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首页> 外文期刊>Biotechnology Progress >Toward intensifying design of experiments in upstream bioprocess development: An industrial Escherichia coli feasibility study
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Toward intensifying design of experiments in upstream bioprocess development: An industrial Escherichia coli feasibility study

机译：加强上游生物工艺开发实验的设计：工业大肠杆菌的可行性研究

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In this study, step variations in temperature, pH, and carbon substrate feeding rate were performed within five high cell density Escherichia coli fermentations to assess whether intraexperiment step changes, can principally be used to exploit the process operation space in a design of experiment manner. A dynamic process modeling approach was adopted to determine parameter interactions. A bioreactor model was integrated with an artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for heterologous protein production. A model reliability measure was introduced to assess in which process region the model can be expected to predict process states accurately. It was found that the model could accurately predict process states of multiple fermentations performed at fixed conditions within the determined validity domain. The results suggest that intraexperimental variations of process conditions could be used to reduce the number of experiments by a factor, which in limit would be equivalent to the number of intraexperimental variations per experiment. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1343-1352, 2016
机译：在这项研究中，在五个高细胞密度的大肠杆菌发酵中进行了温度，pH和碳底物进料速率的阶跃变化，以评估实验内阶跃变化是否可以主要用于实验设计中，以利用工艺操作空间。采用动态过程建模方法来确定参数交互。将生物反应器模型与人工神经网络集成在一起，该人工神经网络描述了生物量和产物形成速率与异源蛋白质生产的各种补料分批发酵条件的关系。引入了模型可靠性度量，以评估可以期望模型在哪个过程区域中准确预测过程状态。发现该模型可以准确地预测在确定的有效性范围内在固定条件下执行的多次发酵的过程状态。结果表明，工艺条件的实验内变化可用于将实验次数减少一个因子，该极限在一定程度上等于每个实验的实验内变化的数量。 （c）2016美国化学工程师学会生物技术学会。 Prog。，32：1343-1352，2016

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