Mechanistic aspects of lanthipeptide leaders

Current Protein and Peptide Science

Volumn 14, Issue 2, 2013, Pages 85-96

  Plat, Annechien ^a   Kuipers, Anneke ^b   Rink, Rick ^b   Moll, Gert N ^b  

^a UNIVERSITY OF GRONINGEN   (Netherlands)

^b Lanthio Pharma   (Netherlands)

Author keywords

Cyclase; Dehydratase; Lanthionine; Lanthipeptide; Lantibiotic; Leader; Nisin

Indexed keywords

BACTERIAL PROTEIN; LANTHIPEPTIDE; LANTHIPEPTIDE CLASS 1; LANTHIPEPTIDE CLASS 2; LANTHIPEPTIDE CLASS 3; LANTHIPEPTIDE CLASS 4; LANTIBIOTIC; NISIN; PEPTIDASE; SIGNAL PEPTIDE; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; BACTERIAL MEMBRANE; BACTERIAL STRAIN; BINDING SITE; BIOAVAILABILITY; CYCLIZATION; DEHYDRATION; ENZYME MODIFICATION; GENE CLUSTER; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN SYNTHESIS; REVIEW;

AMINO ACID SEQUENCE; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; BACTERIOCINS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR SEQUENCE DATA; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN SORTING SIGNALS;

EID: 84878574659     PISSN: 13892037     EISSN: 18755550     Source Type: Journal    
DOI: 10.2174/1389203711314020001     Document Type: Review

References (101)

1. Velasquez, J.E.; van der Donk, W.A. Genome mining for ribosomally synthesized natural products. Curr. Opin. Chem. Biol., 2011, 15, 11-21.
2. Rink, R.; Arkema-Meter, A.; Baudoin, I.; Post, E.; Kuipers, A.; Nelemans, S.A.; Akanbi, M.H.; Moll, G.N. To protect peptide pharmaceuticals against peptidases. J. Pharmacol. Toxicol. Methods, 2010, 61, 210-218.
3. Schmidt, E.W. The hidden diversity of ribosomal peptide natural products. BMC Biol., 2010, 8, 83.
4. van Heel, A.J.; Montalban-Lopez, M.; Kuipers, O.P. Evaluating the feasibility of lantibiotics as an alternative therapy against bacterial infections in humans. Expert Opin. Drug Metab. Toxicol., 2011, 7, 675-680.
5. McIntosh, J.A.; Donia, M.S.; Schmidt, E.W. Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat. Prod. Rep., 2009, 26, 537-559.
6. Arnison, P.G.; Bibb, M.J.; Bierbaum, G.; Bowers, A.A.; Bulaj, G.; Camarero, J.A.; Campopiano, D.J.; Clardy, J.; Cotter, P.D.; Craik, D.J.; Dittmann, E.; Donadio, S.; Dorrestein, P.C.; Entian, K.-D.; Fischbach, M.A.; Garavelli, J.S.; Göransson, U.; Gruber, C.W.; Haft, D.H.; Hemscheidt, T.K.; Hertweck, C.; Hill, C.; Horswill, A.R.; Jaspars, M.; Kelly, W.L.; Klinman, J.P.; Kuipers, O.P.; Link, A.J.; Liu, W.; Marahiel, M.A.; Mitchell, D.A.; Moll, G.N.; Moore, B.S.; Nair, S.K.; Nes, I.F.; Norris, G.E.; Olivera, B.M.; Onaka, H.; Reaney, M.J.T.; Rebuffat, S.; Ross, R.P.; Sahl, H.-G.; Schmidt, E.W.; Selsted, M.E.; Severinov, K.; Shen, B.; Sivonen, K.; Smith, L.; Stein, T.; Süssmuth, R.E.; Tagg, J.R.; Tang, G.; Vederas, J.C.; Walsh, C.T.; Walton, J.D.; Willey, J.M.; Van der Donk, W.A. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat. Prod. Rep., 2013, 30, 108-60.
7. Oman, T.J.; van der Donk, W.A. Follow the leader: the use of leader peptides to guide natural product biosynthesis. Nat. Chem. Biol., 2010, 6, 9-18.
8. Chatterjee, C.; Paul, M.; Xie, L.; van der Donk, W.A. Biosynthesis and mode of action of lantibiotics. Chem. Rev., 2005, 105, 633-684.
9. Willey, J.M.; van der Donk, W.A. Lantibiotics: peptides of diverse structure and function. Annu. Rev. Microbiol., 2007, 61, 477-501.
10. Bierbaum, G.; Sahl, H.-G. Lantibiotics: mode of action, biosynthesis and bioengineering. Curr. Pharm. Biotechnol., 2009, 10, 2-18.
11. Knerr, P.J.; van der Donk, W.A. Discovery, biosynthesis, and engineering of lantipeptides. Annu. Rev. Biochem., 2012, 81, 479-505.
12. [] Schnell, N.; Entian, K.-D.; Schneider, U.; Gotz, F.; Zahner, H.; Kellner, R.; Jung, G. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature, 1988, 333, 276-278.
13. Kodani, S.; Hudson, M.E.; Durrant, M.C.; Buttner, M.J.; Nodwell, J.R.; Willey, J.M. The SapB morphogen is a lantibiotic-like peptide derived from the product of the developmental gene ramS in Streptomyces coelicolor. Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 11448-11453.
14. Kodani, S.; Lodato, M.A.; Durrant, M.C.; Picart, F.; Willey, J.M. SapT, a lanthionine-containing peptide involved in aerial hyphae formation in the Streptomycetes. Mol. Microbiol., 2005, 58, 1368-1380.
15. Willey, J.M.; Willems, A.; Kodani, S.; Nodwell, J.R. Morphogenetic surfactants and their role in the formation of aerial hyphae in Streptomyces coelicolor. Mol. Microbiol., 2006, 59, 731-742.
16. Wang, H.; van der Donk, W.A. Biosynthesis of the class III lantipeptide catenulipeptin. ACS Chem. Biol., 2012.
17. Goto, Y.; Li, B.; Claesen, J.; Shi, Y.; Bibb, M.J.; van der Donk, W.A. Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLoS Biol., 2010, 8, e1000339.
