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Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d ‐Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis
Author(s) -
Ngadjeua Flora,
Braud Emmanuelle,
Saidjalolov Saidbakhrom,
Iannazzo Laura,
Schnappinger Dirk,
Ehrt Sabine,
Hugonnet JeanEmmanuel,
MenginLecreulx Dominique,
Patin Delphine,
EthèveQuelquejeu Mélanie,
Fonvielle Matthieu,
Arthur Michel
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201706082
Subject(s) - peptidoglycan , mycobacterium tuberculosis , enterococcus faecium , microbiology and biotechnology , chemistry , biochemistry , bacterial cell structure , bacteria , cell wall , enzyme , antibiotics , tuberculosis , biology , medicine , genetics , pathology
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 Ldt Mt2 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.