Fermentation for Anthelmintic Agents

Parasitic worms include flat worms, such as flukes and tapeworms, and round worms, known as nematodes. Parasitic worms can infect livestock animals and domestic pets, and the parasitic load in animals make them debilitated and bad looking. Parasitic infections in lactating animals usually reduce milk production. Therefore, anthelmintic reagents are in high demand for long-acting, broad spectra anthelmintic treatments.

Fig 1. Illustration of four different mechanisms of action by anthelmintic agent against GI parasites. (Abdullah, M. M.; et al. 2022)

Fermentation Techniques in Anthelmintic Agents Production

The avermectins are complexes of chemically related agents with very effective anthelmintic activity. It is a new class of 16-membered ring macrolide antibiotics that not only exhibit excellent anthelmintic activity against nematode and arthropod parasites, but also have low toxic effects on host organisms. Avermectin and its analogs are produced by fermentation process via using a gram-positive bacterium called Streptomyces avermitilis. Increasing the production of avermectin is a major challenge of commercial importance in the veterinary market. There are three conventional methods to improve the fermentation efficiency of avermectin:

• Utilization of mutagens (e.g. UV, atmospheric pressure cold plasma, lithium chloride and nitrosoguanidine)
• Genetic engineering techniques
• Optimization of fermentation conditions including medium modification and strain selection

In addition to avermectins, there is another novel macrolide that is also manufactured by fermentation of a Streptomyces strain, which is produced by fusing a strain of Streptomyces avermitilis and Streptomyces hygroscopicus. The final fermented anti-parasitic and insecticidal compositions, particularly for anthelmintic and nematicidal use, can be obtained by being recovered and purified from the fermentation broth.

Fig 2. Fermentation and bottle fermentation. (Callejo, M. J.; et al. 2017)

Anthelmintic Fermentation Products Manufacturing

• Fermentation temperature: The fermentation is conducted at a temperature ranging from about 20℃ to about 40℃.
• The pH of the nutrient medium: Generally controlled between 5.0 and 8.5.
• Carbon source: Carbohydrates such as sugars, e.g. glucose, sucrose, maltose, lactose, dextran, cerelose, corn meal, oat flour, and the like, and starches are suitable sources of assimilable carbon in the nutrient media.
• Nitrogen sources: Yeast hydrolysate, yeast autolysate, yeast cells, tomato paste, corn meal, oat flour, soybean meal, casein hydrolysates, yeast extracts, corn steep liquors, distillers solubles, cottonseed meal, meat extract, etc., all of which are readily assimilated by the strain. The various sources of nitrogen can be used individually or in combination.
• Other substances in the medium: Among the nutritional inorganic salts that can be incorporated into the media are some conventional salts capable of producing sodium, potassium, magnesium, ammonium, calcium, phosphate, sulfate, chloride, and carbonate plasma. Also included are trace metals, such as cobalt and manganese.
• For larger-scale manufacturing work, fermentation is preferably carried out in suitable tanks equipped with agitators and aeration devices for the fermentation media.
• Separation and recovery: The separation and recovery of the final fermentated products from the whole fermentation broth is carried out by solvent extraction and application of chromatographic fractionation with various chromatographic techniques and solvent systems.
• Product structure identification: The presence of compounds is determined by analyzing the various chromatographic fractions for biological activity against selected parasites, or physicochemical properties. The structure is determined by detailed analysis of various spectral properties of the compounds, particularly their NMR, mass, UV and IR spectra.

Our Services

• Fermentation CDMO Service
• Strain Development Service
• Fermentation Process Optimization
• Fermentation for Special Small Molecules
• GRAS Services

BOC Sciences provides fermentation CDMO service for anthelmintic agents. With our complete quality management system and strong fermentation capabilities, we are able to help customers facilitate their fermentation related projects and support them from laboratory to commercialization.

Workflow of Our Service

References

1. Abdullah, M. M.; et al. Anthelmintic Drug Resistance in Livestock: Current Understanding and Future Trends. Parasitic Helminths and Zoonoses. 2022.
2. Callejo, M. J.; et al. Use of Non-Saccharomyces Yeasts in Bottle Fermentation of Aged Beers. Brewing Technology. 2017. 102-119.