Natamycin

Natamycin

Clinical data
ATC code	A01AB10 (WHO) A07AA03 (WHO), D01AA02 (WHO), G01AA02 (WHO), S01AA10 (WHO)
Identifiers
IUPAC name (1R,3S,5R,7R,8E,12R,14E,16E,18E,20E,22R,24S,25R,26S)-22-[(3-amino-3,6-dideoxy-D-mannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.05,7]octacosa-8,14,16,18,20-pentaene-25-carboxylic acid
CAS Number	7681-93-8
PubChem CID	441382
DrugBank	APRD01136
E number	E235 (preservatives)
CompTox Dashboard (EPA)	DTXSID6021163
ECHA InfoCard	100.028.803
Chemical and physical data
Formula	C33H47NO13
Molar mass	665.725 g/mol g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)[C@@H]3[C@@H](O)C[C@@]2(O)C[C@@H](O)C[C@H]4O[C@@H]4C=CC(=O)O[C@H](C)CC=CC=CC=CC=C[C@H](OC1O[C@H](C)[C@@H](O)[C@H](N)[C@@H]1O)C[C@@H]3O2

Natamycin (INN), also known as pimaricin, is a naturally occurring antifungal agent produced during fermentation by the bacterium Streptomyces natalensis, commonly found in soil. Natamycin has a very low solubility in water, due to the amphiphilic nature of the molecule. However, natamycin is effective at very low levels. Most Molds have an MIC (Minimum inhibitory concentration) of <10ppm. Natamycin is classified as a macrolide polyene antifungal and, as a drug, is used to treat fungal keratitis. It is especially effective against Aspergillus and Fusarium corneal infections. Other common members of the polyene macrolide antifungal family are Amphotericin B, Nystatin, and Filipin.

Uses

In foods

Natamycin has been used for decades in the food industry as a hurdle to fungal outgrowth in dairy products, meats, and other foods. Potential advantages for the usage of natamycin might include the replacement of traditional chemical preservatives, a neutral flavor impact, and less dependence on pH for efficacy, as is common with chemical preservatives. It may be applied by spraying a liquid suspension, by dipping the product in an aqueous suspension (known as a "brine"), or by mixing it into the product in a powdered form along with cellulose (a known "anti-caking" agent) on whole, shredded, or soft cheeses. While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Also, natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cottage cheese, sour cream, and yogurt. As a food additive, it has E number E235.
Throughout the European Union, it is only approved as a surface preservative for certain cheese and dried sausage products. The EU Scientific Comitee on Food (SCF) states on the usage of Natamycin: "However, in view of the general principle with regard to the undesirability of using antibiotics in foodstuffs the Committee is strongly opposed to proposals for further food uses of natamycin such as use on ham and wine and other beverages." (SCF, 1979)

Medical

Natamycin is used to treat fungal infections, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. It is applied as a cream, in eyedrops, or (for oral infections) in a lozenge. Natamycin shows negligible absorption into the body when administered in these ways. When taken orally, little or none is absorbed from the gastrointestinal tract, making it inappropriate for systemic infections.

Safety

Natamycin lacks acute toxicity. In animal studies, the lowest LD₅₀ found was 450 mg/kg. In rats, the LD₅₀ is ≥2300 mg/kg, and doses of 500 mg/kg/day over 2 years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD₅₀ than natamycin, but in all cases the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea.

There is no evidence that natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available.