Synthetic tripeptides as alternate substrates of murein peptide ligase (Mpl)

Enantioselective synthesis of α-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan

“…4 The importance of the MppA activity is nicely shown by the results obtained by Hervé et al with the tripeptide (S)-Ala-γ-(R)-Glu-ε-(R)-Lys. In E. coli, the first steps of incorporation into PG of tripeptides analogous to (S)-Ala-γ-(R)-Glu-meso-A 2 pm depend on the MppA and Mpl activities, catalyzing the tripeptide uptake, and the synthesis of UDP-MurNActripeptide, respectively.…”

“…30 In contrast to most transport systems, which are tightly regulated, the oligopeptide permease genes are expressed constitutively. 4,31 Thus, an incorporation experiment with 3RS was done with a high tripeptide concentration (500 µg mL −1 , 1 mM) and a lower glucose concentration (0.2% instead of 0.5%) using minimal medium. 32 The effect of glucose amount on the expression of MppA and Mpl is not known but incorporation experiments with the natural and modified murein tripeptides described in the literature (Table 2) are mostly performed in minimal medium supplemented with only 0.2% glucose.…”

“…2) in the tripeptide (S)-Ala-γ-(R)-Glumeso-A 2 pm by derivatives of lanthionine 2 (Fig. [2][3][4] The incorporation of the diastereomers of tripeptides 3 and 4 (Fig. Modified amino acids (A 2 pm and Lys derivatives) in the form of tripeptide analogs of (S)-Ala-γ-(R)-Glu-meso-A 2 pm can be introduced in vivo by the use of the permeases and Mpl activity of E. coli to allow the biosynthesis of modified UDP-MurNActripeptides.…”

Lasso Peptides and Murein Peptide Ligase Inhibitors as Novel Anti-Mycobacterial Agents

“…The choice of potential inhibitors of Mpl was based on structural analogy with the putative natural peptide substrates identified in E.coli [4,5]. These small peptides have been synthesised via solid-phase synthesis and have been tested using M. aurum through the SpotI whole-cell high-throughput screening assay [6].…”

“…Recently, among the class of lasso peptides, interesting stable cyclic peptides of bacterial origin were reported, including the anti-mycobacterial lariatins A and B, followed by the newly-discovered anti-TB pseudo-lasso peptide lassomycin [1][2][3]. Furthermore the identification in M. tuberculosis of an orthologue of an enzyme found in E. coli [4,5] involved in peptidoglycan recycling encouraged us to try to identify and evaluate its activity and find potential inhibitors. …”