Study On Fermentation Process Of Josamycin

Josamycin is a kind of 16-macrolide antibiotics produced by Streptomyces narbonensis var. Josamyceticus. It is not easy to induce resistance and it cure diseases that are caused by gram-positive and gram-negative bacterium. It is important to increase the titre of Josamcyin.We optimized the componets of the medium and the condition of culture, observed the adding time and quantity of precursors effects on the titre of josamycin. We testd carbon source, nitrogen source, orthogonal design experiment, steepest ascent expriment and central compose expriment on the fermentation of josamycin. The optimum medium was: glucose was 1.51%, corn starch was 4%, fish meal was 2%, gluten powder was 2%, bean oil was 0.5%, MgSO₄ was 0.06%, K₂HPO₄ was 0.15%, CaCO₃ was 0.3%, NaCl was 0.1%. Under the conditon of optimized fermentation medium, the titre of josamycin could reach 576μg/mL. It increasd 78.9% than the ratio optimization. In the processes of optimizing culture condition, impact of temperature, table rotational speed, primary pH, flask column, innoculation time and innoculation content on fermentation had been studied. The result showed that the optimum temperature was 28℃, table rotational speed was 180r/min, primary pH was 7.5, flask column was 25mL/150mL, innoculation time was 36h, innoculation content was 8%. Propanol could increase titre. By using the optimization medium and condition, added n-propanol 0.4% to fermentor when the fermentation time comes to 0h. The titre of josamycin was 625μg/mL.Based on the results in shake flasks, josamycin fermentation was scaled up in a 16L fermentor. The metabolic characteristic of Streptomyces narbonensis var. Josamyceticus in the 16L fermentor included pH, sugar metablization, biomass and titre. We used the fed-batch fermentation with intermitted culture. To keep sugar concentration on 10g/L, we made up sugar every 12h. Fermentation period was 168h. The titre of josamycin in Fermentation pot was 518μg/mL.