Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d-Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis. Academic Article uri icon

Overview

abstract

  • The bacterial cell wall peptidoglycan contains unusual l- and d-amino acids assembled as branched peptides. Insight into the biosynthesis of the polymer has been hampered by limited access to substrates and to suitable polymerization assays. Here we report the full synthesis of the peptide stem of peptidoglycan precursors from two pathogenic bacteria, Enterococcus faecium and Mycobacterium tuberculosis, and the development of a sensitive post-derivatization assay for their cross-linking by l,d-transpeptidases. Access to series of stem peptides showed that amidation of free carboxyl groups is essential for optimal enzyme activity, in particular the amidation of diaminopimelate (DAP) residues for the cross-linking activity of the l,d-transpeptidase LdtMt2 from M. tuberculosis. Accordingly, construction of a conditional mutant established the essential role of AsnB indicating that this DAP amidotransferase is an attractive target for the development of anti-mycobacterial drugs.

publication date

  • February 21, 2018

Research

keywords

  • Enterococcus faecium
  • Mycobacterium tuberculosis
  • Peptidoglycan
  • Peptidyl Transferases
  • Transaminases

Identity

Scopus Document Identifier

  • 85042216230

Digital Object Identifier (DOI)

  • 10.1002/chem.201706082

PubMed ID

  • 29389045

Additional Document Info

volume

  • 24

issue

  • 22