
What is Nisin?
  Nisin is a natural antimicrobial agent used  as a preservative in heat processed and low pH foods. The nisin preparation is  a concentrate of dry material derived from the controlled fermentation of a  naturally occurring Streptococcus lactis.  This bacterium contains nisin, a group of related peptides (partial amino acid  chains that make up proteins) with antibiotic activity. The chemical nisin  cannot be synthesized artificially, so the nisin-producing bacteria are  basically farmed for their synthesis of nisin. 
  How is it made?
  Technical specifications for   nisin  indicate that the process begins by fermenting the milk bacteria.  The resulting nisin is concentrated, separated, and dried before milling into  fine particles and standardized by the addition of sodium chloride (salt). The  resulting typical composition is nisin (2.5%), sodium chloride (greater than  50%) , protein (23.8%), and moisture (less than 3%). 
  Is it safe? 
  Nisin is listed as a "natural  preservative" in chemical dictionaries. In addition,  nisin as  "replacement or partial replacement of chemical preservatives." Nisin  was awarded the Generally Regarded as Safe (GRAS) designation in the U.S.  Federal Register of April, 1988 and is approved as a natural food preservative  in the United States. It is also approved as a natural food preservative by  more than 60 other countries as well as with the Food and Agriculture  Organization/World Health Organization and the European Union. The Nisaplin  brand of nisin is certified kosher, as well. 
  Use and limitations: 
  In the U.S., nisin is used to inhibit  outgrowth of Clostridium botulinum spores (the cause of botulism) and toxin  formation in pasteurized process cheese spreads with fruits, vegetables or  meats at levels not exceeding good manufacturing practice. Current good  manufacturing practice in this case is the quantity of the ingredient that  delivers a maximum of 250 p.p.m. of nisin in the finished product.  nisin  is also approved for liquid egg products, dressings, and sauces. In other  countries it is also used in fresh and recombined milk, fermented beverages  like beer, canned foods, frozen desserts, and high moisture/reduced fat foods. 
  Nisin is considered effective at controlling  a wide range of gram-positive organisms including: Listeria, enterococcus,  Bacillus sporothermodurans, and clostridium. Used alone, it is not effective on  gram-negative bacteria (like E coli ), yeasts, and molds. However, research  suggests that it may be useful against some gram-negative bacteria when used in  conjunction with other preservatives. 
In conclusion-based on the way it is  manufactured, its GRAS status, and its "natural" labeling  designation-nisin appears to qualify as a safe and natural food preservative.
Two natural nisin molecules exist, termed nisin A and nisin Z. The structure of the nisin A molecule was elucidated in 1971. It is a 34-amino-acid polypeptide with amino and carboxyl endgroups, and five internal ring structures involving disulfide bridges. It possesses three unusual amino acids: dehydroalanine, lanthionine, and β-methyllanthionine. Lanthionine appears to be a common feature in a number of more recently characterized bacteriocins that are collectively known as lantibiotics. Nisin Z differs from nisin A by the substitution of asparagine for histidine at position 27. Nisin Z has a similar antimicrobial activity to nisin A, although nisin Z shows greater diffusion in agar gels. Nisin A has a molecular weight of 3354 Da. There is evidence that nisin can exist as both dimers and tetramers.
Nisin applied to Alcoholic Beverages J. Delves-Broughton, in Encyclopedia of Food Microbiology (Second Edition, 2014Nisin has a potential role in the production of alcoholic beverages. It has been demonstrated that nisin is effective in controlling spoilage by lactic acid bacteria, such as Lactobacillus, Pediococcus, Leuconostoc, and Oenococcus at a level of 0.25–2.5 mg l−1 in both beer and wine. Yeasts are completely unaffected by nisin, which allows its addition during the fermentation. Identified applications of nisin in the brewing and wine industry include: its addition to fermenters to prevent or control contamination, increasing the shelf life of unpasteurized beers, reducing pasteurization regimes, and washing pitching yeast to eliminate contaminating bacteria (as an alternative method to acid washing, which affects yeast viability). Formerly, nisin could not be used during wine fermentations that depend on malolactic acid fermentation. However, this problem has been overcome by developing nisin-resistant strains of Oenococcus oenos, which can grow and maintain malolactic fermentation in the presence of nisin. In the production of fruit brandies, the addition of nisin reduces the growth of competitive lactic acid bacteria and directly favors the growth of the fermenting yeast, to increase alcohol content by at least 10%.
