Glycopeptide Biosynthesis in Amycolatopsis mediterranei DSM5908 Function of a Halogenase and a Haloperoxidase/Perhydrolase

Autor: Puk, Oliver, Huber, Petra, Bischoff, Daniel, Recktenwald, Jürgen, Jung, Günther, Süßmuth, Roderich D, van Pée, Karl-Heinz, Wohlleben, Wolfgang, Pelzer, Stefan
Jazyk: angličtina
Zdroj: Chemistry & Biology. (2):225-235
ISSN: 1074-5521
DOI: 10.1016/S1074-5521(02)00101-1
Popis: 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 β-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.
Databáze: OpenAIRE