18. Bierbaum, G.; Szekat, C.; Josten, M.; Heidrich, C.; Kempter, C.; Jung, G.; Sahl, H.-G. Engineering of a novel thioether bridge and role of modified residues in the lantibiotic Pep5. Appl. Environ. Microbiol., 1996, 62, 385-392.
19. Lubelski, J.; Overkamp, W.; Kluskens, L.D.; Moll, G.N.; Kuipers, O.P. Influence of shifting positions of Ser, Thr, and Cys residues in prenisin on the efficiency of modification reactions and on the antimicrobial activities of the modified prepeptides. Appl. Environ. Microbiol., 2008, 74, 4680-4685.
20. Suda, S.; Westerbeek, A.; O'Connor, P.M.; Ross, R.P.; Hill, C.; Cotter, P.D. Effect of bioengineering lacticin 3147 lanthionine bridges on specific activity and resistance to heat and proteases. Chem. Biol., 2010, 17, 1151-1160.
21. Koponen, O.; Tolonen, M.; Qiao, M.; Wahlstrom, G.; Helin, J.; Saris, P.E. NisB is required for the dehydration and NisC for the lanthionine formation in the post-translational modification of nisin. Microbiology, 2002, 148, 3561-3568.
22. Xie, L.; Miller, L.M.; Chatterjee, C.; Averin, O.; Kelleher, N.L.; van der Donk, W.A. Lacticin 481: in vitro reconstitution of lantibiotic synthetase activity. Science, 2004, 303, 679-681.
23. Müller, W.M.; Schmiederer, T.; Ensle, P.; Süssmuth, R.D. In vitro biosynthesis of the prepeptide of type-III lantibiotic labyrinthopeptin A2 including formation of a C-C bond as a posttranslational modification. Angew. Chem. Int. Ed Engl., 2010, 49, 2436-2440.
24. Meindl, K.; Schmiederer, T.; Schneider, K.; Reicke, A.; Butz, D.; Keller, S.; Guhring, H.; Vertesy, L.; Wink, J.; Hoffmann, H.; Bronstrup, M.; Sheldrick, G.M.; Süssmuth, R.D. Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew. Chem. Int. Ed Engl., 2010, 49, 1151-1154.
25. Voller, G.H.; Krawczyk, J.M.; Pesic, A.; Krawczyk, B.; Nachtigall, J.; Süssmuth, R.D. Characterization of new class III lantibiotics: erythreapeptin, avermipeptin and griseopeptin from Saccharopolyspora erythraea, Streptomyces avermitilis and Streptomyces griseus demonstrates stepwise N-terminal leader processing. Chembiochem, 2012, 13, 1174-1183.
26. Kuipers, O.P.; Rollema, H.S.; de Vos, W.M.; Siezen, R.J. 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 Lett., 1993, 330, 23-27.
27. van der Meer, J.R.; Rollema, H.S.; Siezen, R.J.; Beerthuyzen, M.M.; Kuipers, O.P.; de Vos, W.M. 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.
28. Chakicherla, A.; Hansen, J.N. Role of the leader and structural regions of prelantibiotic peptides as assessed by expressing nisinsubtilin chimeras in Bacillus subtilis 168, and characterization of their physical, chemical, and antimicrobial properties. J. Biol. Chem., 1995, 270, 23533-23539.
29. Stein, T.; Entian, K.-D. Maturation of the lantibiotic subtilin: ma-trix-assisted laser desorption/ionization time-of-flight mass spectrometry to monitor precursors and their proteolytic processing in crude bacterial cultures. Rapid Commun. Mass Spectrom., 2002, 16, 103-110.
30. Kluskens, L.D.; Kuipers, A.; Rink, R.; de Boef, E.; Fekken, S.; Driessen, A.J.; Kuipers, O.P.; Moll, G.N. Post-translational modification of therapeutic peptides by NisB, the dehydratase of the lantibiotic nisin. Biochemistry, 2005, 44, 12827-12834.
31. Li, B.; Yu, J.P.; Brunzelle, J.S.; Moll, G.N.; van der Donk, W.A.; Nair, S.K. Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis. Science, 2006, 311, 1464-1467.
32. Rink, R.; Wierenga, J.; Kuipers, A.; Kluskens, L.D.; Driessen, A.J.; Kuipers, O.P.; Moll, G.N. Production of dehydroamino acidcontaining peptides by Lactococcus lactis. Appl. Environ. Microbiol., 2007, 73, 1792-1796.
