Nisin and Novel Lantibiotics

Proceedings of the First International Workshop on Lantibiotics April 15-18, 1991 Physikzentrum Bad Honnef, F. R. G.

Edited by Giinther Jung Institut fur Organische Chemie Universitat Tubingen Auf der Morgenstelle 18 D-7400 Tubingen Germany and Hans-Georg Sahl Institut fur Medizinische Mikrobiologie Universitat Bonn Sigmund-Freud-Str. 25 D-5300 Bonn Germany

ESCOM Leiden 1991

Contents
Preface Contents Abbreviations Introduction Lantibiotics: a survey Gunther Jung 1. 1.1. Conformation of lantibiotics The spatial structure of nisin in aqueous solution Frank J. M. van de Ven, Henno W. van den Hooven, Ruud N. H. Konings and Cornelis W. Hilbers NMR studies of the solution structure of nisin A and related peptides Lu-Yun Lian, Weng C. Chan, S. David Morley, Gordon C. K. Roberts, Barrie W. Bycroft and David Jackson Conformations of nisin and its fragments using synthesis, NMR and computer simulations Murray Goodman, Darryl E. Palmer, Dale Mierke, Seonggu Ro, Kenichi Nunami, Tateaki Wakamiya, Koichi Fukase, Shingo Horimoto, Manabu Kitazawa, Hiroshi Fujita, Akira Kubo and Tetsuo Shiba Structure of cinnamycin (Ro 09-0198) in solution Horst Kessler, Stephan Seip, Thomas Wein, Stefan Steuernagel and Martin Will The three-dimensional solution structure of gaUidermin determined by NMRbased molecular graphics Stefan Freund, Gunther Jung, Oliver Gutbrod, Gerd Folkers and William A. Gibbons NMR and circular dichroism studies on Pep5 Stefan Freund, Gunther Jung, William A. Gibbons and Hans-Georg Sahl Structure elucidation of lantibiotics Structure of the lanthionine peptides nisin, ancovenin and lanthiopeptin Tetsuo Shiba, Tateaki Wakamiya, Koichi Fukase, Yasuyuki Ueki, Tadashi Teshima and Masahiro Nishikawa NMR and activity studies of nisin degradation products Harry S. Rollema, Paula Both and Roland J. Siezen v ix xiii

35

1.2.

43

1.3.

59

1.4. 1.5.

76 91

1.6.

103

2. 2.1.

113

2.2.

123

Contents 2.3. Duramycin B and C, two new lanthionine-containing antibiotics as inhibitors of 131 phospholipase A2, and structural revision of duramycin and cinnamycin Andreas Fredenhagen, Fritz Mdrki, Gabriele Fendrich, Walter Marki, Johannes Gruner, Jan van Oostrum, Fritz Raschdorf and Heinrich H. Peter 2.4. Structure elucidation of the tricyclic lantibiotic Pep5 containing eight positively 141 charged amino acids Roland Kellner, Gunther Jung and Hans-Georg Sahl 2.5. NMR-spectroscopic investigations on mersacidin 159 Herbert Kogler, Markus Bauch, Hans- Wolfram Fehlhaber, Christian Griesinger, Wolfgang Schubert and Volker Teetz 2.6. Isolation and partial structure of streptococcin A-FF22 171 Ralph W. Jack and John R. Tagg 2.7. Frequency of lantibiotic production among coagulase-negative staphylococci: re- 180 isolation of epidermin Angelika Prey, Roland Kellner, Gunther Jung and Hans-Georg Sahl 3. 3.1. Chemical synthesis of lantibiotics and prelantibiotics Studies on chemical synthesis of the lanthionine peptide nisin 189 Tateaki Wakamiya, Koichi Fukase, Akihiko Sano, Kuniaki Shimbo, Manabu Kitazawa, Shingo Horimoto, Hiroshi Fujita, Akira Kubo, Yasushi Maeshiro and Tetsuo Shiba 3.2. Synthesis and characterization of pro- and prepeptides related to nisin and sub- 204 tilin Barrie W. Bycroft, Weng C. Chan and Gordon C. K. Roberts 3.3. Synthesis and conformational analysis of lantibiotic leader-, pro- and pre- 218 peptides Annette G. Beck-Sickinger and Gunther Jung Genetic analysis of nisin production Physical and genetic analysis of the ckromosomally located transposon Tn5301, 231 responsible for nisin biosynthesis Helen M. Dodd, Nikki Horn, Simon Swindell and Michael J. Gasson 4.2. Molecular analysis and evolution of conjugative transposons encoding nisin pro- 243 duction and sucrose fermentation in Lactococcus lactis Peter J. G. Rauch, Marke M. Beerthuyzen and Willem M. de Vos 4.3. Expression of wild-type and mutant nisin genes in Lactococcus lactis 250 Oscar P. Kuipers, Wyanda M. G. J. Yap, Harry S. Rollema, Marke M. Beerthuyzen, Roland J. Siezen and Willem M. de Vos 4.4. A natural nisin variant 260 Tytti Graeffe, Helena Rintala, Lars Paulin and Per Saris 4. 4.1.

