title: Bis-chlorination of a hexapeptide-PCP conjugate by the halogenase involved in vancomycin biosynthesis.
abstract: Vancomycin is an important nosocomial antibiotic containing a glycosylated, cross-linked and doubly chlorinated heptapeptide backbone. During the biosynthesis of the vancomycin aglycone, two β-hydroxytyrosine (Bht) residues are inserted at positions-2 and -6 into the heptapeptide backbone by a non-ribosomal peptide synthetase. A single flavin-dependent chlorinase (VhaA) is responsible for chlorinating both Bht residues at some ill-defined point in the assembly process. We show here using in vitro assays that VhaA is able to introduce a chlorine atom into each aromatic ring of both Bht residues at positions-2 and -6 of a peptide carrier protein-bound hexapeptide. The results suggest that VhaA can recognize and chlorinate two quite different sites within a linear hexapeptide intermediate during vancomycin biosynthesis.
authors.affiliation: Chemistry Department, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. schmartz@oci.uzh.ch kabu@oci.uzh.ch khadeed@oci.uzh.ch robinson@oci.uzh.ch.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Schmartz
authors.forename: Katja
authors.initials: K
authors.lastname: Zerbe
authors.forename: Khaled
authors.initials: K
authors.lastname: Abou-Hadeed
authors.forename: John A
authors.initials: JA
authors.lastname: Robinson
mesh_terms: D002851:Chromatography, High Pressure Liquid; D054879:Halogenation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014640:Vancomycin / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D011506:Proteins; D014640:Vancomycin; D010088:Oxidoreductases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase