不同补料控制方式发酵生产头孢菌素C的性能比较  

Cephalosporin C fermentation performance under different ammonium sulfate and soybean oil feeding strategies

作　　者：桑美纳[1] 袁国强[2] 李红飞[2] 赵艳丽[2] 倪伟佳[1] 段生兵[1] 刘立明[1] 史仲平[1] 

机构地区：[1]江南大学生物工程学院工业生物技术教育部重点实验室,江苏无锡214122 [2]石药集团河北中润制药有限公司,河北石家庄050041

出　　处：《微生物学通报》2011年第9期1321-1330,共10页Microbiology China

基　　金：国家科技支撑计划项目(No.2007BAI26B02);国家973项目(No.2007CB714303)

摘　　要：在7 L发酵罐下,对利用顶头孢霉菌(Cephalosporins acremonium)发酵生产头孢菌素C(CPC)过程的最优底物流加工艺进行了研究。提出了一种新式硫铵豆油耦联型的硫铵流加策略。该控制策略可将发酵液中的氨态氮浓度控制在3 6 g/L之间,同时满足了发酵前期细胞生长与CPC合成对氮源和硫源的需求,促进了顶头孢霉菌菌丝分化,为发酵后期的CPC高效生产奠定了前期基础。比较了CPC合成期内间歇、匀速和DO-Stat自动流加3种不同豆油流加方式的发酵性能。研究发现,耦联使用硫铵/后程通富氧空气DO-Stat法进行硫铵和豆油的同时补料和CPC发酵,可将碳源浓度与溶解氧浓度DO同时控制于适中水平,使CPC合成以高浓度和低副产物积累的方式进行,最终CPC浓度和得率分别达到35.77 g/L和13.3%。主代谢副产物脱乙酰氧头孢菌素C(DAOC)的积累量和DAOC/CPC分别仅有0.178 g/L和0.5%。Various substrates feeding strategies for cephalosporin C（CPC） efficient production by Cephalosporins acremonium were studied and conducted in a 7 L fermentor.A novel ammonium sulfate feeding strategy in couple with soybean oil addition was proposed.With this strategy,NH4＋ concentration in fermentation broth could be stably maintained in a range of 3-6 g/L throughout fermentation period,simultaneously satisfying the demands on nitrogen and sulfur sources for cells growth and CPC synthesis,promoting Cephalosporins acremonium hyphal split,and creating the prerequisite for the subsequent CPC efficient production.Based on the novel ammonium sulfate feeding strategy,performance of the subsequent CPC fermentations with different soybean oil feeding strategies,namely intermittent,constant rate and automatic DO-Stat feeding was compared.Feeding ammonium sulfate in couple with the soybean oil feeding in a manner of DO-Stat＋oxygen-enriched air aeration at late fermentation phase could control carbon source concentration and DO at adequate levels,ensuring efficient CPC synthesis in a way of high CPC concentration and low by-product accumulation.With this combinational feeding strategy,final CPC concentration and CPC yield could reach 35.77 g/L and 13.3%,respectively,the major by-product,de-acetoxycephalosporin（DAOC） and DAOC/CPC were only 0.178 g/L and 0.5%.

关 键 词：顶头孢霉菌 头孢菌素C DO-Stat 发酵 补料 

分 类 号：TQ465.1[化学工程—制药化工]