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Design and Adaptation of Robust Feeding Profiles for Recombinant E.coli Fed-batch Cultivation Processes*

机译:重组大肠杆菌喂养栽培过程的鲁棒喂养曲线的设计与调整*

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In this paper, the experimental data-based procedure for design and adaptation of robust feeding profiles for recombinant E.coli fed-batch cultivation processes has been proposed. In the first step of the procedure, a maximum glucose consumption rate in biomass growth and target protein production phases must be determined using data from an unlimited growth cultivation. Afterwards, various scenarios for glucose feeding rate need to be designed by setting different levels of glucose consumption rate limitation during the cultivation process. Then the procedure includes the realization of these planned cultivation experiments. The experiments provide the opportunity to select robust and efficient glucose feeding profiles, which then are recommended for implementation in recombinant protein production processes. The proposed procedure also includes a method for adaptation of the designed feeding profile for the case when the process disturbances are significant and glucose begins to accumulate unpredictably in the cultivation medium. The proposed procedure has been tested in simulation studies using the "virtual bioreactor" approach. The simulation tests have shown the efficiency of the proposed procedure. For the realization of the proposed procedure, a required software has been developed and is being prepared for implementation in industrial PLC.
机译:本文提出了一种基于实验数据的设计和适应重组大肠杆菌喂养培养方法的鲁棒喂养曲线的设计和调整的过程。在该方法的第一步中,必须使用来自无限增长培养的数据确定生物质生长和靶蛋白质产生阶段的最大葡萄糖消耗率。然后,通过在培养过程中设定不同水平的葡萄糖消耗率限制,需要设计各种用于葡萄糖喂养速率的情况。然后该程序包括实现这些计划的培养实验。实验提供了选择稳健和有效的葡萄糖进料型材的机会,然后建议在重组蛋白质生产过程中实施。所提出的方法还包括用于改编设计的饲养曲线的方法,因为当过程干扰是显着的并且葡萄糖开始在培养基中不可预测地积累。已经使用“虚拟生物反应器”方法在仿真研究中进行了所提出的程序。仿真试验表明了所提出的程序的效率。为了实现所提出的程序,已经开发了所需的软件,并正在制定工业PLC中的实施。

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