Bioengineering lantibiotics for therapeutic success

Frontiers in Microbiology

Volumn 6, Issue NOV, 2015, Pages

  Field, Des ^a   Cotter, Paul D ^b,c   Hill, Colin ^a,c   Ross, R P ^b,c  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b TEAGASC FOOD RESEARCH CENTRE   (Ireland)

^c UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Antimicrobial peptide; Bacterial resistance; Bacteriocin; Lantibiotic; Mutagenesis; Nisin; Post translational modification

Indexed keywords

CEFOTAXIME; CEFTRIAXONE; CHYMOTRYPSIN; CLARITHROMYCIN; COLISTIN; DEOXYACTAGARDINE B; EPIDERMIN; LACTICIN 3147; LACTICIN 481; LANTIBIOTIC; MERSACIDIN; MICROBSPORICIN; MUTACIN 1140; MUTACIN B NY266; NISIN; NUKACIN ISK 1; NVB 302; PEP5; PLANOSPORICIN; PSEUDOMYCOICIDIN; RAMOPLANIN; TRYPSIN; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; BIOENGINEERING; CLOSTRIDIUM DIFFICILE INFECTION; COST EFFECTIVENESS ANALYSIS; DRUG DIFFUSION; DRUG POTENTIATION; DRUG SOLUBILITY; ESCHERICHIA COLI INFECTION; GRAM POSITIVE INFECTION; HELICOBACTER INFECTION; HUMAN; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION; NEISSERIACEAE INFECTION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PROPIONIBACTERIUM ACNES; PROTEIN DEGRADATION; PROTEIN ENGINEERING; PROTEIN EXPRESSION; SHORT SURVEY; STAPHYLOCOCCUS INFECTION; STRUCTURE ACTIVITY RELATION; SYNTHETIC BIOLOGY; THERMOSTABILITY; VANCOMYCIN RESISTANT ENTEROCOCCUS;

EID: 84949809882     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.01363     Document Type: Short Survey

References (86)

1. Appleyard, A. N., Choi, S., Read, D. M., Lightfoot, A., Boakes, S., Hoffmann, A., et al. (2009). Dissecting structural and functional diversity of the lantibiotic mersacidin. Chem. Biol. 16, 490-498. doi: 10.1016/j.chembiol.2009.03.011
2. Arnusch, C. J., Bonvin, A. M., Verel, A. M., Jansen, W. T., Liskamp, R. M., de Kruijff, B., et al. (2008). The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant Enterococci. Biochemistry 47, 12661-12663. doi: 10.1021/bi801597b
3. Basi-Chipalu, S., Dischinger, J., Josten, M., Szekat, C., Zweynert, A., Sahl, H. G., et al. (2015). Pseudomycoicidin, a Class II Lantibiotic from Bacillus pseudomycoides. Appl. Environ. Microbiol. 81, 3419-3429. doi: 10.1128/AEM.00299-15
4. Bierbaum, G., Szekat, C., Josten, M., Heidrich, C., Kempter, C., Jung, G., et al. (1996). Engineering of a novel thioether bridge and role of modified residues in the lantibiotic Pep5. Appl. Environ. Microbiol. 62, 385-392.
