Molecular Genetics of Biosynthesis

  • Ralph W. Jack
  • Gabriele Bierbaum
  • Hans-Georg Sahl
Part of the Biotechnology intelligence unit book series (BIOIU)

Abstract

The lantibiotic nisin had already been established as a food preservative when I the first research into its biosynthesis was initiated by Hurst in 1966.1 At that time, most scientists agreed that polypeptide antibiotics, e.g.,bacitracin (see chapter 1), which contain unusual amino acids, were synthesized by nonribosomal mechanisms, since there are no codons in the genetic code that permit integration of the rare amino acids into the peptide backbone.2 In contrast to this hypothesis, the first studies with inhibitors of RNA and ribosomal protein biosynthesis, as well as experiments employing labeled Ser, Thr and Cys demonstrated that the ring forming lanthionine (Lan) and methyllanthionine (MeLan) residues in nisin derive from the proteinogenic amino acids Ser, Thr and Cys.1,3,4 The first part of this chapter will describe this unusual pathway that leads to the biosynthesis of the modified residues in lantibiotics and microcin B17. The ultimate evidence for the ribosomal biosynthesis mechanism, the sequence of the structural gene of epidermin which contains the codons for Ser, Thr and Cys in those positions that are occupied by Lan and MeLan in the mature lantibiotic,5 was presented nearly two decades after those pioneering experiments of Hurst and Ingram and the structural genes of nisin, subtilin and Peps followed within one year.6–8 The cloning of these structural genes led to a very fruitful period of lantibiotic research in the early 1990s, which includes the discovery of the lantibiotic biosynthetic gene clusters, whose molecular architecture and regulation will be presented in detail below. The biosynthesis of microcin B17 will also be described in this chapter. Here, the structural gene was discovered in 19899 before the structure of the mature peptide had been elucidated.10

Keywords

Lipase Bacillus Polypeptide Dehydration Lactobacillus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hurst A. Biosynthesis of the antibiotic nisin by whole Streptococcus lactis organisms. J Gen Microbiol 1966; 44: 209–220.PubMedGoogle Scholar
  2. 2.
    Bodanszky M, Perlman D. Are peptide antibiotics small proteins? Nature 1964; 204: 840–844.PubMedCrossRefGoogle Scholar
  3. 3.
    Ingram LC. Synthesis of the antibiotic nisin: Formation of lanthionine and ß-methyl-lanthionine. Biochim Biophys Acta 1969; 184: 216–219.PubMedCrossRefGoogle Scholar
  4. 4.
    Ingram LC. A ribosomal mechanism of synthesis for peptides related to nisin. Biochim Biophys Acta 1970; 224: 263–265.PubMedCrossRefGoogle Scholar
  5. 5.
    Schnell N, Entian K-D, Schneider U et al. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature 1988; 333: 276–278.PubMedCrossRefGoogle Scholar
  6. 6.
    Buchmann GW, Banerjee S, Hansen JN. Structure, expression, and evolution of a gene encoding the precursor of nisin, a small protein antibiotic. J Biol Chem 1988; 263: 16260–16266.Google Scholar
  7. 7.
    Banerjee S, Hansen JN. Structure and expression of a gene encoding the precursor of subtilin, a small protein antibiotic. J Biol Chem 1988; 263: 9508–9514.PubMedGoogle Scholar
  8. 8.
    Kaletta C, Entian K-D, Kellner R et al. Pep5, a new lantibiotic: structural gene isolation and prepeptide sequence. Arch Microbiol 1989; 152: 16–19.PubMedCrossRefGoogle Scholar
  9. 9.
    Genilloud O, Moreno F, Kolter R. DNA sequence, products, and transcriptional pattern of the genes involved in production of the DNA replication inhibitor microcin B17. J Bacteriol 1989; 171: 1126–1135.PubMedGoogle Scholar
  10. 10.