Potential in Food PreservationDairy Products
  Nisin is used in pasteurized, processed  cheese products to prevent outgrowth of spores such as those of Clostridium  tyrobutyricum that may survive heat treatments as high as 85–105°C. Use of  nisin allows these products to be formulated with high moisture levels and low  NaCl and phosphate contents, and also allows them to be stored outside chill  cabinets without risk of spoilage. The level of nisin used depends on food  composition, likely spore load, required shelf life and temperatures likely to  be encountered during storage.
  Nisin is also used to extend the shelf life  of dairy desserts which cannot be fully sterilized without damaging appearance,  taste or texture. Nisin can significantly increase the limited shelf life of  such pasteurized products.
  Nisin is added to milk in the Middle East  where shelf-life problems occur owing to the warm climate, the necessity to  transport milk over long distances and poor refrigeration facilities. It can  double the shelf life at chilled, ambient and elevated temperatures and prevent  outgrowth of thermophilic heat-resistant spores that can survive  pasteurization. It can also be used in canned evaporated milk.
M. Mastromatteo, ... M.A. Del Nobile, in Encyclopedia of Food Microbiology (Second Edition), 2014
Direct Incorporation of Bacteriocins  into/onto the Polymeric Film
  Nisin received considerable attention in  the food packaging sector, being the sole purified antimicrobial peptide  approved by the US Food and Drug Administration. Nisin was incorporated into a  polyethylene-based plastic film that was used to vacuum-package beef carcasses.  Nisin retained activity against Lactobacillus helveticus and Brochothrix  thermosphacta inoculated in carcass surface tissue sections. Nisin was also  incorporated in films made up of hydroxy-propyl-methyl-cellulose. Inhibitory  effect has been demonstrated against L. innocua and St. aureus, but film additives  such as stearic acid, used to improve the water vapor barrier properties of the  film, significantly reduced the inhibitory activity. Nisin, lauric acid, and  ethylenediamine tetraacetic acid (EDTA) were included in corn zein films and  then exposed to broth cultures of Salmonella enteritidis. None of the  combinations produced reductions of the pathogen greater than 1 log CFU ml−1.  In contrast, the use of edible films with nisin, EDTA, citric acid, and Tween  80 was evaluated on Salmonella typhimurium in poultry skin. Nisin is inactive  against yeast, molds, and Gram-negative bacteria. This partial success of nisin  as a natural food preservative has prompted examination of other bacteriocins.  Bacteriocins in general should not be used as the main processing step to  prevent the growth or survival of pathogens but to provide an additional hurdle  to reduce the likelihood of foodborne disease. The combination of  antimicrobials with other inhibitory treatments such as high hydrostatic  pressure treatment has been proposed to achieve a high inactivation of  Gram-negative foodborne pathogens. Natamycin is commonly used as an antifungal  agent for cheese and sausages. Natamycin-impregnated cellulose films showed  inhibitory effect against P. roquefortii on Gorgonzola cheese. Combination of  nisin and natamycin in cellulose film prolonged the shelf life of sliced  mozzarella cheese by 6 days. In contrast, methyl-cellulose and wheat gluten  films containing natamycin did not cause any significant decrease of P.  roquefortii on cheese surface. The bilayer coating of chitosan and polyethylene  wax microemulsion, including natamycin, demonstrated an inhibitory effect  against two pathogenic fungi during storage of melon.
