Nisin
Nisin is a lantibiotic peptide produced by Lactococcus lactis, used as a food preservative since 1969, that kills gram-positive bacteria by binding lipid II and forming pores.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C143H228N42O37S7 |
| Molecular Weight | 3354.07 g/mol |
| CAS Number | 1414-45-5 |
| IUPAC Name | Nisin A (lantibiotic) |
| Peptide Class | Lantibiotic (Class I bacteriocin) |
| Origin | Lactococcus lactis |
Structure
Nisin is a 34-amino acid lantibiotic peptide containing five thioether bridges (lanthionine and methyllanthionine rings) formed by post-translational modification of serine/threonine and cysteine residues. These unusual amino acids create five interconnected rings (A-E) that stabilize the peptide’s structure. Nisin contains dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues, which contribute to its unusual chemical properties.
Mechanism of Action
Nisin has a unique dual mechanism of action:
- Lipid II binding: The N-terminal ring A binds with high affinity to lipid II (undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide), the essential peptidoglycan precursor
- Pore formation: Multiple nisin-lipid II complexes oligomerize to form large transmembrane pores (2-2.5 nm diameter)
- Cell wall inhibition: Lipid II sequestration blocks both peptidoglycan synthesis and membrane integrity
This dual targeting makes spontaneous resistance to nisin extremely rare. The binding to lipid II is similar to vancomycin but occurs through a completely different mechanism.
Applications
Nisin has been used globally as a food preservative (E234) since 1969:
- Food preservation: Approved in over 50 countries for dairy products, canned foods, and processed meats
- Anti-listeria: Effective against Listeria monocytogenes in ready-to-eat foods
- Medical applications: Under investigation for topical anti-infective applications, dental caries prevention, and anti-biofilm coatings
- Agriculture: Investigated as an alternative to antibiotics in animal husbandry
Pharmacokinetics
- Stability: Active at acidic to neutral pH; degraded at alkaline pH
- Proteolysis: Rapidly degraded by trypsin and chymotrypsin in the GI tract
- Bioavailability: Minimal systemic absorption when ingested
- Thermal stability: Stable to moderate heat treatment; activity retained after pasteurization
Safety and Side Effects
Nisin has an extensive safety record as a food additive, with no significant adverse effects reported in over 50 years of use. GRAS (Generally Recognized As Safe) status in the US. No allergenic potential detected. Extremely low oral toxicity (LD50 > 7000 mg/kg in rats). Not associated with cross-resistance to clinical antibiotics.
References
- Cotter, P.D., et al. (2013). Bacteriostatic and bactericidal lantibiotics. Nature Reviews Microbiology, 11, 596-607.
- Breukink, E., et al. (1999). The antibiotic nisin targets lipid II. Science, 286, 2361-2364.
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