The Biological Origin: The Streptomyces Connection
Natamycin's fundamental composition is not from synthetic chemicals but from a biological process known as fermentation. It is classified as a secondary metabolite, a compound produced by certain microorganisms during their stationary phase of growth. The primary producers of natamycin are specific bacteria from the Streptomyces genus, which are commonly found in soil.
The discovery of natamycin traces back to 1955 when it was isolated from a soil sample collected in South Africa's Natal province. The producing organism was identified as Streptomyces natalensis, from which the name 'natamycin' was derived. Since its discovery, other related Streptomyces species have also been found to produce this compound, including S. chattanoogensis, S. gilvosporeus, and S. lydicus.
The Fermentation and Production Process
Commercial production of natamycin relies on a controlled fermentation process in industrial bioreactors. This involves cultivating the selected Streptomyces strain in a nutrient-rich medium under submerged aerobic conditions. The process includes several key stages:
- Inoculum preparation: A pure culture of a high-yielding Streptomyces strain is grown to a sufficient density to initiate the main fermentation.
- Fermentation: The inoculum is added to a large fermentation tank containing a liquid medium with carbon sources (like glucose or starch) and nitrogen sources (like soy meal or corn steep liquor). The culture is kept agitated and aerated to promote growth and natamycin production.
- Extraction: Since natamycin has very poor water solubility, it accumulates as solid crystals in the fermentation broth. It is then separated from the bacterial biomass through filtration or solvent extraction.
- Purification and Crystallization: The extracted natamycin is further purified to remove impurities. It is then concentrated and crystallized to achieve a high level of purity.
- Drying and Packaging: The final crystalline product is dried into a powder, which may then be mixed with excipients like lactose or glucose for standardization before packaging.
Chemical Composition and Structure
Chemically, natamycin is a polyene macrolide antibiotic, belonging to a large group of antifungal compounds.
- Chemical Formula: The empirical formula of natamycin is C₃₃H₄₇NO₁₃.
- Key Structural Components: Its structure is characterized by a macrocyclic lactone ring with a rigid, lipophilic chain containing four conjugated double bonds, making it a tetraene. It also has a mycosamine moiety, a six-membered pyranose ring with an amino group. The presence of both hydrophilic (hydroxyl and carboxylic acid) and hydrophobic regions makes it an amphoteric molecule.
This specific chemical structure is crucial for its function, allowing it to selectively target fungi by binding to ergosterol in their cell membranes, disrupting membrane integrity and causing cell death.
Applications in Medicine and Food
Natamycin's potent antifungal activity makes it valuable in both medicine and the food industry. In medicine, it is used topically, primarily as eye drops (under the trade name Natacyn), to treat fungal keratitis, a serious infection of the cornea. Its negligible absorption from the gastrointestinal tract means it is not effective for systemic fungal infections.
As a food additive (E235), natamycin acts as a biopreservative to inhibit the growth of yeasts and molds, thereby extending the shelf life of various food products. It is especially useful for foods that rely on bacterial cultures, as it has no activity against bacteria.
Natamycin vs. Other Preservatives: A Comparison
| Feature | Natamycin | Sorbic Acid (E200) | Nisin (E234) |
|---|---|---|---|
| Source | Produced by fermentation of Streptomyces bacteria | Synthetically produced or derived from natural sources (rowan berries) | Produced by fermentation of Lactococcus lactis bacteria |
| Target Micro-organisms | Yeasts and molds | Molds and yeasts, and some bacteria | Gram-positive bacteria, especially spores |
| Mechanism of Action | Binds to fungal cell membrane sterols | Disrupts cell membrane functions and enzyme activity in molds/yeasts | Disrupts bacterial cell membrane, forming pores and causing leakage |
| Primary Use | Surface treatment for cheese, sausages, and other dairy products | Wide range of applications including beverages, baked goods, and cheese | Canned goods, processed cheese, and other products requiring control of spoilage bacteria |
| Effect on Bacteria | No activity against bacteria; allows bacterial ripening | Some effect against certain bacteria | Highly effective against gram-positive bacteria |
Conclusion
In summary, natamycin is a sophisticated and highly specific antifungal agent whose composition is a direct result of the fermentation process carried out by soil-dwelling Streptomyces bacteria. Its identity as a polyene macrolide antibiotic, with a complex chemical structure, is what enables it to selectively target fungal pathogens while leaving beneficial bacteria unaffected. From its biological origins in South African soil to its controlled industrial production, natamycin's journey underscores the power of microbial biotechnology in creating effective solutions for both medical and food preservation applications. For more information on its use as a food additive, the U.S. Food and Drug Administration (FDA) provides regulatory guidance.