5. Boakes, S., Appleyard, A. N., Cortes, J., and Dawson, M. J. (2010). Organization of the biosynthetic genes encoding deoxyactagardine B (DAB), a new lantibiotic produced by Actinoplanes liguriae NCIMB41362. J. Antibiot (Tokyo) 63, 351-358. doi: 10.1038/ja.2010.48
6. Bonelli, R. R., Schneider, T., Sahl, H. G., and Wiedemann, I. (2006). Insights into in vivo activities of lantibiotics from gallidermin and epidermin mode-of-action studies. Antimicrob. Agents Chemother. 50, 1449-1457. doi: 10.1128/AAC.50.4.1449-1457.2006
7. Breukink, E., and de Kruijff, B. (2006). Lipid II as a target for antibiotics. Nat. Rev. Drug Discov. 5, 321-332. doi: 10.1038/nrd2004
8. Brumfitt, W., Salton, M. R., and Hamilton-Miller, J. M. (2002). Nisin, alone and combined with peptidoglycan-modulating antibiotics: activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. J. Antimicrob. Chemother. 50, 731-734. doi: 10.1093/jac/dkf190
9. Burton, J. P., Chilcott, C. N., Moore, C. J., Speiser, G., and Tagg, J. R. (2006). A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J. Appl. Microbiol. 100, 754-764. doi: 10.1111/j.1365-2672.2006.02837.x
10. Caetano, T., Barbosa, J., Moesker, E., Sussmuth, R. D., and Mendo, S. (2014). Bioengineering of lanthipeptides in Escherichia coli: assessing the specificity of lichenicidin and haloduracin biosynthetic machinery. Res. Microbiol. 165, 600-604. doi: 10.1016/j.resmic.2014.07.006
11. Caetano, T., Krawczyk, J. M., Mosker, E., Sussmuth, R. D., and Mendo, S. (2011). Heterologous expression, biosynthesis, and mutagenesis of type II lantibiotics from Bacillus licheniformis in Escherichia coli. Chem. Biol. 18, 90-100. doi: 10.1016/j.chembiol.2010.11.010
12. Castiglione, F., Cavaletti, L., Losi, D., Lazzarini, A., Carrano, L., Feroggio, M., et al. (2007). A novel lantibiotic acting on bacterial cell wall synthesis produced by the uncommon actinomycete Planomonospora sp. Biochemistry 46, 5884-5895. doi: 10.1021/bi700131x
13. Castiglione, F., Lazzarini, A., Carrano, L., Corti, E., Ciciliato, I., Gastaldo, L., et al. (2008). Determining the structure and mode of action of microbisporicin, a potent lantibiotic active against multiresistant pathogens. Chem. Biol. 15, 22-31. doi: 10.1016/j.chembiol.2007.11.009
14. Cavera, V. L., Arthur, T. D., Kashtanov, D., and Chikindas, M. L. (2015). Bacteriocins and their position in the next wave of conventional antibiotics. Int. J. Antimicrob. Agents 46, 494-501. doi: 10.1016/j.ijantimicag.2015.07.011
15. Chen, S., Wilson-Stanford, S., Cromwell, W., Hillman, J. D., Guerrero, A., Allen, C. A., et al. (2013). Site-directed mutations in the lanthipeptide mutacin 1140. Appl. Environ. Microbiol. 79, 4015-4023. doi: 10.1128/AEM.00704-13
16. Cotter, P. D., Hill, C., and Ross, R. P. (2005). Bacterial lantibiotics: strategies to improve therapeutic potential. Curr. Protein Pept. Sci. 6, 61-75. doi: 10.2174/1389203053027584
17. Cotter, P. D., Ross, R. P., and Hill, C. (2013). Bacteriocins-a viable alternative to antibiotics? Nat. Rev. Microbiol. 11, 95-105. doi: 10.1038/nrmicro2937
18. Dawson, M. J., and Scott, R. W. (2012). New horizons for host defense peptides and lantibiotics. Curr. Opin. Pharmacol. 12, 545-550. doi: 10.1016/j.coph.2012.06.006
19. De Kwaadsteniet, M., Doeschate, K. T., and Dicks, L. M. (2009). Nisin F in the treatment of respiratory tract infections caused by Staphylococcus aureus. Lett. Appl. Microbiol. 48, 65-70. doi: 10.1111/j.1472-765X.2008.02488.x
20. Delves-Broughton, J. (2005). Nisin as a food preservative. Food Australia 57, 525-527.
21. Dierksen, K. P., Moore, C. J., Inglis, M., Wescombe, P. A., and Tagg, J. R. (2007). The effect of ingestion of milk supplemented with salivaricin A-producing Streptococcus salivarius on the bacteriocin-like inhibitory activity of streptococcal populations on the tongue. FEMS Microbiol. Ecol. 59, 584-591. doi: 10.1111/j.1574-6941.2006.00228.x
22. Dischinger, J., Basi Chipalu, S., and Bierbaum, G. (2014). Lantibiotics: promising candidates for future applications in health care. Int. J. Med. Microbiol. 304, 51-62. doi: 10.1016/j.ijmm.2013.09.003
23. Escano, J., and Smith, L. (2015). Multipronged approach for engineering novel peptide analogues of existing lantibiotics. Expert. Opin. Drug Discov. 10, 857-870. doi: 10.1517/17460441.2015.1049527
24. Férir, G., Petrova, M. I., Andrei, G., Huskens, D., Hoorelbeke, B., Snoeck, R., et al. (2013). The Lantibiotic peptide labyrinthopeptin A1 demonstrates broad Anti-HIV and Anti-HSV activity with potential for microbicidal applications. PLoS ONE 8:e64010. doi: 10.1371/journal.pone.0064010
25. Field, D., Begley, M., O'Connor, P. M., Daly, K. M., Hugenholtz, F., Cotter, P. D., et al. (2012). Bioengineered nisin a derivatives with enhanced activity against both gram positive and gram negative pathogens. PLoS ONE 7:e46884. doi: 10.1371/journal.pone.0046884
26. Field, D., Gaudin, N., Lyons, F., O'Connor, P. M., Cotter, P. D., Hill, C., et al. (2015). A bioengineered nisin derivative to control biofilms of Staphylococcus pseudintermedius. PLoS ONE 10:e0119684. doi: 10.1371/journal.pone.0119684
27. Field, D., Molloy, E. M., Iancu, C., Draper, L. A., PM, O. C., Cotter, P. D., et al. (2013). Saturation mutagenesis of selected residues of the alpha-peptide of the lantibiotic lacticin 3147 yields a derivative with enhanced antimicrobial activity. Microb. Biotechnol. 6, 564-575. doi: 10.1111/1751-7915.12041
28. Field, D., O'Connor, P. M., Cotter, P. D., Hill, C., and Ross, R. P. (2008). The generation of nisin variants with enhanced activity against specific gram-positive pathogens. Mol. Microbiol. 69, 218-230. doi: 10.1111/j.1365-2958.2008.06279.x
29. Fontana, M. B., de Bastos Mdo, C., and Brandelli, A. (2006). Bacteriocins Pep5 and epidermin inhibit Staphylococcus epidermidis adhesion to catheters. Curr. Microbiol. 52, 350-353. doi: 10.1007/s00284-005-0152-5
30. Galvin, M., Hill, C., and Ross, R. P. (1999). Lacticin 3147 displays activity in buffer against gram-positive bacterial pathogens which appear insensitive in standard plate assays. Lett. Appl. Microbiol. 28, 355-358. doi: 10.1046/j.1365-2672.1999.00550.x
31. Ghobrial, O. G., Derendorf, H., and Hillman, J. D. (2009). Pharmacodynamic activity of the lantibiotic MU1140. Int. J. Antimicrob. Agents 33, 70-74. doi: 10.1016/j.ijantimicag.2008.07.028
32. Giacometti, A., Cirioni, O., Barchiesi, F., and Scalise, G. (2000). In vitro activity and killing effect of polycationic peptides on methicillin-resistant Staphylococcus aureus and interactions with clinically used antibiotics. Diagn. Microbiol. Infect. Dis. 38, 115-118. doi: 10.1016/S0732-8893(00)00175-9
33. Grasemann, H., Stehling, F., Brunar, H., Widmann, R., Laliberte, T. W., Molina, L., et al. (2007). Inhalation of Moli1901 in patients with cystic fibrosis. Chest 131, 1461-1466. doi: 10.1378/chest.06-2085
34. Gut, I. M., Prouty, A. M., Ballard, J. D., van der Donk, W. A., and Blanke, S. R. (2008). Inhibition of Bacillus anthracis spore outgrowth by nisin. Antimicrob. Agents Chemother. 52, 4281-4288. doi: 10.1128/AAC.00625-08
35. Healy, B., Field, D., O'Connor, P. M., Hill, C., Cotter, P. D., and Ross, R. P. (2013). Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives. PLoS ONE 8:e79563. doi: 10.1371/journal.pone.0079563
36. Hillman, J. D. (2002). Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie Van Leeuwenhoek 82, 361-366. doi: 10.1023/A:1020695902160
