Innovative approaches to nisin production
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.
KeywordsNisin Innovative system Fermentation Bacteriocin
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.
This article does not involve any studies with human participants involving any of the authors.
- 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
- 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
- Graeffe T, Rintala H, Paulin L, Saris P (1991) A natural nisin variant. In Nisin and novel lantibiotics. Sci Publishers 260–268Google Scholar
- 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
- 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
- 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
- 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
- Luck E, Jager M (1995) Nisin. Antimicrobial Food Addit 27:208–213Google Scholar
- 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
- 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
- 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
- Patent (1960) Production of nisin, Patented by United States Patent Office with number US2935503Google Scholar
- 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
- Ra R, Saris PEJ (1995) Characterization of procaryotic mRNAs by RT-PCR. Biotechniques 18:792–795Google Scholar
- 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
- 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
- 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
- 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
- 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