Optimization of Media to Improve Macrolide Antibiotic Production while Minimizing Impurities

Abstract

Immunomycin is a fermentation product of Streptomyces hygroscopicus var ascomycetes. Macrolide produced from Streptomyces hygroscopicus has superior activity when compared to cyclosporine. The immunosuppressant activity is useful in treatment of autoimmune diseases, as well as infectious diseases. The serious side effects of cyclosporine treatment include kidney failure, liver damage and ulcers, so there is a need for new safer and more effective method of treatment. The present study was carried out in order to get higher titer of macrolide in fermentation. The microbial fermentation of streptomyces hygroscopicus produces two different types of compounds, i.e., FK-520 and FK-523. The presence of FK-523 is undesirable because it has less immunosuppressive activity when compared to FK-520, so this was considered as an impurity. The main purpose of the experiment was to decrease the impurity percentage whereas increasing the titer of desired product. Optimization of carbon source has an impact on product titer and impurity percentage. DMH is the conventionally used carbon source for fermentation of streptomyces sp., comparing the activity of DMH with 80 g/L potato starch. Potato starch has given higher product activity of 2.692 mg/mL. Whereas DMH was 1.410 mg/mL, the respective impurity levels were 4.42% and 9.690%. There was 190% increase in product titer and 50% decrease in impurity with 80 g/L potato starch compared to DMH. This decrease in impurity percentage is not catalyzed by any addition of components like crotonic acid.