33. Patton, G.C.; Paul, M.; Cooper, L.E.; Chatterjee, C.; van der Donk, W.A. The importance of the leader sequence for directing lanthionine formation in lacticin 481. Biochemistry (N. Y.), 2008, 47, 7342-7351.
34. Nagao, J.; Morinaga, Y.; Islam, M.R.; Asaduzzaman, S.M.; Aso, Y.; Nakayama, J.; Sonomoto, K. Mapping and identification of the region and secondary structure required for the maturation of the nukacin ISK-1 prepeptide. Peptides, 2009, 30, 1412-1420.
35. Müller, W.M.; Ensle, P.; Krawczyk, B.; Süssmuth, R.D. Leader peptide-directed processing of labyrinthopeptin A2 precursor peptide by the modifying enzyme LabKC. Biochemistry, 2011, 50, 8362-8373.
36. Mavaro, A.; Abts, A.; Bakkes, P.J.; Moll, G.N.; Driessen, A.J.; Smits, S.H.; Schmitt, L. Substrate recognition and specificity of the NisB protein, the lantibiotic dehydratase involved in nisin biosynthesis. J. Biol. Chem., 2011, 286, 30552-30560.
37. Plat, A.; Kluskens, L.D.; Kuipers, A.; Rink, R.; Moll, G.N. Requirements of the engineered leader peptide of nisin for inducing modification, export, and cleavage. Appl. Environ. Microbiol., 2011, 77, 604-611.
38. Oman, T.J.; Knerr, P.J.; Bindman, N.A.; Velasquez, J.E.; van der Donk, W.A. An engineered lantibiotic synthetase that does not require a leader peptide on its substrate. J. Am. Chem. Soc., 2012, 134, 6952-6955.
39. Levengood, M.R.; Patton, G.C.; van der Donk, W.A. The leader peptide is not required for post-translational modification by lacticin 481 synthetase. J. Am. Chem. Soc., 2007, 129, 10314-10315.
40. Chen, P.; Qi, F.; Novak, J.; Krull, R.E.; Caufield, P.W. Effect of amino acid substitutions in conserved residues in the leader peptide on biosynthesis of the lantibiotic mutacin II. FEMS Microbiol. Lett., 2001, 195, 139-144.
41. Furgerson Ihnken, L.A.; Chatterjee, C.; van der Donk, W.A. In vitro reconstitution and substrate specificity of a lantibiotic protease. iochemistry, 2008, 47, 7352-7363.
42. Geissler, S.; Gotz, F.; Kupke, T. Serine protease EpiP from Staphy-lococcus epidermidis catalyzes the processing of the epidermin precursor peptide. J. Bacteriol., 1996, 178, 284-288.
43. Siezen, R.J.; Rollema, H.S.; Kuipers, O.P.; de Vos, W.M. Homol-ogy modelling of the Lactococcus lactis leader peptidase NisP and its interaction with the precursor of the lantibiotic nisin. Protein Eng., 1995, 8, 117-125.
44. Havarstein, L.S.; Diep, D.B.; Nes, I.F. A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol. Microbiol., 1995, 16, 229-240.
45. Uguen, P.; Hindre, T.; Didelot, S.; Marty, C.; Haras, D.; Le Pennec, J.P.; Vallee-Rehel, K.; Dufour, A. Maturation by LctT is required for biosynthesis of full-length lantibiotic lacticin 481. Appl. Environ. Microbiol., 2005, 71, 562-565.
46. Izaguirre, G.; Hansen, J.N. Use of alkaline phosphatase as a reporter polypeptide to study the role of the subtilin leader segment and the SpaT transporter in the posttranslational modifications and secretion of subtilin in Bacillus subtilis 168. Appl. Environ. Microbiol., 1997, 63, 3965-3971.
47. Kuipers, A.; de Boef, E.; Rink, R.; Fekken, S.; Kluskens, L.D.; Driessen, A.J.; Leenhouts, K.; Kuipers, O.P.; Moll, G.N. NisT, the transporter of the lantibiotic nisin, can transport fully modified, dehydrated, and unmodified prenisin and fusions of the leader peptide with non-lantibiotic peptides. J. Biol. Chem., 2004, 279, 22176-22182.
48. Neis, S.; Bierbaum, G.; Josten, M.; Pag, U.; Kempter, C.; Jung, G.; Sahl, H.-G. Effect of leader peptide mutations on biosynthesis of the lantibiotic Pep5. FEMS Microbiol. Lett., 1997, 149, 249-255.
