Advertisement

Applied Microbiology and Biotechnology

, Volume 102, Issue 15, pp 6299–6307 | Cite as

Innovative approaches to nisin production

  • Burcu Özel
  • Ömer Şimşek
  • Mustafa Akçelik
  • Per E. J. Saris
Mini-Review

Abstract

Nisin is a bacteriocin produced by Lactococcus lactis that has been approved by the Food Drug Administration for utilization as a GRAS status food additive. Nisin can inhibit spore germination and demonstrates antimicrobial activity against Listeria, Clostridium, Staphylococcus, and Bacillus species. Under some circumstances, it plays an immune modulator role and has a selective cytotoxic effect against cancer cells, although it is notable that the high production cost of nisin—a result of the low nisin production yield of producer strains—is an important factor restricting intensive use. In recent years, production of nisin has been significantly improved through genetic modifications to nisin producer strains and through innovative applications in the fermentation process. Recently, 15,400 IU ml−1 nisin production has been achieved in L. lactis cells following genetic modifications by eliminating the factors that negatively affect nisin biosynthesis or by increasing the cell density of the producing strains in the fermentation medium. In this review, innovative approaches related to cell and fermentation systems aimed at increasing nisin production are discussed and interpreted, with a view to increasing industrial nisin production.

Keywords

Nisin Innovative system Fermentation Bacteriocin 

Notes

Funding

This research was supported by the Scientific and Technological Research Council of Turkey (TUBİTAK) with grant numbers 109O589 and 112O497.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not involve any studies with human participants involving any of the authors.

