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重组毕氏酵母结构模型的改进及实验验证

Modification and Validation of the Structured Model for P.pastoris

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【作者】 任海涛袁景淇邓建慧贺秉坤

【Author】 REN Hai-tao~1,YUAN Jing-qi~(1,2),DENG Jian-hui~3,HE Bing-kun~3 (1. Dept. of Automation, Shanghai Jiaotong Univ., Shanghai 200030, China; 3. North China Pharmaceutical Corporation, Shijiazhuang 050015)

【机构】 上海交通大学自动化系华北制药集团新药中心华北制药集团新药中心 上海200030上海200030华东理工大学生物反应器工程国家重点实验室上海200237石家庄050015石家庄050015

【摘要】 对早先建立的甲醇营养型重组毕氏醇母(Pichiapastoris)结构模型的产物生成部分进行了动态改进.甲醇流加初期蛋白生成所需的酶系尚处于诱导期,为了描述该酶系浓度和活性从低到高对产物比生成速率的影响,引入了一阶闭环调节器模型加以逼近,同时考虑了细胞体积增大对胞内酶系浓度的稀释作用.设计了6次实验以验证模型的有效性.结果表明,该模型能对细胞生长和蛋白生成给出满意的描述,同时,各罐批间参数变化不是很大,表明该模型具有较强的鲁棒性.

【Abstract】 The structured model proposed earlier for the recombinant Pichia pastoris was improved in the transients of product formation. At the beginning of the methanol growth phase, a first-order closed-loop regulator was introduced to describe the induction of the enzyme pool responsible for product formation. In this regulator model, the dilution effect resulted from cell growth on the enzyme pool was taken into account. Six cultivations were carried out for the purpose of model validation. The testing results indicate that the biomass and protein concentration can be well described by the improved model. In addition, relatively small deviation of the identified parameters among different experiments indicates the robustness of the model.

【基金】 国家自然科学基金项目(60174024);国家高技术研究发展计划(863)资助项目(2001AA413110)
  • 【文献出处】 上海交通大学学报 ,Journal of Shanghai Jiaotong University , 编辑部邮箱 ,2004年04期
  • 【分类号】Q933-33
  • 【被引频次】5
  • 【下载频次】114
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