title: Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus.
abstract: The glycopeptide teicoplanin is used for the treatment of serious infections caused by Gram-positive pathogens. The tcp gene cluster, devoted to teicoplanin biosynthesis in the actinomycete Actinoplanes teichomyceticus, was isolated and characterized. From sequence analysis, the tcp cluster spans approximately 73 kb and includes 39 ORFs participating in teicoplanin biosynthesis, regulation, resistance and export. Of these, 34 ORFs find a match in at least one of the five glycopeptide gene clusters previously characterized. Putative roles could be assigned for most of the tcp genes. The two glycosyltransferases responsible for attaching amino sugars to amino acids 4 and 6 of the teicoplanin aglycon were overexpressed in Escherichia coli and characterized. They both recognize N-acetylglucosamine as the substrate. tGtfA can add a sugar residue in the presence or absence of N-acetylglucosamine at amino acid 4, while tGtfB can only glycosylate the teicoplanin aglycon.
authors.affiliation: Vicuron Pharmaceuticals, via R. Lepetit 34, 21040 Gerenzano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.affiliation: Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, 9751 NN Haren, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: Kloosterman
authors.affiliation: Vicuron Pharmaceuticals, via R. Lepetit 34, 21040 Gerenzano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, 9751 NN Haren, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: de Vreugd
authors.affiliation: Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, 9751 NN Haren, The Netherlands.
authors.forename: Lubbert
authors.initials: L
authors.lastname: Dijkhuizen
authors.affiliation: Vicuron Pharmaceuticals, via R. Lepetit 34, 21040 Gerenzano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D015870:Gene Expression; D005798:Genes, Bacterial; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D008848:Micromonosporaceae / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D017334:Teicoplanin / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017334:Teicoplanin; D016695:Glycosyltransferases