Aslfm, the D-Aspartate Ligase Responsible for the Addition of D-Aspartic Acid onto the Peptidoglycan Precursor of Enterococcus faecium

Bellais, Samuel; Arthur, Michel; Dubost, Lionnel; Hugonnet, Jean-Emmanuel; Gutmann, Laurent; Heijenoort, Jean van; Legrand, Raymond; Brouard, Jean-Paul; Rice, Louis B.; Mainardi, Jean–Luc

doi:10.1074/jbc.m600114200

Cited by 88 publications

(75 citation statements)

References 37 publications

(32 reference statements)

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“…Thus, Ldt fm tolerated the substitution only in the donor substrate, in contrast to the PBPs that catalyzed peptidoglycan cross-linking with modified donor and acceptor substrates. Modifications of the side chain of peptidoglycan precursors were also shown to be tolerated by PBPs of E. faecalis and S. aureus in previous studies (12,24). (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1A) (23). In E. faecium, D-Asp is added to the precursors by the Asl fm ligase and subsequently partially amidated (12). The bppA1 gene of E. faecalis was cloned under the control of an inducible promoter to generate plasmid pJEH6 and introduced into E. faecium M512 in order to manipulate the structure of the substrate of the cross-linking reaction that can be catalyzed in this mutant by Ldt fm and by the PBPs (28).…”

Section: Resultsmentioning

confidence: 99%

“…Glycine and L-amino acids are incorporated into the side chain of peptidoglycan precursors by transferases of the Fem family that use aminoacyl-tRNAs as the substrate (11). D-Aspartic acid is activated as ␤-aspartyl-phosphate and ligated to the precursors by ATP-dependent ligases belonging to the ATP-Grasp superfamily (12). Synthesis of complete side chains is essential for ␤-lactam resistance mediated by low affinity PBPs in Gram-positive bacteria, in particular methicillin resistance mediated by PBP2a in Staphylococcus aureus (13,14) and penicillin resistance-mediated PBP2X in Streptococcus pneumoniae (15).…”

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confidence: 99%

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Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

Magnet

Arbeloa

Mainardi

et al. 2007

Journal of Biological Chemistry

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The bacterial cell wall peptidoglycan is a net-like macromolecule that surrounds the cytoplasmic membrane (1). The polymer is essential because it supplies the cell with mechanical protection against the osmotic pressure of the cytoplasm. The peptidoglycan subunit contains ␤-1,4-linked N-acetylglucosamine (GlcNAc) 2 and N-acetylmuramic acid (MurNAc) substituted by a peptide stem ( The assembly pathway of peptidoglycan precursors and its mode of polymerization are generally highly conserved in eubacteria. Variations in the structure of peptidoglycan subunits involve mainly the fifth (C-terminal) and third positions of the pentapeptide stem (5). The specificity of peptidoglycan cross-linking enzymes for the donor is the bottleneck that limits emergence of resistance to glycopeptides because the modifications of the precursors that prevent drug binding should be * This work was supported by the program "ACI Microbiologie 2003" from the Fonds National de la Science (Grant ACIM-4-9), the European Community (COBRA, contract LSHM-CT-2003-503335, 6th PCRD), NIAID, National Institutes of Health (Grant R01 AI45626), and the Fondation pour la Recherche Mé dicale. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

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Arbeloa

Mainardi

et al. 2007

Journal of Biological Chemistry

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“…One entails the addition of L-amino acids or glycine from aminoacyl-tRNAs (23,24,62,84,108,114,135,153), while the other one, which is ATP dependent and presumably specific for D-amino acids, proceeds without aminoacyl-tRNAs (15,162,185).…”

Section: Biosynthesis Of Modified Lipid Intermediatesmentioning

confidence: 99%

“…In contrast, in Weissella viridescens (formerly Lactobacillus viridescens), the in vivo addition of L-alanine onto UDP-MurNAc-pentapeptide was substantiated by the presence of a high UDP-MurNAc-hexapeptide pool and the absence of UDP-MurNAc-pentapeptide (83). The peptidyltransferases from Enterococcus faecalis (BppA1 and BppA2) and Enterococcus faecium (Aslfm) were overproduced and purified by using UDP-MurNAc-pentapeptide as an in vitro substrate (15,23,24). However, since the turnover observed with this substrate was very low and since no large UDP-MurNAc-hexapeptide pool level has been encountered in studies of enterococci (20), it can be assumed that in vivo the addition of the bridging amino acids occurs on the lipid intermediates.…”

Section: Biosynthesis Of Modified Lipid Intermediatesmentioning

confidence: 99%

Lipid Intermediates in the Biosynthesis of Bacterial Peptidoglycan

Heijenoort

2007

Microbiol Mol Biol Rev

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172

135

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SUMMARY This review is an attempt to bring together and critically evaluate the now-abundant but dispersed data concerning the lipid intermediates of the biosynthesis of bacterial peptidoglycan. Lipid I, lipid II, and their modified forms play a key role not only as the specific link between the intracellular synthesis of the peptidoglycan monomer unit and the extracytoplasmic polymerization reactions but also in the attachment of proteins to the bacterial cell wall and in the mechanisms of action of antibiotics with which they form specific complexes. The survey deals first with their detection, purification, structure, and preparation by chemical and enzymatic methods. The recent important advances in the study of transferases MraY and MurG, responsible for the formation of lipids I and II, are reported. Various modifications undergone by lipids I and II are described, especially those occurring in gram-positive organisms. The following section concerns the cellular location of the lipid intermediates and the translocation of lipid II across the cytoplasmic membrane. The great efforts made since 2000 in the study of the glycosyltransferases catalyzing the glycan chain formation with lipid II or analogues are analyzed in detail. Finally, examples of antibiotics forming complexes with the lipid intermediates are presented.

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Isomerizations

Asano¹,

Hölsch²

2012

Enzyme Catalysis in Organic Synthesis

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Aslfm, the D-Aspartate Ligase Responsible for the Addition of D-Aspartic Acid onto the Peptidoglycan Precursor of Enterococcus faecium

Cited by 88 publications

References 37 publications

Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

Lipid Intermediates in the Biosynthesis of Bacterial Peptidoglycan

Isomerizations

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