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Accueil > Départements > Microbiologie > Muriel GONDRY : Enzymologie et Biosynthèse Peptidique Non Ribosomale



  • A. Malabirade, J. Morgado-Brajones, S. Trépout, F. Wien, I. Marquez, J. Seguin, S. Marco, M. Velez, et A. Véronique, « Membrane association of the bacterial riboregulator Hfq and functional perspectives », Scientific Reports, vol. 7, nᵒ 1, p. 10724, 2017.
    Résumé : Hfq is a bacterial RNA binding protein that carries out several roles in genetic expression regulation, mainly at the post-transcriptional level. Previous studies have shown its importance in growth and virulence of bacteria. Here, we provide the direct observation of its ability to interact with membranes. This was established by co-sedimentation assay, cryo-transmission electron (cryo-TEM) and atomic force (AFM) microscopies. Furthermore, our results suggest a role for its C-terminus amyloidogenic domain in membrane disruption. Precisely, AFM images of lipid bilayers in contact with Hfq C-terminus fibrils show the emergence of holes with a size dependent on the time of interaction. Cryo-TEM observations also show that liposomes are in contact with clusters of fibrils, with occasional deformation of the vesicles and afterward the apparition of a multitude of tiny vesicles in the proximity of the fibrils, suggesting peptide-induced breakage of the liposomes. Finally, circular dichroism spectroscopy demonstrated a change in the secondary structure of Hfq C-terminus upon interaction with liposomes. Altogether, these results show an unexpected property of Hfq and suggest a possible new role for the protein, exporting sRNA outside of the bacterial cell.
    Mots-clés : BIOSYN, MICROBIO.

  • M. Moutiez, P. Belin, et M. Gondry, « Aminoacyl-tRNA-Utilizing Enzymes in Natural Product Biosynthesis », Chemical Reviews, 2017.
    Résumé : Aminoacyl-tRNAs were long thought to be involved solely in ribosome-dependent protein synthesis and essential primary metabolism processes, such as targeted protein degradation and peptidoglycan synthesis. About 10 years ago, an aminoacyl-tRNA-dependent enzyme involved in the biosynthesis of the antibiotic valanimycin was discovered in a Streptomyces strain. Far from being an isolated case, this discovery has been followed by the description of an increasing number of aminoacyl-tRNA-dependent enzymes involved in secondary metabolism. This review describes the three groups of aminoacyl-tRNA-dependent enzymes involved in the synthesis of natural products. Each group is characterized by a particular chemical reaction, and its members are predicted to share a specific fold. The three groups are cyclodipeptide synthases involved in diketopiperazine synthesis, LanB-like dehydratases involved in the posttranslational modification of ribosomal peptides, and transferases from various biosynthesis pathways.
    Mots-clés : BIOSYN, MICROBIO.


  • I. B. Jacques, M. Moutiez, J. Witwinowski, E. Darbon, C. Martel, J. Seguin, E. Favry, R. Thai, A. Lecoq, S. Dubois, J. - L. Pernodet, M. Gondry, et P. Belin, « Analysis of 51 cyclodipeptide synthases reveals the basis for substrate specificity », Nature Chemical Biology, vol. 11, nᵒ 9, p. 721-727, 2015.
    Résumé : Cyclodipeptide synthases (CDPSs) constitute a family of peptide bond-forming enzymes that use aminoacyl-tRNAs for the synthesis of cyclodipeptides. Here, we describe the activity of 41 new CDPSs. We also show that CDPSs can be classified into two main phylogenetically distinct subfamilies characterized by specific functional subsequence signatures, named NYH and XYP. All 11 previously characterized CDPSs belong to the NYH subfamily, suggesting that further special features may be yet to be discovered in the other subfamily. CDPSs synthesize a large diversity of cyclodipeptides made up of 17 proteinogenic amino acids. The identification of several CDPSs having the same specificity led us to determine specificity sequence motifs that, in combination with the phylogenetic distribution of CDPSs, provide a first step toward being able to predict the cyclodipeptides synthesized by newly discovered CDPSs. The determination of the activity of ten more CDPSs with predicted functions constitutes a first experimental validation of this predictive approach.
    Mots-clés : ACTINO, Amino Acid Motifs, Bacterial Proteins, BIOCELL, BIOSYN, Computational Biology, Cyclization, Databases, Genetic, Dipeptides, Escherichia coli, Fungal Proteins, gene expression, MICROBIO, Molecular Sequence Data, Peptide Biosynthesis, Nucleic Acid-Independent, Peptide Synthases, Peptides, Cyclic, Phylogeny, Protein Structure, Tertiary, Recombinant Proteins, RNA, Transfer, Amino Acyl, Substrate Specificity.
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Publications Principales avant 2015

