title: The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by nonomuraea species.
abstract: 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.
authors.affiliation: Vicuron Pharmaceuticals, via R. Lepetit 34, 21040, Gerenzano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.forename: Sofia
authors.initials: S
authors.lastname: Stinchi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Beltrametti
authors.forename: Ameriga
authors.initials: A
authors.lastname: Lazzarini
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
mesh_terms: D000192:Actinomycetales / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D006020:Glycopeptides / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008364:Mannosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family / Q000502:physiology*; D009154:Mutation; D009842:Oligopeptides / Q000096:biosynthesis; D016366:Open Reading Frames / Q000502:physiology*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D017334:Teicoplanin / Q000031:analogs & derivatives
chemical_list: C054981:A 40926; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011498:Protein Precursors; C057568:A 40926 aglycone; D017334:Teicoplanin; C469289:dalbavancin; D008364:Mannosyltransferases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase