RESUMO
Glycosylation pattern in cosmomycins is a distinctive feature among anthracyclines. These antitumor compounds possess two trisaccharide chains attached at C-7 and C-10, each of them with structural variability, mainly at the distal deoxysugar moieties. We have characterized a 14-kb chromosomal region from Streptomyces olindensis containing 13 genes involved in cosmomycin biosynthesis. Two of the genes, cosG and cosK, coding for glycosyltransferase were inactivated with the generation of five new derivatives. Structural elucidation of these compounds showed altered glycosylation patterns indicating the capability of both glycosyltransferases of transferring deoxysugars to both sides of the aglycone and the flexibility of CosK with respect to the deoxysugar donor. A model is proposed for the glycosylation steps during cosmomycins biosynthesis.
Assuntos
Antraciclinas/química , Antraciclinas/metabolismo , Glicosiltransferases/genética , Streptomyces/metabolismo , Proteínas de Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Deleção de Genes , Ordem dos Genes , Teste de Complementação Genética , Glicosilação , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Estrutura Molecular , Análise de Sequência de DNA , Streptomyces/enzimologia , Streptomyces/genéticaRESUMO
Cosmomycin D (CosD) is the major constituent fraction isolated from a culture of Streptomyces olindensis ICB20. The ability of this compound to intercalate with double-stranded DNA was studied by gel mobility shift assays and electrospray ionization mass spectrometry (ESI-MS). ESI-MS experiments showed that the complex of CosD with 16-mer double-stranded DNA was at least as stable as a complex of daunorubicin with the same DNA sequence. This is the first study showing DNA binding properties of an anthracycline containing a beta-rhodomycinone aglycone chromophore O-linked to two trisaccharide chains.