References

  1. Amiali MN, Lacroix C, Simard RE (1998) High nisin Z production by Lactococcus lactis UL719 in whey permeate with aeration. World J Microbiol Biotechnol 14:887–894CrossRefGoogle Scholar
  2. Ariana M, Hamedi J (2017) Enhanced production of nisin by co-culture of Lactococcus lactis subsp. lactis and Yarrowia lipolytica in molasses based medium. J Biotechnol 256:21–26.  https://doi.org/10.1016/j.jbiotec.2017.07.009 CrossRefPubMedGoogle Scholar
  3. Belfiore C, Castellano P, Vignolo G (2007) Reduction of Escherichia coli population following treatment with bacteriocins from lactic acid bacteria and chelators. Food Microbiol 24:223–229.  https://doi.org/10.1016/j.fm.2006.05.006 CrossRefPubMedGoogle Scholar
  4. Bertrand N, Fliss I, Lacroix C (2001) High nisin-Z production during repeated-cycle batch cultures in supplemented whey permeate using immobilized Lactococcus lactis UL719. Int Dairy J 11(12):953–960.  https://doi.org/10.1016/S0958-6946(01)00129-7 CrossRefGoogle Scholar
  5. Bolotin A, Mauger S, Malarme K, Ehrlich SD, Sorokin A (1999) Low redundancy sequencing of the entire Lactococcus lactis IL1403 genome. Antonie Van Leeuwenhoek 76:27–76CrossRefPubMedGoogle Scholar
  6. Brooijmans RJ, Smit B, Santos F, Riel JV, Vos W, Hugenholtz J (2009) Heme and menaquinone induced electron transport in lactic acid bacteria. Microb Cell Factories 8:1475–1486.  https://doi.org/10.1186/1475-2859-8-28 CrossRefGoogle Scholar
  7. Bryan-Jones DG, Whittenbury R (1969) Haematin-dependent oxidative phosphorylation in Streptococcus faecalis. J Gen Microbiol 58:247–260.  https://doi.org/10.1099/00221287-58-2-247 CrossRefPubMedGoogle Scholar
  8. Buchman GW, Banerjee S, Hansen JN (1988) Structure, expression and evolution of a gene encoding the precursor of nisin, a small protein antibiotic. J Biol Chem 263(31):16260–16266PubMedGoogle Scholar
  9. Cabo ML, Murado MA, Gonzalez MP, Vazquez JA, Pastoriza L (2001) An empirical model for describing the effects of nitrogen sources on nisin production. Lett Appl Microbiol 33(6):425–429.  https://doi.org/10.1046/j.1472-765X.2001.01020.x CrossRefPubMedGoogle Scholar
  10. Chandrapati S, O'Sullivan DJ (1999) Nisin independent induction of the nisA promoter in Lactococcus lactis during growth in lactose or galactose. FEMS Microbiol Lett 170(1):191–198.  https://doi.org/10.1111/j.1574-6968.1999.tb13374.x CrossRefPubMedGoogle Scholar
  11. Cheigh CI, Choi HJ, Park H, Kim S, Kook M, Kim T, Hwang J, Pyun Y (2002) Influence of growth conditions on the production of a nisin-like bacteriocin by Lactococcus lactis subsp. lactis A164 isolated from kimchi. J Biotechnol 95:225–235.  https://doi.org/10.1016/S0168-1656(02)00010-X CrossRefPubMedGoogle Scholar
  12. de Vuyst L, Vandamme EJ (1992) Influence of the carbon source on nisin production in Lactococcus lactis subsp. lactis batch fermentations. J Gen Microbiol 138:571–578.  https://doi.org/10.1099/00221287-138-3-571 CrossRefPubMedGoogle Scholar
  13. Engelke G, Gutowski-Eckel Z, Hammelman M, Entian KD (1992) Biosynthesis of the lantibiotic nisin genomic organization and membrane localization of the NisB protein. Appl Environ Microbiol 58:3730–3743PubMedPubMedCentralGoogle Scholar
  14. Gharsallaoui A, Oulahal N, Joly C, Degraeve P (2016) Nisin as a food preservative: part 1: physicochemical properties, antimicrobial activity, and main uses. Crit Rev Food Sci Nutr 56:1262–1274.  https://doi.org/10.1080/10408398.2013.763765 CrossRefPubMedGoogle Scholar
  15. Graeffe T, Rintala H, Paulin L, Saris P (1991) A natural nisin variant. In Nisin and novel lantibiotics. Sci Publishers 260–268Google Scholar
  16. Gross E, Morell JL (1971) The structure of nisin. J Am Chem Soc 93:4634–4635CrossRefPubMedGoogle Scholar
  17. Hao P, Liang D, Cao L, Qiao B, Wu H, Caiyin Q, Zhu H, Qiao J (2017) Promoting acid resistance and nisin yield of Lactococcus lactis F44 by genetically increasing D-Asp amidation level inside cell wall. Appl Microbiol Biotechnol 101:6137–6153.  https://doi.org/10.1007/s00253-017-8365-7 CrossRefPubMedGoogle Scholar
  18. Hurst A (1981) Nisin. Adv Appl Microbiol 27:85–123CrossRefGoogle Scholar
  19. Jiang L, Liu Y, Yan G, Cui Y, Cheng Q, Zhang Z, Meng Q, Teng L, Ren X (2015) Aeration and fermentation strategies on nisin production. Biotechnol Lett 37:2039–2045.  https://doi.org/10.1007/s10529-015-1886-1 CrossRefPubMedGoogle Scholar