49. Lian, L.Y.; Chan, W.C.; Morley, S.D.; Roberts, G.C.; Bycroft, B.W.; Jackson, D. Solution structures of nisin a and its two major degradation products determined by N.M.R. Biochem. J., 1992, 283 (Pt 2), 413-420.
50. Beck-Sickinger, A.G.; Jung, G. Synthesis and conformational analysis by CD spectroscopy of lantibiotic leader, proand prepeptides. Liebigs Ann. Chem., 1993, 1993, 1125-1131.
51. Khusainov, R.; Heils, R.; Lubelski, J.; Moll, G.N.; Kuipers, O.P. Determining sites of interaction between prenisin and its modification enzymes NisB and NisC. Mol. Microbiol., 2011, 82, 706-718.
52. Lee, M.V.; Furgerson Ihnken, L.A.; You, Y.O.; McClerren, A.L.; van der Donk, W.A.; Kelleher, N.L. Distributive and directional behavior of lantibiotic synthetases revealed by high-resolution tandem mass spectrometry. J. Am. Chem. Soc., 2009, 131, 12258-12264.
53. Okesli, A.; Cooper, L.E.; Fogle, E.J.; van der Donk, W.A. Nine post-translational modifications during the biosynthesis of cinnamycin. J. Am. Chem. Soc., 2011, 133, 13753-13760.
54. Cooper, L.E.; McClerren, A.L.; Chary, A.; van der Donk, W.A. Structure-activity relationship studies of the two-component lantibiotic haloduracin. Chem. Biol., 2008, 15, 1035-1045.
55. Nishie, M.; Shioya, K.; Nagao, J.; Jikuya, H.; Sonomoto, K. ATPdependent leader peptide cleavage by NukT, a bifunctional ABC transporter, during lantibiotic biosynthesis. J. Biosci. Bioeng., 2009, 108, 460-464.
56. Nishie, M.; Sasaki, M.; Nagao, J.; Zendo, T.; Nakayama, J.; Sonomoto, K. Lantibiotic transporter requires cooperative functioning of the peptidase domain and the ATP binding domain. J. Biol. Chem., 2011, 286, 11163-11169.
57. Caetano, T.; Krawczyk, J.M.; Mosker, E.; Süssmuth, R.D.; Mendo S. Heterologous expression, biosynthesis, and mutagenesis of type II lantibiotics from Bacillus licheniformis in Escherichia coli. Chem. Biol., 2011, 18, 90-100.
58. Goto, Y.; Okesli, A.; van der Donk, W.A. Mechanistic studies of Ser/Thr dehydration catalyzed by a member of the LanL lanthionine synthetase family. Biochemistry, 2011, 50, 891-898.
59. Lubelski, J.; Rink, R.; Khusainov, R.; Moll, G.N.; Kuipers, O.P. Biosynthesis, immunity, regulation, mode of action and engineering of the model lantibiotic nisin. Cell Mol. Life Sci., 2008, 65, 455-476.
60. Rogers, L.A. The inhibiting effect of Streptococcus lactis on Lactobacillus bulgaricus. J. Bacteriol., 1928, 16, 321-325.
61. Gross, E.; Morell, J.L. The structure of nisin. J. Am. Chem. Soc., 1971, 93, 4634-4635.
62. Velasquez, J.E.; Zhang, X.; van der Donk, W.A. Biosynthesis of the antimicrobial peptide epilancin 15X and its N-terminal lactate. Chem. Biol., 2011, 18, 857-867.
63. Kuipers, A.; Wierenga, J.; Rink, R.; Kluskens, L.D.; Driessen, A.J.; Kuipers, O.P.; Moll, G.N. Sec-mediated transport of posttranslationally dehydrated peptides in Lactococcus lactis. Appl. Environ. Microbiol., 2006, 72, 7626-7633.
64. Khusainov, R.; Kuipers, O.P. When the leader gets loose: in vivo biosynthesis of a leaderless prenisin is stimulated by a trans-acting leader peptide. Chembiochem, 2012, 13, 2433-2438.
65. Goujon, M.; McWilliam, H.; Li, W.; Valentin, F.; Squizzato, S.; Paern, J.; Lopez, R. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res., 2010, 38, W695-9.
66. Sievers, F.; Wilm, A.; Dineen, D.; Gibson, T.J.; Karplus, K.; Li, W.; Lopez, R.; McWilliam, H.; Remmert, M.; Soding, J.; Thompson, J.D.; Higgins, D.G. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol., 2011, 7, 539.
67. Meyer, C.; Bierbaum, G.; Heidrich, C.; Reis, M.; Suling, J.; Iglesias-Wind, M.I.; Kempter, C.; Molitor, E.; Sahl, H.-G. 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.
