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Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus

dc.contributor.authorPatallo, Eugenio
dc.contributor.authorBlanco Blanco, María Gloria 
dc.contributor.authorFischer, Carsten
dc.contributor.authorFernández Braña, Alfredo Javier 
dc.contributor.authorRohr, Jürgen
dc.contributor.authorMéndez Fernández, María del Carmen 
dc.contributor.authorSalas Fernández, José Antonio
dc.identifier.citationJournal of Biological Chemistry, 276, p. 18765-18774 (2001); doi:10.1074/jbc.M101225200
dc.description.abstractThe anthracycline-like polyketide drug elloramycin is produced by Streptomyces olivaceusTü2353. Elloramycin has antibacterial activity against Gram-positive bacteria and also exhibits antitumor activity. From a cosmid clone (cos16F4) containing part of the elloramycin biosynthesis gene cluster, three genes (elmMI, elmMII, andelmMIII) have been cloned. Sequence analysis and data base comparison showed that their deduced products resembledS-adenosylmethionine-dependentO-methyltransferases. The genes were individually expressed in Streptomyces albus and also coexpressed with genes involved in the biosynthesis of l-rhamnose, the 6-deoxysugar attached to the elloramycin aglycon. The resulting recombinant strains were used to biotransform three different elloramycin-type compounds: l-rhamnosyl-tetracenomycin C,l-olivosyl-tetracenomycin C, andl-oleandrosyl-tetracenomycin, which differ in their 2′-, 3′-, and 4′-substituents of the sugar moieties. When only the three methyltransferase-encoding genes elmMI, elmMII, and elmMIII were individually expressed in S. albus, the methylating activity of the three methyltransferases was also assayed in vitro using various externally added glycosylated substrates. From the combined results of all of these experiments, it is proposed that methyltransferases ElmMI, ElmMII, and ElmMIII are involved in the biosynthesis of the permethylatedl-rhamnose moiety of elloramycin. ElmMI, ElmMII, and ElmMIII are responsible for the consecutive methylation of the hydroxy groups at the 2′-, 3′-, and 4′-position, respectively, after the sugar moiety has been attached to the aglyconspa
dc.description.sponsorshipThis work was supported by European Community Grant BIO4-CT96-0068 (to J. R. and J. A. S.), Spanish Ministry of Education and Science Grant BIO97-0771 through the “Plan Nacional en Biotecnologia” (to J. A. S.), and grants from the South Carolina Commission of Higher Education as well as the United States Department of Defense (to J. R.).
dc.format.extentp. 18765-18774spa
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.relation.ispartofJournal of Biological Chemistry, 276spa
dc.rights© 2001 by The American Society for Biochemistry and Molecular Biology, Inc
dc.titleDeoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceusspa

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