The Gene Cluster for the Biosynthesis of the Glycopeptide Antibiotic A40926 by Nonomuraea Species
| Autor: | Sofia Stinchi, Fabrizio Beltrametti, Ameriga Lazzarini, Margherita Sosio, Stefano Donadio |
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| Rok vydání: | 2003 |
| Předmět: |
Sequence analysis
medicine.drug_class Mutant Molecular Sequence Data Clinical Biochemistry Glycopeptide antibiotic Biology Mannosyltransferases Peptides Cyclic Biochemistry Open Reading Frames Gene cluster Actinomycetales Drug Discovery medicine Amino Acid Sequence ORFS Peptide Synthases Protein Precursors Molecular Biology Genetics Pharmacology Molecular Structure Glycopeptides General Medicine Glycopeptide Anti-Bacterial Agents Open reading frame Mannosylation Multigene Family Mutation Molecular Medicine Teicoplanin Oligopeptides |
| Zdroj: | Chemistry & Biology. 10(6):541-549 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/s1074-5521(03)00120-0 |
| Popis: | The glycopeptide A40926 is the precursor of dalbavancin, a second-generation glycopeptide currently under clinical development. The dbv gene cluster, devoted to A40926 biosynthesis, was isolated and characterized from the actinomycete Nonomuraea species ATCC39727. From sequence analysis, 37 open reading frames (ORFs) participate in A40926 biosynthesis, regulation, resistance, and export. Of these, 27 ORFs find a match in at least one of the previously characterized glycopeptide gene clusters, while 10 ORFs are, so far, unique to the dbv cluster. Putative genes could be identified responsible for some of the tailoring steps (attachment of glucosamine, sugar oxidation, and mannosylation) expected during A40926 biosynthesis. After constructing a Nonomuraea mutant by deleting dbv ORFs 8 to 10, the novel compound dechloromannosyl-A40926 aglycone was isolated. |
| Databáze: | OpenAIRE |
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