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An inverse metabolic engineering approach for the design of an improved host platform for over-expression of recombinant proteins in Escherichia coli

机译:一种逆向代谢工程方法用于设计用于在大肠杆菌中过度表达重组蛋白的改良宿主平台

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摘要

BackgroundA useful goal for metabolic engineering would be to generate non-growing but metabolically active quiescent cells which would divert the metabolic fluxes towards product formation rather than growth. However, for products like recombinant proteins, which are intricately coupled to the growth process it is difficult to identify the genes that need to be knocked-out/knocked-in to get this desired phenotype. To circumvent this we adopted an inverse metabolic engineering strategy which would screen for the desired phenotype and thus help in the identification of genetic targets which need to be modified to get overproducers of recombinant protein. Such quiescent cells would obviate the need for high cell density cultures and increase the operational life span of bioprocesses.
机译:背景代谢工程的一个有用目标是产生不生长但具有代谢活性的静态细胞,该细胞将使代谢通量转向产物形成而不是生长。然而,对于像重组蛋白这样的产品,这些产品与生长过程错综复杂地耦合,很难鉴定需要敲除/敲入以获得该所需表型的基因。为了避免这种情况,我们采用了逆向代谢工程策略,该策略将筛选所需的表型,从而帮助鉴定需要进行修饰以获得重组蛋白过量生产者的遗传靶标。这样的静态细胞将消除对高细胞密度培养的需要,并增加生物过程的使用寿命。

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