase along with its auxiliary gene aknT from Streptomyces galilaeus in the dnrS disruptant of S. peucetius led to formation of rhodosaminyl-doxorubicin.