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首页> 外文期刊>Biotechnology Progress >Identification of Cellular Objective for Elucidating the Physiological State of Plasmid-Bearing Escherichia coli Using Genome-Scale In Silico Analysis
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Identification of Cellular Objective for Elucidating the Physiological State of Plasmid-Bearing Escherichia coli Using Genome-Scale In Silico Analysis

机译：使用基因组规模的计算机分析确定用于阐明带有质粒的大肠杆菌的生理状态的细胞物镜。

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摘要

The presence of multiple copies of plasmids in Escherichia coli could induce a complex cascade of physiological changes known as the metabolic burden response.In this work,the physiological effect of such plasmid metabolic burden on E.coli metabolism was investigated by constraint-based genome-scale flux modeling.We systematically applied three cellular objectives:(a)maximizing growth rate,(b)maximizing plasmid production,and(c)maximizing maintenance energy expenditure to quantify in silico flux distributions.These simulated results were compared with experimental flux information to identify which of these cellular objectives best describes the physiological and metabolic states of plasmid-bearing(P+)E.coli.Unlike the wild-type E.coli cells that have directed the metabolism toward an optimum growth rate under the nutrient-limited condition,the maximum growth rate objective could not correctly predict the metabolic state of recombinant P+ cells.Instead,flux simulations by maximizing maintenance energy expenditure showed good consistency with experimental observation,indicating that the P+ cells are energetically less efficient and could require higher maintenance energy.This study demonstrates that the cellular objective of maximizing maintenance energy expenditure provides a better description of the underlying physiological state in recombinant microorganisms relevant to biotechno-logical applications.
机译：大肠埃希菌中存在多个拷贝的质粒会诱导一系列复杂的生理变化，称为代谢负荷反应。在这项工作中，通过基于约束的基因组研究了这种质粒代谢负荷对大肠杆菌代谢的生理作用。我们系统地应用了三个细胞目标：（a）最大化生长速率，（b）最大化质粒产量，和（c）最大化维持能量消耗以量化硅通量分布。将这些模拟结果与实验通量信息进行比较确定哪些细胞目标最能描述带有质粒（P +）的大肠杆菌的生理和代谢状态。不同于在营养有限的条件下将新陈代谢导向最佳生长速率的野生型大肠杆菌细胞，最大生长速率目标无法正确预测重组P +细胞的代谢状态。维持能量消耗与实验观察结果具有很好的一致性，表明P +细胞的能量效率较低，可能需要更高的维持能量。这项研究表明，最大化维持能量消耗的细胞目标可以更好地描述重组微生物的潜在生理状态。与生物技术应用有关。

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