Issue 30, 2014

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.

Graphical abstract: Bis-chlorination of a hexapeptide–PCP conjugate by the halogenase involved in vancomycin biosynthesis

Supplementary files

Article information

Article type
Communication
Submitted
03 Mar 2014
Accepted
15 Apr 2014
First published
23 Apr 2014
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2014,12, 5574-5577

Author version available

Bis-chlorination of a hexapeptide–PCP conjugate by the halogenase involved in vancomycin biosynthesis

P. C. Schmartz, K. Zerbe, K. Abou-Hadeed and J. A. Robinson, Org. Biomol. Chem., 2014, 12, 5574 DOI: 10.1039/C4OB00474D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements