Rationale Strategien zur Isolierung bakterieller Lassopeptide - Struktur, Biosynthese und Anwendungspotential

Bakterielle Lassopeptide sind ribosomal synthetisierte, bioaktive Peptide, die sich aus 16 bis 21 proteinogenen Aminosäuren zusammensetzen. Sie zeichnen sich durch eine verzweigt-zyklische Primärstruktur aus, die durch einen N-terminalen Makrolaktamring und einen linearen C-Terminus charakterisiert...

Full description

Saved in:
Bibliographic Details
Main Author: Knappe, Thomas
Contributors: Marahiel, Mohamed A. (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2011
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!

1. Gillon, A.D., Saska, I., Jennings, C.V., Guarino, R.F., Craik, D.J. and Anderson, M.A. (2008). Biosynthesis of circular proteins in plants. Plant J 53, 505‐15. [78]

2. Saska, I., Gillon, A.D., Hatsugai, N., Dietzgen, R.G., Hara‐Nishimura, I., Anderson, M.A. and Craik, D.J. (2007). An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem 282, 29721‐8. [77]

3. Herrmann, T., Guntert, P. and Wuthrich, K. (2002). Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA. Journal of Molecular Biology 319, 209‐227.

4. Newman, D.J. and Cragg, G.M. (2007). Natural products as sources of new drugs over the last 25 years.

5. Fox, J.D., Routzahn, K.M., Bucher, M.H. and Waugh, D.S. (2003). Maltodextrin‐binding proteins from diverse bacteria and archaea are potent solubility enhancers. FEBS Lett 537, 53‐7.

6. Larsen, T.M., Boehlein, S.K., Schuster, S.M., Richards, N.G., Thoden, J.B., Holden, H.M. and Rayment, I. (1999). Three‐dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry 38, 16146‐57.

7. Adelman, K. et al. (2004). Molecular mechanism of transcription inhibition by peptide antibiotic Microcin J25. Mol Cell 14, 753‐62.

8. Sturme, M.H., Kleerebezem, M., Nakayama, J., Akkermans, A.D., Vaugha, E.E. and de Vos, W.M. (2002). Cell to cell communication by autoinducing peptides in gram‐positive bacteria. Antonie Van Leeuwenhoek 81, 233‐43. [39]

9. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. and Lipman, D.J. (1990). Basic local alignment search tool. J Mol Biol 215, 403‐10.

10. Craik, D.J., Mylne, J.S. and Daly, N.L. (2010). Cyclotides: macrocyclic peptides with applications in drug design and agriculture. Cell Mol Life Sci 67, 9‐16. [31]

11. Bennett, J. and Scott, K.J. (1971). Quantitative staining of fraction I protein in polyacrylamide gels using Coomassie brillant blue. Anal Biochem 43, 173‐82.

12. Silkin, L., Hamza, S., Kaufman, S., Cobb, S.L. and Vederas, J.C. (2008). Spermicidal bacteriocins: lacticin 3147 and subtilosin A. Bioorg Med Chem Lett 18, 3103‐6. [61]

13. Membrane permeabilization, orientation, and antimicrobial mechanism of subtilosin A. Chem Phys Lipids 137, 38‐51. [60]

14. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A. (2005). Biotin synthase mechanism: an overview. Biochem Soc Trans 33, 820‐3. [55]

15. Shelburne, C.E., An, F.Y., Dholpe, V., Ramamoorthy, A., Lopatin, D.E. and Lantz, M.S. (2007). The spectrum of antimicrobial activity of the bacteriocin subtilosin A. J Antimicrob Chemother 59, 297‐300. [59] Thennarasu, S., Lee, D.K., Poon, A., Kawulka, K.E., Vederas, J.C. and Ramamoorthy, A. (2005).

16. Bryson, K., McGuffin, L.J., Marsden, R.L., Ward, J.J., Sodhi, J.S. and Jones, D.T. (2005). Protein structure prediction servers at University College London. Nucleic Acids Res 33, W36‐8.

17. Caboche, S., Pupin, M., Leclere, V., Fontaine, A., Jacques, P. and Kucherov, G. (2008). NORINE: a database of nonribosomal peptides. Nucleic Acids Res 36, D326‐31. [23]

18. Wang, C.K., Kaas, Q., Chiche, L. and Craik, D.J. (2008). CyBase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering. Nucleic Acids Res 36, D206‐10. [75]

19. In, Y., Doi, M., Inoue, M., Ishida, T., Hamada, Y. and Shioiri, T. (1994). Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella. Acta Crystallogr C 50 ( Pt 3), 432‐4. [42]

20. Craik, D.J., Clark, R.J. and Daly, N.L. (2007). Potential therapeutic applications of the cyclotides and related cystine knot mini‐proteins. Expert Opin Investig Drugs 16, 595‐604. [82]

21. Huang, Y.H., Colgrave, M.L., Daly, N.L., Keleshian, A., Martinac, B. and Craik, D.J. (2009). The biological activity of the prototypic cyclotide kalata b1 is modulated by the formation of multimeric pores. J Biol Chem 284, 20699‐707. [83]

22. Craik, D.J. (2009). Circling the enemy: cyclic proteins in plant defence. Trends Plant Sci 14, 328‐35. [35]

23. Daly, N.L., Rosengren, K.J. and Craik, D.J. (2009). Discovery, structure and biological activities of cyclotides. Adv Drug Deliv Rev 61, 918‐30. [74]

24. Rosengren, K.J., Blond, A., Afonso, C., Tabet, J.C., Rebuffat, S. and Craik, D.J. (2004). Structure of thermolysin cleaved microcin J25: extreme stability of a two‐chain antimicrobial peptide devoid of covalent links. Biochemistry 43, 4696‐702.

25. The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chem Biol 14, 53‐63. [15]

26. Lehrer, R.I. and Ganz, T. (2002). Defensins of vertebrate animals. Curr Opin Immunol 14, 96‐102. [32]

27. Minniti, G., Muni, R., Lanzetta, G., Marchetti, P. and Enrici, R.M. (2009). Chemotherapy for glioblastoma: current treatment and future perspectives for cytotoxic and targeted agents. Anticancer Res 29, 5171‐84. Danksagung 138

28. De Marco, V., Stier, G., Blandin, S. and de Marco, A. (2004). The solubility and stability of recombinant proteins are increased by their fusion to NusA. Biochem Biophys Res Commun 322, 766‐71.

29. Duerkop, B.A. et al. (2009). Quorum‐sensing control of antibiotic synthesis in Burkholderia thailandensis. J Bacteriol 191, 3909‐18.

30. Babasaki, K., Takao, T., Shimonishi, Y. and Kurahashi, K. (1985). Subtilosin A, a new antibiotic peptide produced by Bacillus subtilis 168: isolation, structural analysis, and biogenesis. J Biochem 98, 585‐603. [53]

31. Potterat, O., Stephan, H., Metzger, J.W., Gnau, V., Zähner, H. and Jung, G. (1994). Aborycin ‐ A Tricyclic 21‐Peptide Antibiotic Isolated from Streptomyces griseoflavus. Liebigs Annalen der Chemie 1994, 741‐ 743.

32. Weber, W., Fischli, W., Hochuli, E., Kupfer, E. and Weibel, E.K. (1991). Anantin‐‐a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity.

33. Gruber, C.W., Cemazar, M., Clark, R.J., Horibe, T., Renda, R.F., Anderson, M.A. and Craik, D.J. (2007). A novel plant protein‐disulfide isomerase involved in the oxidative folding of cystine knot defense proteins. J Biol Chem 282, 20435‐46. [80]

34. Demain, A.L. (2009). Antibiotics: natural products essential to human health. Med Res Rev 29, 821‐42. [5] Singh, S.B. and Barrett, J.F. (2006). Empirical antibacterial drug discovery‐‐foundation in natural products. Biochem Pharmacol 71, 1006‐15. [6]

35. Ireland, C.M., Durso, A.R., Newman, R.A. and Hacker, M.P. (1982). Antineoplastic cyclic peptides from the marine tunicate Lissoclinum patella. The Journal of Organic Chemistry 47, 1807‐1811. [65]

36. Laskowski, R.A., Rullmann, J.A.C., MacArthur, M.W., Kaptein, R. and Thornton, J.M. (1996). AQUA and PROCHECK‐NMR: Programs for checking the quality of protein structures solved by NMR. Journal of Biomolecular Nmr 8, 477‐486.

37. Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‐dye binding. Anal Biochem 72, 248‐54.

38. Richards, N.G. and Kilberg, M.S. (2006). Asparagine synthetase chemotherapy. Annu Rev Biochem 75, 629‐54.

39. Guntert, P., Braun, W., Billeter, M. and Wuthrich, K. (1989). Automated Stereospecific H‐1‐Nmr Assignments and Their Impact on the Precision of Protein‐Structure Determinations in Solution. Journal of the American Chemical Society 111, 3997‐4004.

40. Phillips, R. (2005). Back to the past: new drugs from ancient molecules? Nat Immunol 6, 963‐4. [96]

41. Potterat, O., Wagner, K., Gemmecker, G., Mack, J., Puder, C., Vettermann, R. and Streicher, R. (2004). BI‐32169, a bicyclic 19‐peptide with strong glucagon receptor antagonist activity from Streptomyces sp. J Nat Prod 67, 1528‐31.

42. Potterat, O., Streicher, R., Wagner, K., Maurer, T., Mack, J. and Peters, S. (2004). Bicyclic oligopeptides. Patent US 7101848.

43. Bode, H.B., Bethe, B., Hofs, R. and Zeeck, A. (2002). Big effects from small changes: possible ways to explore nature's chemical diversity. Chembiochem 3, 619‐27. [13]

44. Gruber, C.W., Cemazar, M., Mechler, A., Martin, L.L. and Craik, D.J. (2009). Biochemical and biophysical characterization of a novel plant protein disulfide isomerase. Biopolymers 92, 35‐43. [81]

45. Mahenthiralingam, E., Baldwin, A. and Dowson, C.G. (2008). Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol [205] Lipuma, J.J. (2005). Update on the Burkholderia cepacia complex. Curr Opin Pulm Med 11, 528‐33.

46. Brett, P.J., DeShazer, D. and Woods, D.E. (1998). Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei‐like species. Int J Syst Bacteriol 48 Pt 1, 317‐20.

47. Gill, S.C. and von Hippel, P.H. (1989). Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem 182, 319‐26.

48. Leikina, E. et al. (2005). Carbohydrate‐binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nat Immunol 6, 995‐1001. [94] Venkataraman, N., Cole, A.L., Ruchala, P., Waring, A.J., Lehrer, R.I., Stuchlik, O., Pohl, J. and Cole, A.M. (2009). Reawakening retrocyclins: ancestral human defensins active against HIV‐1. PLoS Biol 7, e95. [95]

49. Schmidt, E.W. and Donia, M.S. (2009). Chapter 23. Cyanobactin ribosomally synthesized peptides‐‐a case of deep metagenome mining. Methods Enzymol 458, 575‐96. [27]

50. Galvez, A., Maqueda, M., Valdivia, E., Quesada, A. and Montoya, E. (1986). Characterization and partial purification of a broad spectrum antibiotic AS‐48 produced by Streptococcus faecalis. Can J Microbiol 32, 765‐71. [46] Kalmokoff, M.L. and Teather, R.M. (1997). Isolation and characterization of a bacteriocin (Butyrivibriocin AR10) from the ruminal anaerobe Butyrivibrio fibrisolvens AR10: evidence in support of the widespread occurrence of bacteriocin‐like activity among ruminal isolates of B. fibrisolvens. Appl Environ Microbiol 63, 394‐402. [47] Martin‐Visscher, L.A., van Belkum, M.J., Garneau‐Tsodikova, S., Whittal, R.M., Zheng, J., McMullen, L.M. and Vederas, J.C. (2008). Isolation and characterization of carnocyclin a, a novel circular bacteriocin produced by Carnobacterium maltaromaticum UAL307. Appl Environ Microbiol 74, 4756‐ 63. [48]

51. Trabi, M. and Craik, D.J. (2002). Circular proteins‐‐no end in sight. Trends Biochem Sci 27, 132‐8. [43]

52. Breci, L.A., Tabb, D.L., Yates, J.R., 3rd and Wysocki, V.H. (2003). Cleavage N‐terminal to proline: analysis of a database of peptide tandem mass spectra. Anal Chem 75, 1963‐71.

53. Challis, G.L. and Ravel, J. (2000). Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non‐ribosomal peptide synthetase. FEMS Microbiol Lett 187, 111‐4. [17]

54. Marblestone, J.G., Edavettal, S.C., Lim, Y., Lim, P., Zuo, X. and Butt, T.R. (2006). Comparison of SUMO fusion technology with traditional gene fusion systems: enhanced expression and solubility with SUMO. Protein Sci 15, 182‐9.

55. Dutton, J.L., Renda, R.F., Waine, C., Clark, R.J., Daly, N.L., Jennings, C.V., Anderson, M.A. and Craik, D.J. (2004). Conserved structural and sequence elements implicated in the processing of gene‐encoded circular proteins. J Biol Chem 279, 46858‐67. [76]

56. Martin, J.F. and Demain, A.L. (1980). Control of antibiotic biosynthesis. Microbiol Rev 44, 230‐51.

57. George, A.M., Jones, P.M. and Middleton, P.G. (2009). Cystic fibrosis infections: treatment strategies and prospects. FEMS Microbiol Lett 300, 153‐64.

58. Der größte Dank gilt meinen Eltern und meiner Schwester Daniela, die mich im Laufe meines Lebens in jeder Hinsicht unterstützt haben. Ohne diesen Rückhalt wären mein Studium und auch die Doktorarbeit nicht in dieser Form möglich gewesen.

59. Marugan, J.J. et al. (2005). Design, synthesis, and biological evaluation of novel potent and selective alphavbeta3/alphavbeta5 integrin dual inhibitors with improved bioavailability. Selection of the molecular core. J Med Chem 48, 926‐34.

60. Discovery and in vitro biosynthesis of haloduracin, a two‐component lantibiotic. Proc Natl Acad Sci U S A 103, 17243‐8. [16]

61. Lautru, S., Deeth, R.J., Bailey, L.M. and Challis, G.L. (2005). Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat Chem Biol 1, 265‐9. [18] Nolan, E.M. and Walsh, C.T. (2009). How nature morphs peptide scaffolds into antibiotics. Chembiochem 10, 34‐53. [19] McIntosh, J.A., Donia, M.S. and Schmidt, E.W. (2009). Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat Prod Rep 26, 537‐59. [20]

62. Pan, S.J., Cheung, W.L. and Link, A.J. (2010). Engineered gene clusters for the production of the antimicrobial peptide microcin J25. Protein Expr Purif 71, 200‐6.

63. Nygren, P.A., Stahl, S. and Uhlen, M. (1994). Engineering proteins to facilitate bioprocessing. Trends Biotechnol 12, 184‐8.

64. Oman, T.J. and van der Donk, W.A. (2010). Follow the leader: the use of leader peptides to guide natural product biosynthesis. Nat Chem Biol 6, 9‐18. [24]

65. Bulaj, G. (2005). Formation of disulfide bonds in proteins and peptides. Biotechnol Adv 23, 87‐92. [29] Bulaj, G. and Olivera, B.M. (2008). Folding of conotoxins: formation of the native disulfide bridges during chemical synthesis and biosynthesis of Conus peptides. Antioxid Redox Signal 10, 141‐55. [30]

66. Li, Y.M., Milne, J.C., Madison, L.L., Kolter, R. and Walsh, C.T. (1996). From peptide precursors to oxazole and thiazole‐containing peptide antibiotics: microcin B17 synthase. Science 274, 1188‐93.

67. Kawai, Y., Saito, T., Kitazawa, H. and Itoh, T. (1998). Gassericin A; an uncommon cyclic bacteriocin produced by Lactobacillus gasseri LA39 linked at N‐ and C‐terminal ends. Biosci Biotechnol Biochem 62, 2438‐40. [50]

68. Maqueda, M., Sanchez‐Hidalgo, M., Fernandez, M., Montalban‐Lopez, M., Valdivia, E. and Martinez‐ Bueno, M. (2008). Genetic features of circular bacteriocins produced by Gram‐positive bacteria. FEMS Microbiol Rev 32, 2‐22. [34]

69. Whitlock, G.C., Estes, D.M. and Torres, A.G. (2007). Glanders: off to the races with Burkholderia mallei. FEMS Microbiol Lett 277, 115‐22.

70. Krause, S., Schmoldt, H.U., Wentzel, A., Ballmaier, M., Friedrich, K. and Kolmar, H. (2007). Grafting of thrombopoietin‐mimetic peptides into cystine knot miniproteins yields high‐affinity thrombopoietin antagonists and agonists. FEBS J 274, 86‐95.

71. Constantine, K.L. et al. (1995). High‐resolution solution structure of siamycin II: novel amphipathic character of a 21‐residue peptide that inhibits HIV fusion. J Biomol NMR 5, 271‐86.

72. HPLC purification and re‐evaluation of chemical identity of two circular bacteriocins, gassericin A and reutericin 6. Lett Appl Microbiol [54]

73. Kemperman, R., Kuipers, A., Karsens, H., Nauta, A., Kuipers, O. and Kok, J. (2003). Identification and characterization of two novel clostridial bacteriocins, circularin A and closticin 574. Appl Environ Microbiol 69, 1589‐97. [49]

74. Zhaofei, L., Fan, W. and Xiaoyuan, C. (2008). Integrin alpha(V)beta(3)‐targeted cancer therapy. Drug Development Research 69, 329‐339.

75. Stupp, R. and Ruegg, C. (2007). Integrin inhibitors reaching the clinic. J Clin Oncol 25, 1637‐8.

76. Hynes, R.O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673‐87.

77. Jin, H. and Varner, J. (2004). Integrins: roles in cancer development and as treatment targets. Br J Cancer 90, 561‐5.

78. Helynck, G., Dubertret, C., Mayaux, J.F. and Leboul, J. (1993). Isolation of RP 71955, a new anti‐HIV‐1 peptide secondary metabolite. J Antibiot (Tokyo) 46, 1756‐7.

79. Isolation, structural determination and biological properties of MS‐271. Bioorg Med Chem 4, 115‐20.

80. Willey, J.M. and van der Donk, W.A. (2007). Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol 61, 477‐501. [25] Yorgey, P., Lee, J., Kordel, J., Vivas, E., Warner, P., Jebaratnam, D. and Kolter, R. (1994).

81. Iwatsuki, M., Tomoda, H., Uchida, R., Gouda, H., Hirono, S. and Omura, S. (2006). Lariatins, antimycobacterial peptides produced by Rhodococcus sp. K01‐B0171, have a lasso structure. J Am Chem Soc 128, 7486‐91.

82. Iwatsuki, M. et al. (2007). Lariatins, novel anti‐mycobacterial peptides with a lasso structure, produced by Rhodococcus jostii K01‐B0171. J Antibiot (Tokyo) 60, 357‐63.

83. Iwatsuki, M., Koizumi, Y., Gouda, H., Hirono, S., Tomoda, H. and Omura, S. (2009). Lys17 in the 'lasso' peptide lariatin A is responsible for anti‐mycobacterial activity. Bioorg Med Chem Lett 19, 2888‐90.

84. Fox, J.D. and Waugh, D.S. (2003). Maltose‐binding protein as a solubility enhancer. Methods Mol Biol 205, 99‐117.

85. Rosengren, K.J., Clark, R.J., Daly, N.L., Goransson, U., Jones, A. and Craik, D.J. (2003). Microcin J25 has a threaded sidechain‐to‐backbone ring structure and not a head‐to‐tail cyclized backbone. J Am Chem Soc 125, 12464‐74.

86. Wilkinson, B. and Micklefield, J. (2007). Mining and engineering natural‐product biosynthetic pathways. Nat Chem Biol 3, 379‐86.

87. Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989). Molecular cloning: a laboratory manual. Cold Spring Laboratory press, Cold spring Harbor, NY [158] Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680‐5.

88. Sieber, S.A. and Marahiel, M.A. (2005). Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chem Rev 105, 715‐38. [21]

89. Katahira, R., Yamasaki, M., Matsuda, Y. and Yoshida, M. (1996). MS‐271, a novel inhibitor of calmodulin‐activated myosin light chain kinase from Streptomyces sp.‐‐II. Solution structure of MS‐ 271: characteristic features of the "lasso' structure. Bioorg Med Chem 4, 121‐9. [99]

90. Yuzenkova, J. et al. (2002). Mutations of bacterial RNA polymerase leading to resistance to microcin j25. J Biol Chem 277, 50867‐75.

91. Donia, M.S., Hathaway, B.J., Sudek, S., Haygood, M.G., Rosovitz, M.J., Ravel, J. and Schmidt, E.W. (2006). Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nat Chem Biol 2, 729‐35. [69]

92. Corre, C. and Challis, G.L. (2009). New natural product biosynthetic chemistry discovered by genome mining. Nat Prod Rep 26, 977‐86. [9] Zerikly, M. and Challis, G.L. (2009). Strategies for the discovery of new natural products by genome mining. Chembiochem 10, 625‐33. [10] Bentley, S.D. et al. (2002). Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417, 141‐7. [11] Scherlach, K. and Hertweck, C. (2009). Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7, 1753‐60. [12]

93. Dechantsreiter, M.A., Planker, E., Matha, B., Lohof, E., Holzemann, G., Jonczyk, A., Goodman, S.L. and Kessler, H. (1999). N‐Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem 42, 3033‐40.

94. Wagner, G. (1990). Nmr Investigations of Protein‐Structure. Progress in Nuclear Magnetic Resonance Spectroscopy 22, 101‐139.

95. Novel propeptin analog, propeptin‐2, missing two amino acid residues from the propeptin C‐terminus loses antibiotic potency. J Antibiot (Tokyo) 60, 519‐23.

96. McCormack, J.G., Westergaard, N., Kristiansen, M., Brand, C.L. and Lau, J. (2001). Pharmacological approaches to inhibit endogenous glucose production as a means of anti‐diabetic therapy. Curr Pharm Des 7, 1451‐74.

97. Hoffmann, J.A., Kafatos, F.C., Janeway, C.A. and Ezekowitz, R.A. (1999). Phylogenetic perspectives in innate immunity. Science 284, 1313‐8. [86]

98. Donadio, S., Monciardini, P. and Sosio, M. (2007). Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics. Nat Prod Rep 24, 1073‐109. [8]

99. Philmus, B., Christiansen, G., Yoshida, W.Y. and Hemscheidt, T.K. (2008). Post‐translational modification in microviridin biosynthesis. Chembiochem 9, 3066‐73. [40]

100. Posttranslational modifications in microcin B17 define an additional class of DNA gyrase inhibitor. Proc Natl Acad Sci U S A 91, 4519‐23. [26]

101. Selsted, M.E., Brown, D.M., DeLange, R.J., Harwig, S.S. and Lehrer, R.I. (1985). Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils. J Biol Chem 260, 4579‐84. [87] Diamond, G., Zasloff, M., Eck, H., Brasseur, M., Maloy, W.L. and Bevins, C.L. (1991). Tracheal antimicrobial peptide, a cysteine‐rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A 88, 3952‐6. [88] Tang, Y.Q., Yuan, J., Osapay, G., Osapay, K., Tran, D., Miller, C.J., Ouellette, A.J. and Selsted, M.E. (1999). A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha‐defensins. Science 286, 498‐502. [89] Nguyen, T.X., Cole, A.M. and Lehrer, R.I. (2003). Evolution of primate theta‐defensins: a serpentine path to a sweet tooth. Peptides 24, 1647‐54. [90]

102. Patellamide A and C biosynthesis by a microcin‐like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella. Proc Natl Acad Sci U S A 102, 7315‐20. [66] Lee, J., McIntosh, J., Hathaway, B.J. and Schmidt, E.W. (2009). Using marine natural products to discover a protease that catalyzes peptide macrocyclization of diverse substrates. J Am Chem Soc 131, 2122‐4. [67]

103. Schein, C.H. (1989). Production of Soluble Recombinant Proteins in Bacteria. Nat Biotech 7, 1141‐1149.

104. Kabuki, T., Saito, T., Kawai, Y., Uemura, J. and Itoh, T. (1997). Production, purification and characterization of reutericin 6, a bacteriocin with lytic activity produced by Lactobacillus reuteri LA6. Int J Food Microbiol 34, 145‐56. [51]

105. Kuliopulos, A. and Walsh, C.T. (1994). Production, Purification, and Cleavage of Tandem Repeats of Recombinant Peptides. Journal of the American Chemical Society 116, 4599‐4607.

106. Kimura, K., Kanou, F., Takahashi, H., Esumi, Y., Uramoto, M. and Yoshihama, M. (1997). Propeptin, a new inhibitor of prolyl endopeptidase produced by Microbispora. I. Fermentation, isolation and biological properties. J Antibiot (Tokyo) 50, 373‐8.

107. Bordusa, F. (2002). Proteases in organic synthesis. Chem Rev 102, 4817‐68. [58]

108. Gruber, C.W., Cemazar, M., Heras, B., Martin, J.L. and Craik, D.J. (2006). Protein disulfide isomerase: the structure of oxidative folding. Trends Biochem Sci 31, 455‐64. [79]

109. Bamburg, J.R. (1999). Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15, 185‐230. [72]

110. Marion, D., Ikura, M., Tschudin, R. and Bax, A. (1989). Rapid Recording of 2D NMR Spectra without Phase Cycling. Application to the Study of Hydrogen Exchange in Proteins. J. Magn. Reson. 85, 393‐ 399.

111. Morishita, Y. et al. (1994). RES‐701‐1, a novel and selective endothelin type B receptor antagonist produced by Streptomyces sp. RE‐701. I. Characterization of producing strain, fermentation, isolation, physico‐chemical and biological properties. J Antibiot (Tokyo) 47, 269‐75.

112. McGowan, J.E., Jr. (2006). Resistance in nonfermenting gram‐negative bacteria: multidrug resistance to the maximum. Am J Infect Control 34, S29‐37; discussion S64‐73.

113. Daly, N.L. et al. (2007). Retrocyclin‐2: structural analysis of a potent anti‐HIV theta‐defensin. Biochemistry 46, 9920‐8. [97]

114. Cole, A.M., Wang, W., Waring, A.J. and Lehrer, R.I. (2004). Retrocyclins: using past as prologue. Curr Protein Pept Sci 5, 373‐81. [91]

115. Wang, S.C. and Frey, P.A. (2007). S‐adenosylmethionine as an oxidant: the radical SAM superfamily. Trends Biochem Sci 32, 101‐10. [56]

116. Detlefsen, D.J. et al. (1995). Siamycins I and II, new anti‐HIV‐1 peptides: II. Sequence analysis and structure determination of siamycin I. J Antibiot (Tokyo) 48, 1515‐7.

117. Tsunakawa, M. et al. (1995). Siamycins I and II, new anti‐HIV peptides: I. Fermentation, isolation, biological activity and initial characterization. J Antibiot (Tokyo) 48, 433‐4.

