营养条件和温度对利福霉素B生产强度的影响  

Effect of nutritional conditions and temperature on the production intensity of rifamycin B

作　　者：孙新强 陈克杰 杨一恭 王红伟 陈迎迎[2] 周旭燕[2] 邵东[2] 徐作武[2] SUN Xinqiang;CHEN Kejie;YANG Yigong;WANG Hongwei;CHEN Yingying;ZHOU Xuyan;SHAO Dong;XU Zuowu(Zhejiang Changhai Pharmaceutical Co.,Ltd.,Shaoxing 312366,China;Zhejiang Medicine Co.,Ltd.,Xinchang Pharmaceutical Factory,Shaoxing 312500,China)

机构地区：[1]浙江昌海制药有限公司,浙江绍兴312366 [2]浙江医药股份有限公司新昌制药厂,浙江绍兴312500

出　　处：《发酵科技通讯》2020年第2期63-67,共5页Bulletin of Fermentation Science and Technology

摘　　要：为提高利福霉素B产量和生产强度,在补料摇床上考察了发酵培养基初始葡萄糖质量浓度、无机氮源组合和基质质量比的影响,并在70 L发酵罐上进行变温培养提高溶氧,最后在10 m3发酵罐上进行稳定性验证。结果表明:补料摇床上最适初始葡萄糖质量浓度为80 g/L,无机氮源质量浓度组合为6 g/L KNO3和3 g/L (NH4)2SO4,最适基质质量比为对照组的115%。将获得的配方优化工艺进行变温培养,可提高92~155 h溶氧水平。在10 m3发酵罐上进行5批次中试稳定性验证,利福霉素B效价为(25 647.6±326.6)μg/mL,较优化前提高了16.6%。To further improve the titer and productivity of rifamycin B by Amycolatopsis mediterranei XC-301,the effects of initial glucose mass concentration of the fermentation medium,the combination of inorganic nitrogen source and substrate concentration were investigated in feeding shaker.Moreover,a temperature-variable cultivation strategy was further adopted to improve the dissolved oxygen level in the low oxygen period in a 70 L fermenter.The stability of the established process was further verified in 10 m 3 fermenter.The results showed that the optimal initial glucose concentration was 80 g/L,the optimal combination of inorganic nitrogen sources was 6 g/L KNO 3 and 3 g/L(NH 4)2SO 4 and the optimal substrate concentration was 115%.When the temperature-variable cultivation strategy was applied to the optimized fermentation medium,the dissolved oxygen level was increased between 92 and 155 h of the fermentation.The stability of 5 batches of pilot tests on the 10 m 3 fermenter was tested.The titer of rifamycin B reached(25647.6±326.6)μg/mL,which was 16.6%higher than that of the original process.

关 键 词：利福霉素B 发酵优化 变温培养 地中海拟无枝酸菌 

分 类 号：TQ465.9[化学工程—制药化工]