1. Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus
- Author
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Alessandra Bianchi, Peter de Vreugd, Margherita Sosio, Stefano Donadio, Lubbert Dijkhuizen, Harm Kloosterman, Host-Microbe Interactions, Faculty of Science and Engineering, and Groningen Biomolecular Sciences and Biotechnology
- Subjects
DNA, Bacterial ,Sequence analysis ,Molecular Sequence Data ,Gene Expression ,VANCOMYCIN GROUP ,II THIOESTERASES ,Microbiology ,SEQUENCE ,Open Reading Frames ,Gene cluster ,CYCLIZATION STEPS ,medicine ,GLYCOPEPTIDE BIOSYNTHESIS ,ORFS ,Actinoplanes ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Antibacterial agent ,chemistry.chemical_classification ,biology ,Base Sequence ,STREPTOMYCES-TOYOCAENSIS ,Teicoplanin ,Glycosyltransferases ,AMYCOLATOPSIS-MEDITERRANEI DSM5908 ,Micromonosporaceae ,biology.organism_classification ,Glycopeptide ,Amino acid ,Anti-Bacterial Agents ,carbohydrates (lipids) ,COELICOLOR ,Biochemistry ,chemistry ,Genes, Bacterial ,Multigene Family ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,medicine.drug ,PEPTIDE ANTIBIOTICS - 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.
- Published
- 2004