68. Kuipers, A.; Meijer-Wierenga, J.; Rink, R.; Kluskens, L.D.; Moll, G.N. Mechanistic dissection of the enzyme complexes involved in biosynthesis of lacticin 3147 and nisin. Appl. Environ. Microbiol., 2008, 74, 6591-6597.
69. Lubelski, J.; Khusainov, R.; Kuipers, O.P. Directionality and coordination of dehydration and ring formation during biosynthesis of the lantibiotic nisin. J. Biol. Chem., 2009, 284, 25962-25972.
70. Kuipers, A.; Rink, R.; Moll, G.N. Genetics, biosynthesis, structure, and mode of action of lantibiotics. Prokaryot. Antimicrob. Pept., 2011, 147-169.
71. Van den Berg van Saparoea, H.B.; Bakkes, P.J.; Moll, G.N.; Driessen, A.J. Distinct contributions of the nisin biosynthesis enzymes NisB and NisC and transporter NisT to prenisin production by Lactococcus lactis. Appl. Environ. Microbiol., 2008, 74, 5541-5548.
72. Paul, L.K.; Izaguirre, G.; Hansen, J.N. Studies of the subtilin leader peptide as a translocation signal in Escherichia coli K12. FEMS Microbiol. Lett., 1999, 176, 45-50.
73. Corvey, C.; Stein, T.; Dusterhus, S.; Karas, M.; Entian, K.-D. Activation of subtilin precursors by Bacillus subtilis extracellular serine proteases subtilisin (AprE), WprA, and Vpr. Biochem. Biophys. Res. Commun., 2003, 304, 48-54.
74. Lawton, E.M.; Ross, R.P.; Hill, C.; Cotter, P.D. Two-peptide lantibiotics: a medical perspective. Mini Rev. Med. Chem., 2007, 7, 1236-1247.
75. Zimmermann, N.; Freund, S.; Fredenhagen, A.; Jung, G. Solution structures of the lantibiotics duramycin B and C. Euro. J. Biochem., 1993, 216, 419-428.
76. Li, B.; Sher, D.; Kelly, L.; Shi, Y.; Huang, K.; Knerr, P.J.; Joewono, I.; Rusch, D.; Chisholm, S.W.; van der Donk, W.A. Catalytic promiscuity in the biosynthesis of cyclic peptide secondary metabolites in planktonic marine cyanobacteria. Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 10430-10435.
77. Tang, W.; van der Donk, W.A. Structural characterization of four prochlorosins: a novel class of lantipeptides produced by planktonic marine cyanobacteria. Biochemistry, 2012, 51, 4271-4279.
78. Shioya, K.; Harada, Y.; Nagao, J.; Nakayama, J.; Sonomoto, K. Characterization of modification enzyme NukM and engineering of a novel thioether bridge in lantibiotic nukacin ISK-1. Appl. Microbiol. Biotechnol., 2010, 86, 891-899.
79. Miller, L.M.; Chatterjee, C.; van der Donk, W.A.; Kelleher, N.L. The dehydratase activity of lacticin 481 synthetase is highly processive. J. Am. Chem. Soc., 2006, 128, 1420-1421.
80. Gilmore, M.S.; Skaugen, M.; Nes, I. Enterococcus faecalis cytolysin and Lactocin S of Lactobacillus sake. Antonie Van Leeuwenhoek, 1996, 69, 129-138.
81. Booth, M.C.; Bogie, C.P.; Sahl, H.-G.; Siezen, R.J.; Hatter, K.L.; Gilmore, M.S. Structural analysis and proteolytic activation of Enterococcus faecalis cytolysin, a novel lantibiotic. Mol. Microbiol., 1996, 21, 1175-1184.
82. Holo, H.; Jeknic, Z.; Daeschel, M.; Stevanovic, S.; Nes, I.F. Plantaricin W from Lactobacillus plantarum belongs to a new family of two-peptide lantibiotics. Microbiology, 2001, 147, 643-651.
83. McClerren, A.L.; Cooper, L.E.; Quan, C.; Thomas, P.M.; Kelleher, N.L.; van der Donk, W.A. Discovery and in vitro biosynthesis of haloduracin, a two-component lantibiotic. Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 17243-17248.
84. Krawczyk, B.; Völler, G.H.; Völler, J.; Ensle, P.; Süssmuth, R.D. Curvopeptin: a new lanthionine-containing class III lantibiotic and its co-substrate promiscuous synthetase. Chem. BioChem., 2012.