37. Hoffmann, A., Pag, U., Wiedemann, I., and Sahl, H. G. (2002). Combination of antibiotic mechanisms in lantibiotics. Farmaco 57, 685-691. doi: 10.1016/S0014-827X(02)01208-9
38. Hsu, S. T., Breukink, E., Tischenko, E., Lutters, M. A., de Kruijff, B., Kaptein, R., et al. (2004). The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics. Nat. Struct. Mol. Biol. 11, 963-967. doi: 10.1038/nsmb830
39. Iorio, M., Sasso, O., Maffioli, S. I., Bertorelli, R., Monciardini, P., Sosio, M., et al. (2014). A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. ACS Chem. Biol. 9, 398-404. doi: 10.1021/cb400692w
40. Islam, M. R., Shioya, K., Nagao, J., Nishie, M., Jikuya, H., Zendo, T., et al. (2009). Evaluation of essential and variable residues of nukacin ISK-1 by NNK scanning. Mol. Microbiol. 72, 1438-1447. doi: 10.1111/j.1365-2958.2009.06733.x
41. Jabes, D., Brunati, C., Candiani, G., Riva, S., Romano', G., and Donadio, S. (2011). Efficacy of the new lantibiotic NAI-107 in experimental infections induced by MDR Gram positive pathogens. Antimicrob. Agents Chemother. 55, 1671-1676. doi: 10.1128/AAC.01288-10
42. Jarvis, B., and Mahoney, R. R. (1969). Inactivation of nisin by alpha-chymotrypsin. J. Dairy Sci. 52, 1448-1449. doi: 10.3168/jds. S0022-0302(69)86771-8
43. Joo, N. E., Ritchie, K., Kamarajan, P., Miao, D., and Kapila, Y. L. (2012). Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1. Cancer Med. 1, 295-305. doi: 10.1002/cam4.35
44. Kamarajan, P., Hayami, T., Matte, B., Liu, Y., Danciu, T., Ramamoorthy, A., et al. (2015). Nisin ZP, a bacteriocin and food preservative, inhibits head and neck cancer tumorigenesis and prolongs survival. PLoS ONE 10:e0131008. doi: 10.1371/journal.pone.0131008
45. Knerr, P. J., and van der Donk, W. A. (2012). Chemical synthesis and biological activity of analogues of the lantibiotic epilancin 15X. J. Am. Chem. Soc. 134, 7648-7651. doi: 10.1021/ja302435y
46. Kong, W., and Lu, T. (2014). Cloning and optimization of a nisin biosynthesis pathway for bacteriocin harvest. ACS Synth. Biol. 3, 439-445. doi: 10.1021/sb500225r
47. Koopmans, T., Wood, T. M., Hart, T.P., Kleijn, L. H., Hendrickx, A. P., Willems, R. J., et al. (2015). Semisynthetic lipopeptides derived from nisin display antibacterial activity and lipid II binding on par with that of the parent compound. J. Am. Chem. Soc. 137, 9382-9389. doi: 10.1021/jacs.5b04501
48. Kruszewska, D., Sahl, H. G., Bierbaum, G., Pag, U., Hynes, S. O., and Ljungh, A. (2004). Mersacidin eradicates methicillin-resistant Staphylococcus aureus (MRSA) in a mouse rhinitis model. J. Antimicrob. Chemother. 54, 648-653. doi: 10.1093/jac/dkh387
49. Kuthning, A., Mosker, E., and Sussmuth, R. D. (2015). Engineering the heterologous expression of lanthipeptides in Escherichia coli by multigene assembly. Appl. Microbiol. Biotechnol. 99, 6351-6361. doi: 10.1007/s00253-015-6557-6
50. Kuwano, K., Tanaka, N., Shimizu, T., Nagatoshi, K., Nou, S., and Sonomoto, K. (2005). Dual antibacterial mechanisms of nisin Z against Gram-positive and Gram-negative bacteria. Int. J. Antimicrob. Agents 26, 396-402. doi: 10.1016/j.ijantimicag.2005.08.010
51. Lawton, E. M., Ross, R. P., Hill, C., and Cotter, P. D. (2007). Two-peptide lantibiotics: a medical perspective. Mini Rev. Med. Chem. 7, 1236-1247. doi: 10.2174/138955707782795638
52. Levengood, M. R., Knerr, P. J., Oman, T. J., and van der Donk, W. A. (2009). In vitro mutasynthesis of lantibiotic analogues containing non-proteinogenic amino acids. J. Am. Chem. Soc. 131, 12024-12025. doi: 10.1021/ja903239s
53. Li, B., Cooper, L. E., and van der Donk, W. A. (2009). In vitro studies of lantibiotic biosynthesis. Methods Enzymol. 458, 533-558. doi: 10.1016/S0076-6879(09)04821-6
54. Marki, F., Hanni, E., Fredenhagen, A., and van Oostrum, J. (1991). Mode of action of the lanthionine-containing peptide antibiotics duramycin, duramycin B and C, and cinnamycin as indirect inhibitors of phospholipase A2. Biochem. Pharmacol. 42, 2027-2035. doi: 10.1016/0006-2952(91)90604-4
55. Meindl, K., Schmiederer, T., Schneider, K., Reicke, A., Butz, D., Keller, S., et al. (2010). Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew. Chem. Int. Ed. Engl. 49, 1151-1154. doi: 10.1002/anie.200905773
56. Mohr, K. I., Volz, C., Jansen, R., Wray, V., Hoffmann, J., Bernecker, S., et al. (2015). Pinensins: the first antifungal lantibiotics. Angew. Chem. Int. Ed. 54, 11254-11258. doi: 10.1002/anie.201500927
57. Molloy, E. M., Field, D., Connor, P. M. O., Cotter, P. D., Hill, C., and Ross, R. P. (2013). Saturation mutagenesis of lysine 12 leads to the identification of derivatives of nisin a with enhanced antimicrobial activity. PLoS ONE 8:e58530. doi: 10.1371/journal.pone.0058530
58. Mota-Meira, M., LaPointe, G., Lacroix, C., and Lavoie, M. C. (2000). MICs of mutacin B-Ny266, nisin A, vancomycin, and oxacillin against bacterial pathogens. Antimicrob. Agents Chemother. 44, 24-29. doi: 10.1128/AAC.44.1.24-29.2000
59. Mota-Meira, M., Morency, H., and Lavoie, M. C. (2005). In vivo activity of mutacin B-Ny266. J. Antimicrob. Chemother. 56, 869-871. doi: 10.1093/jac/dki295
60. Nagao, J., Aso, Y., Shioya, K., Nakayama, J., and Sonomoto, K. (2007). Lantibiotic engineering: molecular characterization and exploitation of lantibiotic-synthesizing enzymes for peptide engineering. J. Mol. Microbiol. Biotechnol. 13, 235-242. doi: 10.1159/000104749
61. Nerandzic, M. M., and Donskey, C. J. (2010). Triggering germination represents a novel strategy to enhance killing of Clostridium difficile Spores. PLoS ONE 5:e12285. doi: 10.1371/journal.pone.0012285
62. Nikaido, H., and Vaara, M. (1985). Molecular basis of bacterial outer membrane permeability. Microbiol. Rev. 49, 1-32.
63. Niu, W. W., and Neu, H. C. (1991). Activity of mersacidin, a novel peptide, compared with that of vancomycin, teicoplanin, and daptomycin. Antimicrob. Agents Chemother. 35, 998-1000. doi: 10.1128/AAC.35.5.998
64. Oliynyk, I., Varelogianni, G., Roomans, G. M., and Johannesson, M. (2010). Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia. APMIS 118, 982-990. doi: 10.1111/j.1600-0463.2010.02680.x
65. Pag, U., and Sahl, H. G. (2002). Multiple activities in lantibiotics-models for the design of novel antibiotics? Curr. Pharm Des. 8, 815-833. doi: 10.2174/1381612023395439
66. Piper, C., Cotter, P. D., Ross, R. P., and Hill, C. (2009a). Discovery of medically significant lantibiotics. Curr. Drug Discov. Technol. 6, 1-18. doi: 10.2174/157016309787581075
67. Piper, C., Draper, L. A., Cotter, P. D., Ross, R. P., and Hill, C. (2009b). A comparison of the activities of lacticin 3147 and nisin against drug-resistant Staphylococcus aureus and Enterococcus species. J. Antimicrob. Chemother. 64, 546-551. doi: 10.1093/jac/dkp221
68. Rea, M. C., Clayton, E., O'Connor, P. M., Shanahan, F., Kiely, B., Ross, R. P., et al. (2007). Antimicrobial activity of lacticin 3,147 against clinical Clostridium difficile strains. J. Med. Microbiol. 56, 940-946. doi: 10.1099/jmm.0.47085-0
69. Rink, R., Wierenga, J., Kuipers, A., Kluskens, L. D., Driessen, A. J., Kuipers, O. P., et al. (2007). Dissection and modulation of the four distinct activities of nisin by mutagenesis of rings A and B and by C-terminal truncation. Appl. Environ. Microbiol. 73, 5809-5816. doi: 10.1128/AEM.01104-07
70. Rishi, P., Preet Singh, A., Garg, N., and Rishi, M. (2014). Evaluation of nisin-beta-lactam antibiotics against clinical strains of Salmonella enterica serovar Typhi. J Antibiot (Tokyo) 67, 807-811. doi: 10.1038/ja.2014.75
71. Rollema, H. S., Kuipers, O. P., Both, P., de Vos, W. M., and Siezen, R. J. (1995). Improvement of solubility and stability of the antimicrobial peptide nisin by protein engineering. Appl. Environ. Microbiol. 61, 2873-2878.
72. Ross, A. C., McKinnie, S. M., and Vederas, J. C. (2012). The synthesis of active and stable diaminopimelate analogues of the lantibiotic peptide lactocin S. J. Am. Chem. Soc. 134, 2008-2011. doi: 10.1021/ja211088m
73. Rouse, S., Field, D., Daly, K. M., O'Connor, P. M., Cotter, P. D., Hill, C., et al. (2012). Bioengineered nisin derivatives with enhanced activity in complex matrices. Microb. Biotechnol. 5, 501-508. doi: 10.1111/j.1751-7915.2011.00324.x
74. Sahl, H., and Bierbaum, G. (2008). Multiple activities of natural agents such as defensins and bacteriocins suggest a change in strategy when developing new antimicrobials. Microbe 3, 467-473.
75. Saising, J., Dube, L., Ziebandt, A.-K., Voravuthikunchai, S. P., Nega, M., and Götz, F. (2012). Activity of Gallidermin on Staphylococcus aureus and Staphylococcus epidermidis Biofilms. Antimicrob. Agents Chemother. 56, 5804-5810. doi: 10.1128/AAC.01296-12
76. Sandiford, S. K. (2015). Perspectives on lantibiotic discovery-where have we failed and what improvements are required? Expert. Opin. Drug Discov. 10, 315-320. doi: 10.1517/17460441.2015.1016496
77. Severina, E., Severin, A., and Tomasz, A. (1998). Antibacterial efficacy of nisin against multidrug-resistant Gram-positive pathogens. J. Antimicrob. Chemother. 41, 341-347. doi: 10.1093/jac/41.3.341
78. Shi, Y., Bueno, A., and van der Donk, W. A. (2012). Heterologous production of the lantibiotic Ala(0)actagardine in Escherichia coli. Chem. Commun. (Camb) 48, 10966-10968. doi: 10.1039/c2cc36336d
79. Tabor, A. B. (2014). Recent advances in synthetic analogues of lantibiotics: what can we learn from these? Bioorg. Chem. 55, 39-50. doi: 10.1016/j.bioorg.2014.04.004
80. Tagg, J. R. (2004). Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Indian J. Med. Res. 119(Suppl.), 13-16.
81. van der Donk, W. A., and Nair, S. K. (2014). Structure and mechanism of lanthipeptide biosynthetic enzymes. Curr. Opin. Struct. Biol. 29, 58-66. doi: 10.1016/j.sbi.2014.09.006
82. Wescombe, P. A., Heng, N. C. K., Burton, J. P., Chilcott, C. N., and Tagg, J. R. (2009). Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics. Future Microbiol. 4, 819-835. doi: 10.2217/fmb.09.61
83. Wiedemann, I., Breukink, E., van Kraaij, C., Kuipers, O. P., Bierbaum, G., de Kruijff, B., et al. (2001). Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J. Biol. Chem. 276, 1772-1779. doi: 10.1074/jbc. M006770200
84. Willey, J. M., and Gaskell, A. A. (2011). Morphogenetic signaling molecules of the streptomycetes. Chem. Rev. 111, 174-187. doi: 10.1021/cr1000404
85. Willey, J. M., and van der Donk, W. A. (2007). Lantibiotics: peptides of diverse structure and function. Annu. Rev. Microbiol. 61, 477-501. doi: 10.1146/annurev.micro.61.080706.093501
86. Yuan, J., Zhang, Z. Z., Chen, X. Z., Yang, W., and Huan, L. D. (2004). Site-directed mutagenesis of the hinge region of nisinZ and properties of nisinZ mutants. Appl. Microbiol. Biotechnol. 64, 806-815. doi: 10.1007/s00253-004-1599-1