Recombinant Microorganisms for the Biosynthesis of Glycosylated Antitumor Compounds

Actinomycetes produce many bioactive compounds with clinical, veterinary, or agricultural applications. Many of these natural products contain sugars attached to the corresponding agly-cons, which usually participate in the molecular recognition of the cellular target. The glycosy-lation pattern of these complex metabolites can be altered by chemical synthesis or synthetic modification of intermediates usually produced via fermentation and by the use of genetically engineered recombinant microorganisms and biosynthetic genes for in vivo experiments through combinatorial biosynthesis. Here, we describe procedures to generate novel glycosylated compounds derived from the antitumor compound elloramycin. This procedure involves biotransfor-mation of different recombinant strains of Streptomyces albus harboring the elloramycin ElmGT glycosyltransferase and able to synthesize different dTDP-activated deoxysugars whose biosynthesis is directed by different plasmids.