A combined statistical approach of orthogonal design and polynomial regression were applied to optimize the composition and concentration of a liquid fermentation medium for the production of bleomycin (BLM) by Streptomyces mobaraensis. Optimal conditions for maximal productivity were determined based on eight parameters at three different levels. The sources of carbon and nitrogen concentration and their interactions with other precursors were found to be statistically significant factors. When date syrup was used as an additional carbon source, higher BLM amount was obtained in comparison to glucose. It was found that the optimum nitrogen source was achieved with the use of soyabean meal. The combined orthogonal design and response surface methodology predicted optimal conditions for production of BLM to be 138 mg dl-1. A confirmatory experiment of the optimal medium composition produced 142 mg dl-1 in the fifth day fermentation at 30°C. The complex medium containing 40 gml-1 date syrup as additional carbon source enhanced the production of BLM by 73%. The combined statistical approach enabled rapid identification and integration of key medium parameters for optimizing secondary metabolite production and could be very useful in pharma-ceutical screening programs.
Key words: Bleomycin, Streptomyces mobaraensis, orthogonal design, medium optimization, date syrup.
BLM, Bleomycin; SS, soluble starch (millet jelly); GC, glucose;SM, soybean meal; CS, corn steep liquor; DS, date Syrup; Zn, Zinc source (ZnSO4.7H2O); Cu, copper source (CuSO4.5H2O); NO, nitrogen source (NaNO3).
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