Glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908: function of a halogenase and a haloperoxidase/perhydrolase.
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.
Puk
Oliver
O
Lehrstuhl für Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, D-72076 Tübingen, Germany.
Huber
Petra
P
Bischoff
Daniel
D
Recktenwald
Jürgen
J
Jung
Günther
G
Süssmuth
Roderich D
RD
van Pée
Karl Heinz
KH
Wohlleben
Wolfgang
W
Pelzer
Stefan
S
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*
D000900:Anti-Bacterial Agents; D006219:Halogens; C087127:balhimycin; D014640:Vancomycin; D006864:Hydrogenase; D006867:Hydrolases