85. Krawczyk, B.; Ensle, P.; Müller, W.M.; Süssmuth, R.D. Deuterium labeled peptides give insights into the directionality of class III lantibiotic synthetase LabKC. J. Am. Chem. Soc., 2012, 134, 9922-9925.
86. Jung, G. Enzyme-catalyzed sulfide ring formation in lantibiotics. Angew. Chem. Int. Ed Engl., 2006, 45, 5919-5921.
87. Kupke, T.; Kempter, C.; Gnau, V.; Jung, G.; Gotz, F. 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.
88. Majchrzykiewicz, J.A.; Lubelski, J.; Moll, G.N.; Kuipers, A.; Bijlsma, J.J.; Kuipers, O.P.; Rink, R. Production of a class II twocomponent lantibiotic of Streptococcus pneumoniae using the class I nisin synthetic machinery and leader sequence. Antimicrob. Agents Chemother., 2010, 54, 1498-1505.
89. Levengood, M.R.; Kerwood, C.C.; Chatterjee, C.; van der Donk, W.A. Investigation of the substrate specificity of lacticin 481 synthetase by using nonproteinogenic amino acids. Chem. Biochem., 2009, 10, 911-919.
90. Rink, R.; Kuipers, A.; de Boef, E.; Leenhouts, K.J.; Driessen, A.J.; Moll, G.N.; Kuipers, O.P. Lantibiotic structures as guidelines for the design of peptides that can be modified by lantibiotic enzymes. Biochemistry, 2005, 44, 8873-8882.
91. Levengood, M.R.; van der Donk, W.A. Use of lantibiotic synthetases for the preparation of bioactive constrained peptides. Bioorg. Med. Chem. Lett., 2008, 18, 3025-3028.
92. Kluskens, L.D.; Nelemans, S.A.; Rink, R.; de Vries, L.; MeterArkema, A.; Wang, Y.; Walther, T.; Kuipers, A.; Moll, G.N.; Haas, M. Angiotensin-(1-7) with thioether bridge: an angiotensinconverting enzyme-resistant, potent angiotensin-(1-7) analog. J. Pharmacol. Exp. Ther., 2009, 328, 849-854.
93. de Vries, L.; Reitzema-Klein, C.E.; Meter-Arkema, A.; van Dam, A.; Rink, R.; Moll, G.N.; Akanbi, M.H. Oral and pulmonary delivery of thioether-bridged angiotensin-(1-7). Peptides, 2010, 31, 893-898.
94. Wösten-van Asperen, R.M.; Lutter, R.; Specht, P.A.; Moll, G.N.; van Woensel, J.B.; van der Loos, C.M.; van Goor, H.; Kamilic, J.; Florquin, S.; Bos, A.P. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J. Pathol., 2011, 225, 618-627.
95. Durik, M.; Van Veghel, R.; Kuipers, A.; Rink, R.; Haas Jimoh Akanbi, M.; Moll, G.N.; Danser, A.H.J.; Roks, A.J.M. The effect of the thioether-bridged, stabilized angiotensin-(1-7) analogue cy-clic Ang-(1-7) on cardiac remodeling and endothelial function in rats with myocardial infarction. Internat. J. Hypertension, 2012, 2012.
96. Kuipers, A.; Rink, R.; Moll, G.N. Translocation of a thioetherbridged azurin peptide fragment via the Sec pathway in Lactococcus lactis. Appl. Environ. Microbiol., 2009, 75, 3800-3802.
97. Levengood, M.R.; Knerr, P.J.; Oman, T.J.; van der Donk, W.A. In vitro mutasynthesis of lantibiotic analogues containing nonproteinogenic amino acids. J. Am. Chem. Soc., 2009, 131, 12024-12025.
98. Shi, Y.; Yang, X.; Garg, N.; van der Donk, W.A. Production of lantipeptides in Escherichia coli. J. Am. Chem. Soc., 2011, 133, 2338-2341.
99. [99] Oldach, F.; Al Toma, R.; Kuthning, A.; Caetano, T.; Mendo, S.; Budisa, N.; Süssmuth, R.D. Congeneric lantibiotics from ribosomal in vivo peptide synthesis with noncanonical amino acids. Angew. Chem. Int. Ed Engl., 2012, 51, 415-418.
100. Bosma, T.; Kuipers, A.; Bulten, E.; de Vries, L.; Rink, R.; Moll, G.N. Bacterial display and screening of posttranslationally thioether-stabilized peptides. Appl. Environ. Microbiol., 2011, 77, 6794-6801.
101. Chatterjee, C.; Patton, G.C.; Cooper, L.; Paul, M.; van der Donk, W.A. Engineering dehydro amino acids and thioethers into peptides using lacticin 481 synthetase. Chem. Biol., 2006, 13, 1109-1117.