title: Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908: function of a halogenase and a haloperoxidase/perhydrolase.
abstract: Glycopeptides are important clinical emergency antibiotics consisting of a glycosylated and chlorinated heptapeptide backbone. The understanding of the biosynthesis is crucial for development of new glycopeptides. With balhimycin as a model system, this work focuses on the investigation of the putative halogenase gene (bhaA) and the putative haloperoxidase/perhydrolase gene (bhp) of the balhimycin biosynthesis gene cluster. An in-frame deletion mutant in the haloperoxidase/perhydrolase gene bhp (OP696) did not produce balhimycin. Feeding experiments revealed that bhp is involved in the biosynthesis of beta-hydroxytyrosine, a precursor of balhimycin. A bhaA in-frame deletion mutant (PH4) accumulated glycosylated but nonchlorinated balhimycin variants. The mutants indicated that only the halogenase BhaA is required for chlorination of balhimycin. Nonglycosylated and/or nonhalogenated metabolites can serve as starting points for combinatorial approaches for novel glycopeptides.
authors.affiliation: Lehrstuhl für Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, D-72076 Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Puk
authors.forename: Petra
authors.initials: P
authors.lastname: Huber
authors.forename: Daniel
authors.initials: D
authors.lastname: Bischoff
authors.forename: Jürgen
authors.initials: J
authors.lastname: Recktenwald
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: van Pée
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.forename: Stefan
authors.initials: S
authors.lastname: Pelzer
mesh_terms: D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry*; D017353:Gene Deletion; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006219:Halogens / Q000378:metabolism; D006864:Hydrogenase / Q000378:metabolism*; D006867:Hydrolases / Q000378:metabolism*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010957:Plasmids / Q000235:genetics; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D006219:Halogens; C087127:balhimycin; D014640:Vancomycin; D006864:Hydrogenase; D006867:Hydrolases