The Problem of Expression of Multidisulfide Bonded Recombinant Proteins in E. coli
The Problem of Expression of Multidisulfide Bonded Recombinant Proteins in E. coli
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DOI：
10.1007/978-1-4419-7273-6_9
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发表时间：
2011-01-01
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影响因子：
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通讯作者：
Georgiou, George
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文献类型：
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作者：
Arredondo, Silvia A.;Georgiou, George
重组蛋白目前在制药工业中发挥着重要作用。通常，具有治疗价值的蛋白质含有复杂的二硫键模式，这是折叠、稳定性和/或功能所必需的。尽管在大肠杆菌中折叠具有多个二硫键的蛋白质带来了相当大的挑战，但近年来开发的一些方法现在可以用于大量生产此类蛋白质。在这里，我们总结了大肠杆菌中二硫键的形成和主要策略，旨在优化多二硫重组蛋白的表达，通过分泌到胞质周围空间，在细胞质中表达，使其有利于在胞质周围形成二硫键，最后在细胞外合成。
Recombinant proteins currently play an important role in the pharmaceutical industry. Very frequently, proteins of therapeutic value contain complex disulfide bond patterns that are necessary for folding, stability, and/or function. Although the folding of proteins with multiple disulfide bonds in E. coli poses considerable challenges, a number of approaches developed in recent years can now be deployed for the production of such proteins at significant yields. Here, we present a summary of disulfide bond formation in E. coli and the main strategies aimed toward optimization of multidisulfided recombinant protein expression by secretion into the periplasmic space, expression in the cytoplasm of strains engineered to favor the formation of disulfide bonds in that compartment, and finally cell-free synthesis.