Research work was carried out to describe the kinetics of cell growth, substrate consumption and product formation in batch fermentation of rapamycin using shake flask as well as laboratory-scale fermentor. Fructose was used as the sole carbon source in the fermentation media. Optimization of fermentation parameters and reliable mathematical models were used for the maximum production of rapamycin from Streptomyces hygroscopicus MTCC 4003. The experimental data for microbial production of rapamycin fitted well with the proposed mathematical models. Kinetic parameters were evaluated using best fit unstructured models, viz. Andrew's model, Monod model, Yano model, Aiba model. Andrew's model showed a comparatively better R2 value (0.9849) among all tested models. The values of maximum specific growth rate (μmax), saturation constant (KS), inhibition constant (Ki), and growth yield coefficient (YX/S) were found to be 0.008 (h-1), 2.835 (g/L), 0.0738 (g/L), and 0.1708 (g g-1), respectively. The optimum production of rapamycin was obtained at 300 rpm agitation and 1 vvm aeration rate in the fermentor. The final production of rapamycin in shake flask was 539 mg/L. Rapamycin titer found in bioreactor was 1,316 mg/L which is 52 % higher than the latest maximum value reported in the literature.
Keywords: Antibiotic; Growth kinetics; Rapamycin; Streptomyces hygroscopicus; Substrate inhibition.