118. Scholz, C., Eckert, B., Hagn, F., Schaarschmidt, P., Balbach, J. and Schmid, F.X. (2006). SlyD proteins from different species exhibit high prolyl isomerase and chaperone activities. Biochemistry 45, 20‐33.

119. Katahira, R., Shibata, K., Yamasaki, M., Matsuda, Y. and Yoshida, M. (1995). Solution structure of endothelin B receptor selective antagonist RES‐701‐1 determined by 1H NMR spectroscopy. Bioorg Med Chem 3, 1273‐80. [98]

120. Blond, A. et al. (2001). Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli. Eur J Biochem 268, 2124‐33.

121. Frechet, D. et al. (1994). Solution structure of RP 71955, a new 21 amino acid tricyclic peptide active against HIV‐1 virus. Biochemistry 33, 42‐50.

122. Milne, B.F., Long, P.F., Starcevic, A., Hranueli, D. and Jaspars, M. (2006). Spontaneity in the patellamide biosynthetic pathway. Org Biomol Chem 4, 631‐8. [68]

123. Bushnell, D.A., Cramer, P. and Kornberg, R.D. (2002). Structural basis of transcription: alpha‐amanitin‐ RNA polymerase II cocrystal at 2.8 A resolution. Proc Natl Acad Sci U S A 99, 1218‐22. [71]

124. Koronakis, V., Eswaran, J. and Hughes, C. (2004). Structure and function of TolC: the bacterial exit duct for proteins and drugs. Annu Rev Biochem 73, 467‐89.

125. Bayro, M.J. et al. (2003). Structure of antibacterial peptide microcin J25: a 21‐residue lariat protoknot. J Am Chem Soc 125, 12382‐3.

126. Miller, M.T., Bachmann, B.O., Townsend, C.A. and Rosenzweig, A.C. (2001). Structure of beta‐lactam synthetase reveals how to synthesize antibiotics instead of asparagine. Nat Struct Biol 8, 684‐9.

127. Structure of subtilosin A, an antimicrobial peptide from Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to alpha‐carbons of phenylalanine and threonine. J Am Chem Soc 125, 4726‐7. [33]

128. Okada, M., Sato, I., Cho, S.J., Iwata, H., Nishio, T., Dubnau, D. and Sakagami, Y. (2005). Structure of the Bacillus subtilis quorum‐sensing peptide pheromone ComX. Nat Chem Biol 1, 23‐4. [28]

129. Pavlova, O., Mukhopadhyay, J., Sineva, E., Ebright, R.H. and Severinov, K. (2008). Systematic structure‐ activity analysis of microcin J25. J Biol Chem 283, 25589‐95.

130. Notredame, C., Higgins, D.G. and Heringa, J. (2000). T‐Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol 302, 205‐17.

131. Letellier, L. and Santamaria, M. (2002). The biochemical and physiological characteristics of surface receptors of gram negative bacteria. Mini Rev Med Chem 2, 343‐51.

132. Miller, M.T., Bachmann, B.O., Townsend, C.A. and Rosenzweig, A.C. (2002). The catalytic cycle of beta ‐ lactam synthetase observed by x‐ray crystallographic snapshots. Proc Natl Acad Sci U S A 99, 14752‐7.

133. Verdine, G.L. (1996). The combinatorial chemistry of nature. Nature 384, 11‐3. [2] Newman, D.J., Cragg, G.M. and Snader, K.M. (2003). Natural products as sources of new drugs over the period 1981‐2002. J Nat Prod 66, 1022‐37. [3]

134. Blond, A. et al. (1999). The cyclic structure of microcin J25, a 21‐residue peptide antibiotic from Escherichia coli. Eur J Biochem 259, 747‐55.

135. Bode, H.B. and Muller, R. (2005). The impact of bacterial genomics on natural product research. Angew Chem Int Ed Engl 44, 6828‐46. [7]

136. Takada, Y., Ye, X. and Simon, S. (2007). The integrins. Genome Biol 8, 215.

137. Adler, N.R., Govan, B., Cullinane, M., Harper, M., Adler, B. and Boyce, J.D. (2009). The molecular and cellular basis of pathogenesis in melioidosis: how does Burkholderia pseudomallei cause disease? FEMS Microbiol Rev 33, 1079‐99.

138. Frey, P.A., Hegeman, A.D. and Ruzicka, F.J. (2008). The Radical SAM Superfamily. Crit Rev Biochem Mol Biol 43, 63‐88. [57]

139. Colgrave, M.L. and Craik, D.J. (2004). Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot. Biochemistry 43, 5965‐75. [84] Gunasekera, S., Foley, F.M., Clark, R.J., Sando, L., Fabri, L.J., Craik, D.J. and Daly, N.L. (2008). Engineering stabilized vascular endothelial growth factor‐A antagonists: synthesis, structural characterization, and bioactivity of grafted analogues of cyclotides. J Med Chem 51, 7697‐704. [85]

140. Blond, A., Cheminant, M., Destoumieux‐Garzon, D., Segalas‐Milazzo, I., Peduzzi, J., Goulard, C. and Rebuffat, S. (2002). Thermolysin‐linearized microcin J25 retains the structured core of the native macrocyclic peptide and displays antimicrobial activity. Eur J Biochem 269, 6212‐22.

141. Selsted, M.E. (2004). Theta‐defensins: cyclic antimicrobial peptides produced by binary ligation of truncated alpha‐defensins. Curr Protein Pept Sci 5, 365‐71. [36]

142. Yasin, B. et al. (2004). Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J Virol 78, 5147‐56. [93]

143. LaVallie, E.R., DiBlasio‐Smith, E.A., Collins‐Racie, L.A., Lu, Z. and McCoy, J.M. (2003). Thioredoxin and related proteins as multifunctional fusion tags for soluble expression in E. coli. Methods Mol Biol 205, 119‐40.

144. Vetter, J. (1998). Toxins of Amanita phalloides. Toxicon 36, 13‐24. [70]

145. Wirawan, R.E., Swanson, K.M., Kleffmann, T., Jack, R.W. and Tagg, J.R. (2007). Uberolysin: a novel cyclic bacteriocin produced by Streptococcus uberis. Microbiology 153, 1619‐30. [52]

146. Hwang, T.‐L. and Shaka, A.J. (1995). Water Suppression That Works. Excitation Sculpting Using Arbitary Waveforms and Pulsed Field Gradients. J. Magn. Reson. A 112, 275‐279.

147. Heng, N.C.K. and Tagg, J.R. (2006). What's in a name? Class distinction for bacteriocins. Nat Rev Micro 4 [44] Leer, R.J., van der Vossen, J.M., van Giezen, M., van Noort, J.M. and Pouwels, P.H. (1995). Genetic analysis of acidocin B, a novel bacteriocin produced by Lactobacillus acidophilus. Microbiology 141, 1629‐35. [45]

148. Marahiel, M.A. (2009). Working outside the protein‐synthesis rules: insights into non‐ribosomal peptide synthesis. J Pept Sci 15, 799‐807. [22]

149. Frau Dr. Xiulan Xie gebührt ein sehr großer Dank für das Lösen der NMR‐Strukturen von Capistruin und BI‐32169 sowie ihre ständige Hilfsbereitschaft und Kooperation beim Anfertigen der Manuskripte. Danksagung 139

150. Clarke, D.J. and Campopiano, D.J. (2007). Maturation of McjA precursor peptide into active microcin MccJ25. Org Biomol Chem 5, 2564‐6.

151. Mahenthiralingam, E., Urban, T.A. and Goldberg, J.B. (2005). The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3, 144‐56.

152. Wilson, K.A. et al. (2003). Structure of microcin J25, a peptide inhibitor of bacterial RNA polymerase, is a lassoed tail. J Am Chem Soc 125, 12475‐83.

153. Cheung, W.L., Pan, S.J. and Link, A.J. (2010). Much of the Microcin J25 Leader Peptide is Dispensable. J Am Chem Soc 132, 2514‐5.

154. Cardona, S.T. and Valvano, M.A. (2005). An expression vector containing a rhamnose‐inducible promoter provides tightly regulated gene expression in Burkholderia cenocepacia. Plasmid 54, 219‐28.

155. Semenova, E., Yuzenkova, Y., Peduzzi, J., Rebuffat, S. and Severinov, K. (2005). Structure‐activity analysis of microcinJ25: distinct parts of the threaded lasso molecule are responsible for interaction with bacterial RNA polymerase. J Bacteriol 187, 3859‐63.

156. Cole, A.M. et al. (2002). Retrocyclin: a primate peptide that protects cells from infection by T‐ and M‐ tropic strains of HIV‐1. Proc Natl Acad Sci U S A 99, 1813‐8. [92]

157. Griffin, M., Casadio, R. and Bergamini, C.M. (2002). Transglutaminases: nature's biological glues. Biochem J 368, 377‐96.

158. Chokekijchai, S. et al. (1995). NP‐06: a novel anti‐human immunodeficiency virus polypeptide produced by a Streptomyces species. Antimicrob Agents Chemother 39, 2345‐7.

159. Lin, P.F. et al. (1996). Characterization of siamycin I, a human immunodeficiency virus fusion inhibitor. Antimicrob Agents Chemother 40, 133‐8.

160. Poirot, O., O'Toole, E. and Notredame, C. (2003). Tcoffee@igs: A web server for computing, evaluating and combining multiple sequence alignments. Nucleic Acids Res 31, 3503‐6.

161. Salomon, R.A. and Farias, R.N. (1995). The peptide antibiotic microcin 25 is imported through the TonB pathway and the SbmA protein. J Bacteriol 177, 3323‐5.

162. Solbiati, J.O., Ciaccio, M., Farias, R.N. and Salomon, R.A. (1996). Genetic analysis of plasmid determinants for microcin J25 production and immunity. J Bacteriol 178, 3661‐3.

163. Udwary, D.W., Zeigler, L., Asolkar, R.N., Singan, V., Lapidus, A., Fenical, W., Jensen, P.R. and Moore, B.S. (2007). Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc Natl Acad Sci U S A 104, 10376‐81. [14]

164. Salomon, R.A. and Farias, R.N. (1993). The FhuA protein is involved in microcin 25 uptake. J Bacteriol 175, 7741‐2.

165. Salomon, R.A. and Farias, R.N. (1992). Microcin 25, a novel antimicrobial peptide produced by Escherichia coli. J Bacteriol 174, 7428‐35.

166. Hallen, H.E., Luo, H., Scott‐Craig, J.S. and Walton, J.D. (2007). Gene family encoding the major toxins of lethal Amanita mushrooms. Proc Natl Acad Sci U S A 104, 19097‐101. [73]

167. Makarova, K.S., Aravind, L. and Koonin, E.V. (1999). A superfamily of archaeal, bacterial, and eukaryotic proteins homologous to animal transglutaminases. Protein Sci 8, 1714‐9.

168. Jones, A.C., Gu, L., Sorrels, C.M., Sherman, D.H. and Gerwick, W.H. (2009). New tricks from ancient algae: natural products biosynthesis in marine cyanobacteria. Curr Opin Chem Biol 13, 216‐23. [64]

169. Chandler, J.R., Duerkop, B.A., Hinz, A., West, T.E., Herman, J.P., Churchill, M.E., Skerrett, S.J. and Greenberg, E.P. (2009). Mutational analysis of Burkholderia thailandensis quorum sensing and self‐ aggregation. J Bacteriol 191, 5901‐9.

170. Mukhopadhyay, J., Sineva, E., Knight, J., Levy, R.M. and Ebright, R.H. (2004). Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol Cell 14, 739‐51.

171. Seyedsayamdost, M.R., Chandler, J.R., Blodgett, J.A., Lima, P.S., Duerkop, B.A., Oinuma, K., Greenberg, E.P. and Clardy, J. (2010). Quorum‐sensing‐regulated bactobolin production by Burkholderia thailandensis E264. Org Lett 12, 716‐9.

172. Donia, M.S., Ravel, J. and Schmidt, E.W. (2008). A global assembly line for cyanobactins. Nat Chem Biol 4, 341‐3. [63]

173. Delgado, M.A., Solbiati, J.O., Chiuchiolo, M.J., Farias, R.N. and Salomon, R.A. (1999). Escherichia coli outer membrane protein TolC is involved in production of the peptide antibiotic microcin J25. J Bacteriol 181, 1968‐70.

174. Solbiati, J.O., Ciaccio, M., Farias, R.N., Gonzalez‐Pastor, J.E., Moreno, F. and Salomon, R.A. (1999). Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25. J Bacteriol 181, 2659‐62.

175. Chiuchiolo, M.J., Delgado, M.A., Farias, R.N. and Salomon, R.A. (2001). Growth‐phase‐dependent expression of the cyclopeptide antibiotic microcin J25. J Bacteriol 183, 1755‐64.

176. Delgado, M.A., Rintoul, M.R., Farias, R.N. and Salomon, R.A. (2001). Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25. J Bacteriol 183, 4543‐50.

177. Knappe, T.A., Linne, U., Robbel, L. and Marahiel, M.A. (2009). Insights into the biosynthesis and stability of the lasso peptide capistruin. Chem Biol 16, 1290‐8.

178. Sutyak, K.E., Anderson, R.A., Dover, S.E., Feathergill, K.A., Aroutcheva, A.A., Faro, S. and Chikindas, M.L. (2008). Spermicidal activity of the safe natural antimicrobial peptide subtilosin. Infect Dis Obstet Gynecol 2008, 540758. [62]

179. Knappe, T.A., Eckert, B., Schaarschmidt, P., Scholz, C. and Schmid, F.X. (2007). Insertion of a chaperone domain converts FKBP12 into a powerful catalyst of protein folding. J Mol Biol 368, 1458‐68.

180. Scholz, C., Schaarschmidt, P., Engel, A.M., Andres, H., Schmitt, U., Faatz, E., Balbach, J. and Schmid, F.X. (2005). Functional solubilization of aggregation‐prone HIV envelope proteins by covalent fusion with chaperone modules. J Mol Biol 345, 1229‐41.

181. Scholz, C. et al. (2008). Chaperone‐aided in vitro renaturation of an engineered E1 envelope protein for detection of anti‐Rubella virus IgG antibodies. Biochemistry 47, 4276‐87.

182. Weininger, U. et al. (2009). NMR solution structure of SlyD from Escherichia coli: spatial separation of prolyl isomerase and chaperone function. J Mol Biol 387, 295‐305.

183. Guijarro, J.I., Gonzalez‐Pastor, J.E., Baleux, F., San Millan, J.L., Castilla, M.A., Rico, M., Moreno, F. and Delepierre, M. (1995). Chemical structure and translation inhibition studies of the antibiotic microcin C7. J Biol Chem 270, 23520‐32. [38]

184. Rebuffat, S., Blond, A., Destoumieux‐Garzon, D., Goulard, C. and Peduzzi, J. (2004). Microcin J25, from the macrocyclic to the lasso structure: implications for biosynthetic, evolutionary and biotechnological perspectives. Curr Protein Pept Sci 5, 383‐91. [37]

185. Thomas, X. et al. (2004). Siderophore peptide, a new type of post‐translationally modified antibacterial peptide with potent activity. J Biol Chem 279, 28233‐42. [41]

186. Destoumieux‐Garzon, D., Duquesne, S., Peduzzi, J., Goulard, C., Desmadril, M., Letellier, L., Rebuffat, S. and Boulanger, P. (2005). The iron‐siderophore transporter FhuA is the receptor for the antimicrobial peptide microcin J25: role of the microcin Val11‐Pro16 beta‐hairpin region in the recognition mechanism. Biochem J 389, 869‐76.

187. Duquesne, S., Destoumieux‐Garzon, D., Zirah, S., Goulard, C., Peduzzi, J. and Rebuffat, S. (2007). Two enzymes catalyze the maturation of a lasso peptide in Escherichia coli. Chem Biol 14, 793‐803.

188. Knappe, T.A., Linne, U., Zirah, S., Rebuffat, S., Xie, X. and Marahiel, M.A. (2008). Isolation and structural characterization of capistruin, a lasso peptide predicted from the genome sequence of Burkholderia thailandensis E264. J Am Chem Soc 130, 11446‐54.

189. De Clercq, E. (2000). Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med Res Rev 20, 323‐49.