We report here the first direct assessment of the specificity of a class of peptidoglycan cross-linking enzymes, the L,Dtranspeptidases, for the highly diverse structure of peptidoglycan precursors of Gram-positive bacteria. The lone functionally characterized member of this new family of active site cystein peptidases, Ldt fm from Enterococcus faecium, was previously shown to by-pass the D,D-transpeptidase activity of the classical penicillin-binding proteins (PBPs) leading to high-level

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... resistance to glycopeptide and β-lactam antibiotics. Ldt fm homologues from Bacillus subtilis (Ldt Bs ) and E. faecalis (Ldt fs ) were found here to cross-link their cognate disaccharidepeptide subunits containing mesodiaminopimelic acid (mesoDAP 3 ) and L-Lys 3 -L-Ala-Ala at the third position of the stem peptide, respectively, instead of L-Lys 3 -D-iAsn in E. faecium. Ldt fs differed from Ldt fm and