  20. Kim WS, Hall RJ, Dunn NW (1998) Improving nisin production by increasing immunity/resistance genes in the producer organism Lactococcus lactis. Appl Microbiol 50(4):429–433.  https://doi.org/10.1007/s002530051316 CrossRefGoogle Scholar
  21. Kong W, Lu T (2014) Cloning and optimization of a nisin biosynthesis pathway for bacteriocin harvest. ACS Synth Biol 3(7):439–445.  https://doi.org/10.1021/sb500225r CrossRefPubMedGoogle Scholar
  22. Kordikanlioglu B, Simsek O, Saris PE (2015) Nisin production of Lactococcus lactis N8 with hemin-stimulated cell respiration in fed-batch fermentation system. Biotechnol Prog 31(3):678–685.  https://doi.org/10.1002/btpr.2075 CrossRefPubMedGoogle Scholar
  23. Kuipers OP, Beerthuyzen MM, de Ruyter PGGA, Luesink EJ, de Vos WM (1995) Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J Biol Chem 270:27299–27304.  https://doi.org/10.1074/jbc.270.45.27299 CrossRefPubMedGoogle Scholar
  24. Kwaadsteniet M, Doeschate K, Dicks LMT (2008) Characterization of the structural gene encoding nisin F, a new lantibiotic produced by a Lactococcus lactis subsp. lactis isolate from freshwater catfish (Clarias gariepinus). Appl Environ Microbiol 74:547–549.  https://doi.org/10.1128/AEM.01862-07
  25. Lechardeur D, Cesselin B, Fernandez A, Lamberet G, Garrigues C, Pedersen M, Lv W, Cong W, Cai Z (2004) Nisin production by Lactococcus lactis subsp. lactis under nutritional limitation in fed-batch culture. Biotechnol Lett 26:235–238.  https://doi.org/10.1023/B:BILE.0000013721.78288.1 CrossRefGoogle Scholar
  26. Liu J, Maa Z, Zhua H, Caiyina Q, Lianga D, Wua H, Huangd X, Qiaoa J (2017) Improving xylose utilization of defatted rice bran for nisin production by overexpression of a xylose transcriptional regulator in Lactococcus lactis. Bioresour Technol 238:690–697.  https://doi.org/10.1016/j.biortech.2017.04.076 CrossRefPubMedGoogle Scholar
  27. Luck E, Jager M (1995) Nisin. Antimicrobial Food Addit 27:208–213Google Scholar
  28. Malvido C, González A, Guerra P (2016) Nisin production in realkalized fed-batch cultures in whey with feeding with lactose- or glucose-containing substrates. Appl Microbiol Biotechnol 100(18):7899–7908.  https://doi.org/10.1007/s00253-016-7558-9 CrossRefGoogle Scholar
  29. Mulders JWM, Boerrigter IJ, Rollema HS, Siezen RJ, de Vos WM (1991) Identification and characterization of the lantibiotic nisin Z, a natural nisin variant. Eur J Biochem 201:581–584.  https://doi.org/10.1111/j.1432-1033.1991.tb16317.x CrossRefPubMedGoogle Scholar
  30. Ni Z, Zhang X, Liu F, Wang M, Hao R, Ling P, Zhu X (2017) Effect of co-overexpression of nisin key genes on nisin production improvement in Lactococcus lactis LS01. Probiotics Antimicrob Protein 9(2):204–212.  https://doi.org/10.1007/s12602-017-9268-8 CrossRefGoogle Scholar
  31. O’Connor PM, O’Shea EF, Guinane CM, O’Sullivan O, Cotter PD, Ross RP, Hill C (2015) Nisin H is a new nisin variant produced by the gut-derived strain Streptococcus hyointestinalis. Appl Environ Microbiol 81(12):3953–3960.  https://doi.org/10.1128/AEM.00212-15 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Papagianni M, Avramidis N (2012) Engineering the central pathways in Lactococcus lactis: functional expression of the phosphofructokinase (pfk) and alternative oxidase (aox1) genes from Aspergillus niger in Lactococcus lactis facilitates improved carbon conversion rates under oxidizing conditions. Enzym Microbiol Technol 51(3):125–130.  https://doi.org/10.1016/j.enzmictec.2012.04.007 CrossRefGoogle Scholar
  33. Patent (1960) Production of nisin, Patented by United States Patent Office with number US2935503Google Scholar
  34. Pedersen M, Gaudu P, Lechardeur D, Petit M, Gruss A (2012) Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology. Annu Rev Food Sci Technol 3:37–58.  https://doi.org/10.1146/annurev-food-022811-101255 CrossRefPubMedGoogle Scholar
  35. Pongtharangkul T, Demirci A (2006) Evaluation of culture medium for nisin production in a repeated-batch biofilm reactor. Biotechnol Prog 22:217–224.  https://doi.org/10.1021/bp050295q CrossRefPubMedGoogle Scholar
  36. Ra R, Qiao M, Immonen T, Pujana I, Saris PEJ (1996) Genes responsible for nisin synthesis, regulation and immunity form a regulon of two operons and are induced by nisin in Lactococcus lactis N8. Microbiology 142:1281–1288.  https://doi.org/10.1099/13500872-142-5-1281 CrossRefPubMedGoogle Scholar
  37. Ra R, Saris PEJ (1995) Characterization of procaryotic mRNAs by RT-PCR. Biotechniques 18:792–795Google Scholar
