响应面法优化替考拉宁发酵培养基及其扩大培养

Response surface methodology to optimize the fermentation medium of teicoplanin and its expanded culture

目的通过响应面法,优化替考拉宁发酵培养基,并对发酵工艺参数进行优化,来提高其发酵产量。方法以游动放线菌TC19-3p-103为试验菌株,采用单因素试验确定发酵培养基考察因素的参考范围;利用最陡爬坡试验确定响应面试验的中心区域;利用Box-Behnken响应面法,确定了发酵培养基中的有机氮源最佳浓度组合;并对起始搅拌转速与通气量这两个发酵工艺参数进行单因素考察;在发酵过程中,采用流加技术控制碳源浓度。结果经优化的发酵培养基,其摇瓶产量提高了31.6%;50L罐发酵工艺参数优化后,发酵水平达到8558 mg/L。结论优化后的发酵工艺,显著提高了替考拉宁的产量,为其工业化生产奠定了基础。

Objective To optimize the fermentation medium of teicoplanin by response surface methodology and optimize the fermentation process parameters to increase its fermentation yield.Methods The Actinoplanes teichomyceticus TC19-3p-103 was used as the test strain.The single factor test was used to determine the reference range of the fermentation medium to investigate factors.The steepest climbing test was used to determine the central area of the response surface test.The Box-Behnken response surface method was used to determine the optimal concentration combination of organic nitrogen sources in the fermentation medium.The two fermentation process parameters,the initial stirring speed and aeration rate,were investigated by a single factor.The fed-batch technology was used to control the concentration of the carbon source in the fermentation process.Results The optimized fermentation medium increased the shake flask yield by 31.6%.After the optimization of the fermentation process parameters in the 50 L tank,the fermentation level reached 8,558 mg/L.Conclusion The optimized fermentation process has significantly increased the production of teicoplanin and laid the foundation for its industrial production.