    Bayer A, Freund S, Nicholson G et al. Posttranslational backbone modifications in the ribosomal biosynthesis of the glycine-rich antibiotic microcin B17. Angew Chem Int Ed Engl 1993; 321336–1339.Google Scholar
  11. 11.
    Jung G. Lantibiotics-ribosomally synthesized biologically active polypeptides containing sulfide bridges and a,ß-didehydroamino acids. Angew Chem Int Ed Engl 1991; 30: 1051–1068.CrossRefGoogle Scholar
  12. 12.
    Jung G. Lantibiotics: a survey. In: Jung G, Sahl H-G eds. Nisin and Novel Lantibiotics. Leiden: ESCOM, 1991: 1–34.Google Scholar
  13. 13.
    Sahl H-G, Jack RW, Bierbaum G. Biosynthesis and biological activities of lantibiotics with unique post-translational modifications. Eur J Biochem 1995; 230: 827–853.PubMedCrossRefGoogle Scholar
  14. 14.
    Meyer C, Bierbaum G, Heidrich C et al. Nucleotide sequence of the lantibiotic Pep5 biosynthetic gene cluster and functional analysis of PepP and PepC. Evidence for a role of PepC in thioether formation. Eur J Biochem 1995; 232: 478–489.PubMedCrossRefGoogle Scholar
  15. 15.
    Grabowski R, Hofmeister AEM, Buckel W. Bacterial L-serine dehydratases: a new family of enzymes containing iron-sulfur clusters. TIBS 1993; 18: 297–300.PubMedGoogle Scholar
  16. 16.
    Weil H-P, Beck-Sickinger AG, Metzger J et al. Biosynthesis of the lantibiotic Pep5. Isolation and characterization of a prepeptide containing dehydroamino acids. Eur J Biochem 1990; 194: 217–223.PubMedCrossRefGoogle Scholar
  17. 17.
    Toogood PL. Model studies of lantibiotic biogenesis. Tetrahedron Lett 1993; 34: 7833–7836.CrossRefGoogle Scholar
  18. 18.
    Kupke T, Stevanovics S, Sahl H-G et al. Purification and characterization of EpiD, a flavoprotein involved in the biosynthesis of the lantibiotic epidermin. J Bacteriol 1992; 174: 5354–5361.PubMedGoogle Scholar
  19. 19.
    Kupke T, Kempter C, Gnau V et al. Mass spectroscopic analysis of a novel enzymatic reaction: Oxidative decarboxylation of the lantibiotic precursor peptide EpiA catalyzed by the flavoprotein EpiD. J Biol Chem 1994; 269: 5653–5659.PubMedGoogle Scholar
  20. 20.
    Kupke T, Kempter C, Jung G et al. Oxidative decarboxylation of peptides catalyzed by flavoprotein EpiD. Determination of substrate specificity using peptide libraries and neutral loss mass spectrometry. J Biol Chem 1995; 270: 11282–11289.PubMedCrossRefGoogle Scholar
  21. 21.
    Skaugen M, Nissen-Meyer J, Jung G et al. In vivo conversion of L-serine to D-alanine in a ribosomally synthesized polypeptide. J Biol Chem 1994; 269: 27183–27185.PubMedGoogle Scholar
  22. 22.
    Skaugen M, Abildgaard CIM, Nes IF. Organization and expression of a gene cluster involved in the biosynthesis of the lantibiotic lactocin S. Mol Gen Genet 1997; 253: 674–686.PubMedCrossRefGoogle Scholar
  23. 23.
    Van de Kamp M, van den Hooven HW, Konings RNH et al. Elucidation of the primary structure of the lantibiotic epilancin K7 from Staphylococcus epidermidis K7. Cloning and characterisation of the epilancin-K7-encoding gene and NMR analysis of mature epilancin K7. Eur J Biochem 1995; 230: 587–600.PubMedCrossRefGoogle Scholar
  24. 24.
    Heidrich C, Pag U, Josten M et al. Isolation, characterization and sequence of the novel lantibiotic epicidin 28o and its biosynthetic gene cluster. (submitted).Google Scholar
  25. 25.
    Li Y-M, Milne JC, Madison LL et al. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase. Science 1996; 274: 1188–1193.PubMedCrossRefGoogle Scholar
  26. 26.
    Yorgey P, Lee J, Kördel J et al. Posttranslational modifications in microcin B17 define an additional class DNA gyrase inhibitor. Proc Natl Acad Sci 1994; 91: 4519–4523.PubMedCrossRefGoogle Scholar
  27. 27.
    Bayer A, Freund S, Jung G. Post-translational heterocyclic backbone modifications in the 43-peptide antibiotic microcin B17. Structure elucidation and NMR study of a ‘3C, ’5N-labelled gyrase inhibitor. Eur J Biochem 1995; 234: 414–426.PubMedCrossRefGoogle Scholar
  28. 28.
    Siezen RJ, Kuipers OP, Vos WM. Comparison of lantibiotic gene clusters and encoded proteins. Antonie van Leeuwenhoek 1996; 69: 171–184.PubMedCrossRefGoogle Scholar
  29. 29.
    Bierbaum G, Sahl H-G. Lantibiotics-unusually modified bacteriocin-like peptides from Gram-positive bacteria. Zbl Bakt 1993; 278: 1–22.Google Scholar
  30. 30.
    Jack RW, Tagg JR, Ray B. Bacteriocins of gram-positive bacteria. Microbiol Rev 1995; 59171–200.Google Scholar
  31. 31.
    Jack RW, Sahl H-G. Unique peptide modifications involved in the biosynthesis of lantibiotics. Tibtech 1995; 13269–278.Google Scholar
  32. 32.
    Vos WM, Kuipers OP, Meer JR et al. Maturation pathway of nisin and other lantibiotics: post-translationally modified antimicrobial peptides exported by Gram-positive bacteria. Mol Microbiol 1995; 17: 427–437.Google Scholar
  33. 33.
    Vos WM, Jung G, Sahl H-G. Appendix: definitions and Nomenclature of Lantibiotics. In: Jung G, Sahl H-G eds. Nisin and novel lantibiotics. Leiden: ESCOM, 1991: 457–463.Google Scholar
  34. 34.
    Kaletta C, Entian K-D. Nisin, a peptide antibiotic: cloning and sequencing of the nisA gene and posttranslational processing of its peptide product. J Bacteriol 1989; 171: 1597–1601.PubMedGoogle Scholar
  35. 35.
    Dodd HM, Horn N, Gasson MJ. Analysis of the genetic determinant for production of the peptide antibiotic nisin. J Gen Microbiol 1990; 136: 555–566.Google Scholar
  36. 36.
    Dodd HM, Horn N, Hao Z et al. A lactococcal expression system for engineered nisins. Appl Environ Microbiol 1992; 583683–3693.Google Scholar
  37. 37.
    Steen MT, Chung YJ, Hansen JN. Characterization of the nisin gene as part of a polycistronic operon in the chromosome of Lactococcus lactis ATCC 11454. Appl Environ Microbiol 1991; 57: 1181–1188.PubMedGoogle Scholar
  38. 38.
    Engelke G, Gutowski-Eckel Z, Hammelmann M et al. Biosynthesis of the lantibiotic nisin: Genomic organization and membrane localization of the NisB protein. Appl Environ Microbiol 1992; 58: 3730–3743.PubMedGoogle Scholar
  39. 39.
    Kuipers OP, Beerthuyzen MM, Siezen RJ et al. Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis: requirement of expression of the nisA and nisi genes for producer immunity. Eur J Biochem 1993; 216: 281–292.Google Scholar
  40. 40.
    Van der Meer JR, Polman J, Beerthuyzen MM et al. Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. J Bacteriol 1993; 175: 2578–2588.PubMedGoogle Scholar
  41. 41.
    Engelke G, Gutowski-Eckel Z, Kiesau P et al. Regulation of nisin biosynthesis and immunity in Lactococcus lactis 6F3. Appl Environ Microbiol 1994; 60: 814–825.PubMedGoogle Scholar
  42. 42.
    Siegers K, Entian K-D. Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3. Appl Environ Microbiol 1995; 61: 1082–1089.PubMedGoogle Scholar
  43. 43.
    Mulders JWM, Boerrigter IJ, Rollema HS et al. Identification and characterization of the lantibiotic nisin Z, a structural nisin variant. Eur J Biochem 1991; 201: 581–584.PubMedCrossRefGoogle Scholar
  44. 44.
    Immonen T, Ye S, Ra R et al. The codon usage of the nisZ operon in Lactococcus lactis N8 suggests a non-lactococcal origin of the conjugative nisin-sucrose transposon. DNA Sequence 1995; 5: 203–218.PubMedGoogle Scholar
  45. 45.
    Chung YJ, Steen MT, Hansen JN. The subtilin gene of Bacillus subtilis ATCC 6633 is encoded in an operon that contains a homolog of the hemolysin B transport protein. J Bacteriol 1992; 174: 1417–1422.PubMedGoogle Scholar
  46. 46.
    Chung YJ, Hansen JN. Determination of the sequence of spaE and identification of a promoter in the subtilin (spa) operon in Bacillus subtilis. J Bacteriol 1992; 174: 6699–6702.PubMedGoogle Scholar
  47. 47.
    Klein C, Kaletta C, Schnell N et al. Analysis of genes involved in biosynthesis of the lantibiotic subtilin. Appt Environ Microbiol 1992; 58: 132–142.Google Scholar
  48. 48.
    Klein C, Kaletta C, Entian K-D. Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system. Appl Environ Microbiol 1993; 59: 296–303.PubMedGoogle Scholar
  49. 49.
    Gutowski-Eckel Z, Klein C, Siegers K et al. Growth-phase dependent regulation and membrane localization of SpaB, a protein involved in biosynthesis of the lantibiotic subtilin. Appl Environ Microbiol 1994; 60: 1–11.PubMedGoogle Scholar
  50. 50.
    Klein C, Entian K-D. Genes involved in self-protection against the lantibiotic subtilin produced by Bacillus subtilis ATCC 6633. Appl Environ Microbiol 1994; 60: 2793–2801.PubMedGoogle Scholar
  51. 51.
    Schnell N, Engelke G, Augustin J et al. Analysis of genes involved in the biosynthesis of lantibiotic epidermin. Eur J Biochem 1992; 20:457–68.Google Scholar
  52. 52.
    Peschel A, Götz F. Analysis of the Staphylococcus epidermidis genes epiF, -E, and -G involved in epidermin immunity. J Bacteriol 1996; 178: 531–536.PubMedGoogle Scholar
  53. 53.
    Peschel A, Schnell N, Hille M et al. Secretion of the ‘antibiotics epidermin and gallidermin: sequence analysis of the genes gdmT and gdmH, their influence on epidermin production and their regulation by EpiQ. Mol Gen Genet 1997; 254: 312–318.PubMedCrossRefGoogle Scholar
  54. 54.
    Schnell N, Entian K-D, Götz F et al. Structural gene isolation and prepeptide sequence of gallidermin, a new lanthionine containing antibiotic. FEMS Microbiol Lett 1989; 58: 263–268.CrossRefGoogle Scholar
  55. 55.
    Reis M, Eschbach-Bludau M, Iglesias-Wind MI et al. Producer immunity towards the lantibiotic Peps: Identification of the immunity gene pepi and localization and functional analysis of its gene product. Appt Environ Microbiol 1994; 60: 2876–2883.Google Scholar
  56. 56.
    Hynes WL, Ferretti JJ, Tagg JR. Cloning of the gene encoding streptococcin A-FF22, a novel lantibiotic produced by Streptococcus pyogenes, and determination of its nucleotide sequence. Appt Environ Microbiol 1993; 59: 1969–1971.Google Scholar
  57. 57.
    Hynes WL, Friend VL, Ferretti JJ. Duplication of the lantibiotic structural gene in M-type 49 group A Streptococcus strains producing streptococcin A-M49. Appt Environ Microbiol 1994; 60: 4207–4209.Google Scholar
  58. 58.
    Ross KF, Ronson CW, Tagg JR. Isolation and characterization of the lantibiotic salivaricin A and its structural gene salA from Streptococcus salivarius 2oP3. Appl Environ Microbiol 1993; 59: 2014–2021.PubMedGoogle Scholar
  59. 59.
    Pridmore D, Rekhif N, Pittet A-C et al. Variacin, a new lanthionine-containing bacteriocin produced by Micrococcus varians: comparison to lacticin 481 of Lactococcus lactis. Appl Environ Microbiol 1996; 62: 1799–1802.PubMedGoogle Scholar
  60. 60.
    Piard J-C, Kuipers OP, Rollema HS et al. Structure, organization, and expression of the Ict gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactis. J Biol Chem 1993; 268: 16361–16368.PubMedGoogle Scholar
  61. 61.
    Rince A, Dufour A, Le Pogam S et al. Cloning, expression, and nucleotide sequence of genes involved in production of lactococcin DR, a bacteriocin from Lactococcus lactis, subsp. lactis. Appl Environ Microbiol 1994; 60: 1652–1657.PubMedGoogle Scholar
  62. 62.
    Gilmore MS, Segarra RA, Booth MC. An H1yB-type function is required for expression of the Enterococcus faecalis hemolysin/bacteriocin. Infect Immun 1990; 58: 3914–3923.PubMedGoogle Scholar
  63. 63.
    Gilmore MS, Segarra RA, Booth MC et al. Genetic structure of the Enterococcus faecalis plasmid pADi-encoded cytolytic toxin system and its relationship to lantibiotic determinants. J Bacteriol 1994; 176: 7335–7344.PubMedGoogle Scholar
  64. 64.
    Kaletta C, Entian K-D, Jung G. Prepeptide sequence of cinnamycin (Ro 09–0198): the first structural gene of a duramycin-type lantibiotic. Eur J Biochem 1991; 199: 411–415.PubMedCrossRefGoogle Scholar
  65. 65.
    Bierbaum G, Brötz H, Koller H-P et al. Cloning, sequencing and production of the lantibiotic mersacidin. FEMS Microbiol Lett 1995; 127: 121–126.PubMedCrossRefGoogle Scholar
  66. 66.
    Garrido MC, Herrero M, Kolter R et al. The export of the DNA replication inhibitor microcin B17 provides immunity for the host cell. EMBO J 1988; 7: 1853–1862.PubMedGoogle Scholar
  67. 67.
    Hâvarstein LS, Diep DB, Nes IF. A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol Microbiol 1995; 16: 229–240.PubMedCrossRefGoogle Scholar
  68. 68.
    Venema K, Kok J, Marugg JD et al. Functional analysis of the pediocin operon of Pediococcus acidilactici PACi.o: PedB is the immunity protein and PedD is the precursor processing enzyme. Mol Microbiol 1995; 17: 515–522.PubMedCrossRefGoogle Scholar
  69. 69.
    Tsai H-J, Sandine WE. Conjugal transfer of nisin plasmid genes from Streptococcus lactis 7962 to Leuconostoc dextranicum 181. Appl Environ Microbiol 1987; 53: 352–357.PubMedGoogle Scholar
  70. 70.
    Rauch PJG, de Vos WM. Characterization of the novel nisin-sucrose conjugative transposon Tn5276 and its insertion in Lactococcus lactis. J Bacteriol 1992; 174: 1280–1287.PubMedGoogle Scholar
  71. 71.
    Horn N, Swindell S, Dodd H et al. Nisin biosynthesis genes are encoded by a conjugative transposon. Mol Gen Genet 1991; 228:129–135.Google Scholar
  72. 72.
    De Vos WM, Mulders JWM, Siezen RJ et al. Properties of nisin Z and distribution of its gene, nisZ, in Lactococcus lactis. Appl Environ Microbiol 1993; 59: 213–218.PubMedGoogle Scholar
  73. 73.
    Graeffe T, Rintala H, Paulin L et al. A natural nisin variant. In: Jung G, Sahl H-G eds. Nisin and Novel Lantibiotics. Leiden: ESCOM, 1991: 260–268.Google Scholar
  74. 74.
    Rauch PJG, de Vos WM. Identification and characterization of genes involved in excision of the Lactococcus lactis conjugative transposon Tn5276. J Bacteriol 1994; 176: 2165–2171.PubMedGoogle Scholar
  75. 75.
    Rauch PJG, Beerthuyzen MM, de Vos WM. Distribution and evolution of nisin sucrose elements in Lactococcus lactis. Appl Environ Microbiol 1994; 60: 1798–1804.PubMedGoogle Scholar
  76. 76.
    Moschetti G, Villani F, Blaiotta G et al. Presence of non-functional nisin genes in Lactococcus lactis subsp. lactis isolated from natural starters. FEMS Microbiol Lett 1996; 145: 27–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Kuipers OP, Beerthuyzen MM, de Ruyter PGGA et al. Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J Biol Chem 1995; 270: 27299–27304.PubMedCrossRefGoogle Scholar
  78. 78.
    De Ruyter PGGA, Kuipers OP, Beerthuyzen MM et al. Functional analysis of promoters in the nisin gene cluster of Lactococcus lactis. J Bacteriol 1996; 178: 3434–3439.PubMedGoogle Scholar
  79. 79.
    Qiao M, Ye S, Koponen O et al. Regulation of the nisin operons in Lactococcus lactis N8. J Appl Bacteriol 1996; 80: 626–634.PubMedCrossRefGoogle Scholar
  80. 80.
    Liu W, Hansen JN. Conversion of Bacillus subtilis 168 to a subtilin producer by competence transformation. J Bacteriol 1991; 173: 7387–7390.PubMedGoogle Scholar
  81. 81.
    Schnell N, Engelke G, Augustin J et al. The operon-like organisation of lantibiotic epidermin biosynthesis genes. In: Jung G, Sahl H-G eds. Nisin and Novel Lantibiotics. Leiden: ESCOM, 1991: 269–276.Google Scholar
  82. 82.
    Augustin J, Rosenstein R, Wieland B et al. Genetic analysis of epidermin biosynthetic genes and epidermin-negative mutants of Staphylococcus epidermidis. Eur J Biochem 1992; 204: 1149–1154.PubMedCrossRefGoogle Scholar
  83. 83.
    Augustin J, Rosenstein R, Kupke T et al. Identification of epidermin biosynthetic genes by complementation studies and heterologous expression. In Jung G, Sahl H-G eds. Nisin and novel lantibiotics. Leiden: ESCOM, 1991: 277–286.Google Scholar
  84. 84.
    Peschel A, Augustin J, Kupke T et al. Regulation of epidermin biosynthetic genes by EpiQ. Mol Microbiol 1993; 9: 31–39.PubMedCrossRefGoogle Scholar
  85. 85.
    Ersfeld-Dreßen H, Sahl H-G, Brandis H. Plasmid involvement in production of and immunity to the staphylococcin-like peptide Pep5. J Gen Microbiol 1984; 130: 3029–3035.PubMedGoogle Scholar
  86. 86.
    Bierbaum G, Reis M, Szekat C et al. Construction of an expression system for engineering of the lantibiotic Peps. Appl Environ Microbiol 1994; 60: 4332–4338.Google Scholar
  87. 87.
    Neis S, Bierbaum G, Josten M et al. Effect of leader peptide mutations on biosynthesis of the lantibiotic Pep5. FEMS Microbiol Lett 1997; 149: 249–255.Google Scholar
  88. 88.
    Dyke KGH, Rowland S-J. The 13-lactamase transposon TnS52. In: Novick RP ed. Molecular Biology of the Staphylococci. New York: VCH Publishers Inc., 1990: 147–164.Google Scholar
  89. 89.
    Tagg JR, Skjold SA. A bacteriocin produced by certain M-type 49 Streptococcus pyogenes strains when incubated anaerobically. J Hyg 1984; 92: 339–344.CrossRefGoogle Scholar
  90. 90.
    Simpson WJ, Ragland NL, Ronson CW et al. A lantibiotic gene family widely distributed in Streptococcus salivarius and Streptococcus pyogenes. Dev Biol Stand 1995; 85: 639–643.PubMedGoogle Scholar
  91. 91.
    Segarra RA, Booth MC, Morales DA et al. Molecular characterization of the Enterococcus faecalis cytolysin activator. Infect Immun 1991; 59: 1239–1246.PubMedGoogle Scholar
  92. 92.
    Booth MC, Bogie CP, Sahl HG et al. Structural analysis and proteolytic activation of Enterococcus faecalis cytolysin, a novel lantibiotic. Mol Microbiol 1996; 21: 1175–1184.PubMedCrossRefGoogle Scholar
  93. 93.
    Martvedt CI, Nes IF. Plasmid-associated bacteriocin production by a Lactobacillus sake strain. J Gen Microbiol 1990; 136: 1601–1607.Google Scholar
  94. 94.
    Rodriguez-Skinz MC, Hernandez-Chico C, Moreno F. Molecular characterization of pmbA, an Escherichia coli chromosomal gene required for the production of the antibiotic peptide MccB17. Mol Microbiol 1990; 41921–1932.Google Scholar
  95. 95.
    Moreno F, San Milln JL, Castillo I et al. Escherichia coli genes regulating the production of microcins MccB17 and Mccc7. In: James R, Lazdunski C, Pattus F, eds. Bacteriocins, Microcins and Lantibiotics. Berlin: Springer, 1992: 3–14.CrossRefGoogle Scholar
  96. 96.
    Hynes WL, Ferretti JJ. A response regulator gene controls production of the lantibiotic streptococcin A-FF22. Dev Biol Stand 1995; 85635–637.Google Scholar
  97. 97.
    Dodd HM, Horn N, Chan WC et al. Molecular analysis of the regulation of nisin immunity. Microbiology 1996; 142:2385–2392.Google Scholar
  98. 98.
    Hurst A. Biosynthesis of the antibiotic nisin and other basic peptides by Streptococcus lactis grown in batch culture. J Gen Microbiol 1966; 45: 503–513.Google Scholar
  99. 99.
    De Ruyter PGGA, Kuipers OP, de Vos WM. Controlled gene expression systems for Lactococcus lactis with the food-grade inducer nisin. Appl Environ Microbiol 1996; 62: 3662–3667.PubMedGoogle Scholar
  100. 100.
    Ra SR, Qiao M, Immonen T et al. Genes responsible for nisin synthesis, regulation and immunity form a regulon of two operons and are induced by nisin in Lactococcus lactis N8. Microbiology 1996; 142: 1281–1288.PubMedCrossRefGoogle Scholar
  101. 101.
    Diep DB, Hävarstein LS, Nes IF. Characterization of the locus responsible for the bacteriocin production in Lactobacillus plantarum Cu. J Bacteriol 1996; 178: 4472–4483.PubMedGoogle Scholar
  102. 102.
    Eijsink VGH, Brurberg MB, Middelhoven PH et al. Induction of bacteriocin production in Lactobacillus sake by a secreted peptide. J Bacteriol 1996; 178: 2232–2237.PubMedGoogle Scholar
  103. 103.
    Diep DB, Hävarstein LS, Nissen-Meyer J et al. The gene encoding plantaricin A, a bacteriocin from Lactobacillus plantarum Cu, is located on the same transcription unit as an agr-like regulatory system. Appl Environ Microbiol 1994; 60: 160–166.PubMedGoogle Scholar
  104. 104.
    Magnuson R, Solomon J, Grossman AD. Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell 1994; 77: 207–216.PubMedCrossRefGoogle Scholar
  105. 105.
    Ji G, Beavis RC, Novick RP. Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. Proc Natl Acad Sci USA 1995; 92: 12055–12059.PubMedCrossRefGoogle Scholar
  106. 106.
    Van der Meer JR, Rollema HS, Siezen RJ et al. Influence of amino acid substitutions in the nisin leader peptide on biosynthesis and secretion of nisin by Lactococcus lactis. J Biol Chem 1994; 269: 3555–3562.PubMedGoogle Scholar
  107. 107.
    Kupke T, Stevanovie S, Ottenwälder B et al. Purification and characterization of EpiA, the peptide substrate for post-translational modifications involved in epidermin biosynthesis. FEMS Microbiol Lett 1993; 112: 43–48.PubMedCrossRefGoogle Scholar
  108. 108.
    Beck-Sickinger AG, Jung G. Synthesis and conformational analysis of lantibiotic leader-, pro-and pre-peptides. In: Jung G, Sahl H-G eds. Nisin and Novel Lantibiotics. Leiden: ESCOM, 1991: 218–230.Google Scholar
  109. 109.
    Pugsley AP. The complete general secretory pathway in Gram-negative bacteria. Microbiol Rev 1993; 57: 50–108.PubMedGoogle Scholar
  110. no. Sahl H-G. Pore formation in bacterial membranes by cationic lantibiotics. In: Jung G, Sahl H-G eds. Nisin and Novel Lantibiotics. Leiden: ESCOM, 1991: 347–358.Google Scholar
  111. 111.
    Freund S, Jung G. Lantibiotics: an overview and conformational studies on gallidermin and Peps. In: James R, Lazdunski C, Pattus F, eds. Bacteriocins, Microcins and Lantibiotics. Berlin: Springer, 1992: 75–92.CrossRefGoogle Scholar
  112. 112.
    Surovoy A, Waidelich D, Jung G. Electrospray mass spectroscopic analysis of metal-peptide complexes. In: Schneider C, Eberle AN eds. Proceedings of the 22nd European peptide symposium, Peptides 1992. Leiden: ESCOM, 1992: 563–564.Google Scholar
  113. 113.
    Kuipers OP, Rollema HS, de Vos WM et al. Biosynthesis and secretion of a precursor of nisin Z by Lactococcus lactis, directed by the leader peptide of the homologous lantibiotic subtilin from Bacillus subtilis. FEBS Letters 1993; 33023–27.Google Scholar
  114. 114.
    Rintala H, Graeffe T, Paulin L et al. Biosynthesis of nisin in the subtilin producer Bacillus subtilis ATCC6633. Biotechnol Lett 1993; 15: 991–996.CrossRefGoogle Scholar
  115. 115.
    Chakicherla A, Hansen JN. Role of the leader and structural regions of prelantibiotic peptides as assessed by expressing nisin-subtilin chimeras in Bacillus subtilis 168, and characterization of their physical, chemical, and antimicrobial properties. J Biol Chem 1995; 270: 23533–23539.PubMedCrossRefGoogle Scholar
  116. 116.
    Yorgey P, Davagnino J, Kolter R. The maturation pathway of microcin B17, a peptide inhibitor of DNA gyrase. Mol Microbiol 1993; 9: 897–905.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Ralph W. Jack
    • 1
    • 2
  • Gabriele Bierbaum
    • 3
  • Hans-Georg Sahl
    • 3
  1. 1.Institute for Organic ChemistryUniversity of TübingenTübingenGermany
  2. 2.ECHAZ microcollectionsReutlingenGermany
  3. 3.Institute for Medical Microbiology and ImmunologyUniversity of BonnBonnGermany

Personalised recommendations