Structure elucidation of antimicrobial polypeptides, their ribosomal biosynthesis and posttranslational modifications

Microcins and lantibiotics are families of polypeptides, synthesized via precursor-proteins and posttranslational modifications at serine, threonine and cysteine residues.  Thereby side chains and backbone are transformed to give sulphide rings, 2,3-didehydroamino acids, D-amino acids, oxazole and thiazol rings. 3D-structures of the resulting conformationally restricted polypeptides have been elucidated. In cooporation with microbiologists (F.Götz and H.-G. Sahl), their biosynthesis, the sequences of prepeptide intermediates, sequential analogues and importantly the novel peptide modifying enzymes were elucidated. Thus the molecular basis of a novel protein engineering with defined construction of unusually modified peptides was established.

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(1988). Prepeptide Sequence of Epidermin, a Ribosomally Synthesized Polypeptide Antibiotic Containing four Sulphide-Rings, Nature 333,276-278.

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A. Bayer, S. Freund, G. Nicholson und G. Jung (1993). Posttranslational Backbone Modifications in the Ribosomal Biosynthesis of the Glycine-Rich Antibiotic Microcin B17, Angew. Chern. 105, 1410-1413; Angew. Chern. Int. Ed. Engl.32, 1336-1339.

M. Skaugen, J. Nissen-Meyer, G. Jung, S. Stevanovic, K.Sletten, C.I Mortvedt Abild-
gaard, and I.F. Nes (1994). In vivo Conversion of L-Serine to D-Alanine in a Ribosomally Synthesized Polypeptide, J. Biol. Chern. 269, 27183-27185.

A. Bayer, S. Freund, and G. Jung (1995). Post-translational Heterocyclic Backbone Modifications in the 43-Peptide Antibiotic Microcin B17, Structure Elucidation and NMR Study of a 13C, 15N-Iabelled Gyrase Inhibitor, Eur. J. Biochem.234, 414-426.

T. Kupke, C. Kempter, G. Jung, and F. Götz (1995). Oxidative Decarboxylation of Peptides Catalyzed by Flavoprotein Epi D: Determination of Substrate Specificity Using Peptide Libraries and Neutral Loss Mass Spectrometry, J. Biol. Chem. 270, 11282-11289.

B.Ottenwälder, T. Kupke, S. Brecht, V. Gnau, J. Metzger, G. Jung, and F. Götz (1995).
Isolation and Characterization of Genetically Engineered Gallidermin and Epi-
dermin Analogs,
Appl. Environ. Microbiol. 61, 38943903.

N. Zimmermann, J.W. Metzger, and G. Jung (1995). The Tetracyclic Lantibiotic Actagardine, 1NMR and 13C-NMR Assignments and Revised Primary Structure, Eur. J. Biochem., 228, 786-797.

G. Videnov, D. Kaiser, C. Kempter, M. Brooks, and G. Jung (1996). Synthesis of the DNA Gyrase Inhibitor Microcin B17, a 43-Peptide Antibiotic with Eight Heteroaromatic Rings in the Backbone, Angew. Chem., 108, 1607-1609; Angew. Chem. Int. Ed. Engl. 35, 1506-1508.

G. Bierbaum, C. Szekat, M. Josten, C. Heidrich, C. Kempter, G. Jung, and H.-G. Sahl
(1996). Engineering of a Novel Thioether Bridge and Role of Modified Residues in the
Lantibiotic Pep5
, Appl. Environm. Microbiol., 62, 385-392.

F.J.M. van de Ven and G. Jung (1996). Structures of Lantibiotics Studied by NMR , Antonie van Leeuwenhoek 1. Microbiol., 69, 99-107.

D.G. Schmid, F. Majer, T. Kupke, and G. Jung (2002). Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry to Reveal the Substrate Specificity of the  Peptidyl-cysteine Decarboxylase EpiD, Rap. Comm. Mass Spectr. 16, 1779-1784.

G. Jung (2006). Enzyme-Catalyzed Sulfide Ring Formation in Lantibiotics, Angew. Chem. 118, 2-5; Angew. Chem. Int. Ed. 45, 5919-5921.

Biosynthesis of McB17

Solution Structure of Gallidermin and Sequence of Epidermin

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