Moutiez M., Schmitt E., Seguin J., Thai R., Favry E., Belin P., Mechulam Y., Gondry M. (2014). Unravelling the mechanism of non-ribosomal peptide synthesis by cyclodipeptide synthases. Nat. Commun. 5:5141 doi : 10.1038/ncomms6141

Moutiez M., Seguin J., Fonvielle M., Belin P., Jacques I.B., Favry E., Arthur M., Gondry M. (2014). Specificity determinants for the two tRNA substrates of the cyclodipeptide synthase AlbC from Streptomyces noursei. Nucl. Acids Res. 42, 7247–7258

Jacques I., Seguin J., Moutiez M., Favry E., Gondry M., Belin P. (2014). Expanding the diversity of diketopiperazines biosynthesized by cyclodipeptide synthases. New Biotechnol. 31S, S74-S75 doi : 110.1016/j.nbt.2014.05.1782

Fonvielle M., Le Du M.-H., Lequin O., Lecoq A., Jacquet M., Thai R., Dubois S., Grach G., Gondry M., Belin P. (2013). Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121 : insights from biochemical studies and crystal structures. J. Biol. Chem. 288, 17347-17359

Nozach H., Fruchart-Gaillard C., Fenaille F., Beau F., Ramos O.H., Douzi B., Saez N.J., Moutiez M., Servent D., Gondry M., Thai R., Cuniasse P., Vincentelli R., Dive V. (2013). High throughput screening identifies disulfide isomerase DsbC as a very efficient partner for recombinant expression of small disulfide-rich proteins in E. coli. Microb. Cell Fact. 12, 37

Gueneau E., Dherin C., Legrand P., Tellier-Lebegue C., Gilquin B., Bonnesoeur P., Londino F., Quemener C., Le Du M.-H., Marquez J. A., Moutiez M., Gondry M., Boiteux S., Charbonnier J.-B. (2013). Structures of the MutLa C-terminal domain reveal how Mlh1 recruits exonuclease I and contributes to PMS1 endonuclease active site. Nat. Struct. Mol. Biol. 20, 461-468

Belin P., Moutiez M., Lautru S., Seguin J., Pernodet J.-L., Gondry M. (2012). The nonribosomal synthesis of diketopiperazines in tRNA-dependent cyclodipeptide synthase pathways. Nat. Prod. Rep. 29, 961-979

Seguin J., Moutiez M., Li Y., Belin P., Lecoq A., Fonvielle M., Charbonnier J.-B., Pernodet J.-L., Gondry M. (2011). Nonribosomal peptide synthesis in animals : the cyclodipeptide synthase of Nematostella. Chem. Biol. 18, 1362-1368

Sauguet L., Moutiez M., Li Y., Belin P., Seguin J., Le Du M.-H., Thai R., Masson C., Fonvielle M., Pernodet J.-L., Charbonnier J.-B., Gondry M. (2011). Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis. Nucl. Acids Res. 39, 4475-4489

Gondry M., Sauguet L., Belin P., Thai R., Amouroux R., Tellier C., Tuphile K, Jacquet M., Braud S., Courçon M., Masson C., Dubois S., Lautru S., Lecoq A., Hashimoto S.-i, Genet R., Pernodet J.-L. (2009). Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5, 414-420

Belin P., Le Du M.-H., Fielding A., Lequin O, Jacquet M., Charbonnier J.-B., Lecoq A., Thai R., Courçon M., Masson C., Dugave C., Genet R., Pernodet J.-L., Gondry M. (2009). Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106, 7426-7431

Juguet M., Lautru S., Francou F.-X., Nezbedová S., Leblond P., Gondry M., Pernodet J.-L. (2009). An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens. Chem. Biol. 16, 421-431

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