Contents Genes involved in biosynthesis of lantibiotics The operon-like organisation of lantibiotic epidermin biosynthesis genes Norbert Schnell, Germar Engelke, Johannes Augustin, Ralf Rosenstein, Friedrich Gotz and Karl-Dieter Entian 5.2. Identification of epidermin biosynthetic genes by complementation studies and heterologous expression Johannes Augustin, Ralf Rosenstein, Thomas Kupke, Uschi Schneider, Norbert Schnell, Germar Engelke, Karl-Dieter Entian and Friedrich Gotz 5.3. Biosynthesis and mechanism of action of nisin and subtilin J. Norman Hansen, Yong Joon Chung, Wei Liu and Mark T. Steen 5.4. Isolation and characterization of the cinnamycin structural gene Karl-Dieter Entian and Cortina Kaletta 5.5. An operon-like structure of genes involved in subtilin biosynthesis Cortina Kaletta, Cora Klein, Norbert Schnell and Karl-Dieter Entian 5.6. Genetic analysis of the producer self-protection mechanism ("immunity") against Pep5 Michaela Reis and Hans-Georg Sahl 6. 6.1. 5. 5.1.

269

277

287 303 309 320

Biosynthetic precursors Isolation of Pep5 prepeptides in different stages of modification 332 Hans-Georg Sahl, Michaela Reis, Monika Eschbach, Christiane Szekat, Annette G. Beck-Sickinger, Jorg Metzger, Stefan Stevanovic and Gunther Jung

Mode of action of lantibiotics Pore formation in bacterial membranes by cationic lantibiotics 347 Hans-Georg Sahl 7.2. Mechanism of channel-formation by lantibiotics in black lipid membranes 359 Roland Benz, Gunther Jung and Hans-Georg Sahl 7.3. The mechanism of action of the lantibiotic nisin in artificial membranes 373 Tjakko Abee, Fu H. Gao and Wil N. Konings 7.4. Induction of autolysis of Staphylococcus simvlans 22 by Pep5 and nisin and 386 influence of the cationic peptides on the activity of the autolytic enzymes Gabriele Bierbaum and Hans-Georg Sahl 8. 8.1. Fermentation and purification of lantibiotics Microbial manipulation of nisin biosynthesis and fermentation 397 Luc De Vuyst and Erick J. Vandamme 8.2. Optimization of fermentation and purification of gallidermin and epidermin 410 Volker Ungermann, Klaus Goeke, Hans-Peter Fiedler and Hans Zdhner 8.3. Strategy for purification of lantibiotics 422 Hermann Allgaier, Joachim Walter, Michael Schluter and Rolf-Gunther Werner

7. 7.1.

XI

Contents 9. Applications of lantibiotics 9.1. Applications of nisin: a literature survey 434 Ernst Molitor and Hans-Georg Sahl 9.2. Application of nisin A and nisin Z in dairy technology 440 Jeroen Hugenholtz and Gerrie J. C. M. de Veer 9.3. Chemotherapeutic properties of mersacidin in vitro and in vivo 448 Michael Limbert, Dieter Isert, Norbert Klesel, Astrid Markus, Gerhard Seibert, Sukumar Chatterjee, Dipak K. Chatterjee, Rajendra H. Jani and Binmal N. Ganguli Appendix Appendix: definitions and nomenclature of lantibiotics Willem M. de Vos, Gunther Jung and Hans-Georg Sahl List of participants Author index Subject index

457

464 470 472

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