  38. Rezaiki L, Cesselin B, Yamamato Y, Vido K, van West E, Gaudu P, Gruss A (2004) Respiration metabolism reduces oxidative and acid stress to improve long-term survival of Lactococcus lactis. Mol Biol 53(5):1331–1342.  https://doi.org/10.1111/j.1365-2958.2004.04217.x CrossRefGoogle Scholar
  39. Sijpestejn AK (1970) Induction of cytochrome formation and stimulation of oxidative dissimilation by hemin in Streptococcus lactis and Leuconostoc mesenteroides. Antonie Van Leeuwenhoek 36:335–348CrossRefGoogle Scholar
  40. Simsek O (2014) Nisin production in a chitin-including continuous fermentation system with Lactococcus lactis displaying a cell wall chitin-binding domain. J Ind Microbiol Biotechnol 41:535–543.  https://doi.org/10.1007/s10295-013-1388-x CrossRefPubMedGoogle Scholar
  41. Simsek O, Saris PEJ (2009) Cycle changing the medium results in increased nisin productivity per cell in Lactococcus lactis. Biotechnol Lett 31(3):415–421.  https://doi.org/10.1007/s10529-008-9891-2 CrossRefPubMedGoogle Scholar
  42. Simsek O, Akkoc N, Con AH, Ozcelik F, Saris PEJ, Akcelik M (2009a) Continuous nisin production with bioengineered Lactococcus lactis strains. J Ind Microbiol Biotechnol 36(6):863–871.  https://doi.org/10.1007/s10295-009-0563-6 CrossRefPubMedGoogle Scholar
  43. Simsek O, Con AH, Akkoc N, Saris PEJ, Akcelik M (2009b) Influence of growth conditions on the nisin production of bioengineered Lactococcus lactis strains. J Ind Microbiol Biotechnol 36:481–490.  https://doi.org/10.1007/s10295-008-0517-4 CrossRefPubMedGoogle Scholar
  44. Stein T, Heinzmann S, Solovieva I, Entian KD (2003) Function of Lactococcus lactis nisin immunity genes nisI and nisFEG after coordinated expression in the surrogate host Bacillus subtilis. J Biol Chem 278(1):89–94.  https://doi.org/10.1074/jbc.M207237200 CrossRefPubMedGoogle Scholar
  45. Takala TM, Saris PEJ (2007) Nisin: past, present and future. In: Riley MA, Gillor O (eds) Research and applications of bacteriocins. Horizon Bioscience, pp 181–213Google Scholar
  46. Tramer J, Fowler GG (1964) Estimation of nisin in foods. J Sci Food Agric 15:522–528CrossRefGoogle Scholar
  47. Wardani AK, Egawa S, Nagahisa K, Shimizu H, Shioya S (2006) Robustness of cascade pH and dissolved oxygen control in symbiotic nisin production process system of Lactococcus lactis and Kluyveromyces marxianus. J Biosci Bioeng 101(3):274–276.  https://doi.org/10.1263/jbb.101.274 CrossRefPubMedGoogle Scholar
  48. Whittenbury R (1978) Biochemical characteristics of Streptococcus species. Soc Appl Bacteriol Symp Ser 7:51–69PubMedGoogle Scholar
  49. Wirawan RE, Klesse NA, Jack RW, Tagg JR (2006) Molecular and genetic characterization of a novel nisin variant produced by Streptococcus uberis. Appl Environ Microbiol 72:1148–1156. https://doi.org/10.1128%2FAEM.72.2.1148-1156.2006Google Scholar
  50. Zendo T, Fukao M, Ueda K, Higuchi T, Nakayama J, Sonomoto K (2003) Identification of the lantibiotic nisin Q, a new natural nisin variant produced by Lactococcus lactis 61-14 isolated from a river in Japan. Biosci Biotechnol Biochem 67:1616–1619.  https://doi.org/10.1271/bbb.67.1616 CrossRefPubMedGoogle Scholar
  51. Zhang YF, Liu SY, Du YH, Feng WJ, Liu JH, Qiao JJ (2014) Genome shuffling of Lactococcus lactis subspecies lactis YF11 for improving nisin Z production and comparative analysis. J Dairy Sci 97(5):2528–2541.  https://doi.org/10.3168/jds.2013-7238 CrossRefPubMedGoogle Scholar
  52. Zhang J, Caiyin Q, Feng W, Zhao X, Qiao B, Zhao G, Qiao J (2016) Enhance nisin yield via improving acid-tolerant capability of Lactococcus lactis F44. Sci Rep 6:27973.  https://doi.org/10.1038/srep27973 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Zheng H, Zhang D, Guo K, Dong K, Xu D, Wu Z (2015) Online recovery of nisin during fermentation coupling with foam fractionation. J Food Eng 162:25–30.  https://doi.org/10.1016/j.jfoodeng.2015.04.006 CrossRefGoogle Scholar
  54. Zhu D, Zhao K, Xu H, Bai U, Zhang X, Qiao M (2015) Effect of 6-phosphofructokinase gene-pfk overexpression on nisin production in Lactococcus lactis N8. Acta Microbiol Sin 55(4):440–447Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Burcu Özel
    • 1
  • Ömer Şimşek
    • 2
  • Mustafa Akçelik
    • 3
  • Per E. J. Saris
    • 4
  1. 1.Cal Vocational High School, Department of Food ProcessingUniversity of PamukkaleDenizliTurkey
  2. 2.Department of Food EngineeringUniversity of PamukkaleDenizliTurkey
  3. 3.Department of BiologyUniversity of AnkaraAnkaraTurkey
  4. 4.Department of MicrobiologyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations