Signal peptides for recombinant protein secretion in bacterial expression systems.
Signal peptides for recombinant protein secretion in bacterial expression systems.
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DOI：
10.1186/s12934-018-0901-3
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发表时间：
2018-03-29
影响因子：
6.4
通讯作者：
Freudl R
中科院分区：
文献类型：
--
作者：
Freudl R
将生物技术或药学相关的重组蛋白分泌到细菌表达宿主的培养上清液中极大地促进了它们的下游加工并显著降低了生产成本。在将所需靶蛋白分泌到生长培养基中的过程中的第一步是其穿过细胞质膜的转运。在细菌中，存在两种主要的输出途径，一般分泌或Sec途径和双精氨酸易位或达特途径，用于蛋白质跨质膜的运输。进入这些替代蛋白质输出系统之一的路线需要Sec-或Tat-特异性信号肽与所需靶蛋白的氨基末端融合。由于信号肽除了被各蛋白质易位酶靶向和膜易位所需之外，还对各靶蛋白的生物合成、折叠动力学和稳定性具有额外的影响，因此迄今为止不可能预先预测哪种信号肽在给定的靶蛋白和给定的细菌表达宿主的情况下表现最好。如本文所述，寻找所需蛋白质的最佳信号肽的最有希望的方法是筛选最大可能的信号肽多样性，或者通过使用大型信号肽文库的信号肽变异产生，或者通过使用定点或随机诱变策略优化给定的信号肽产生。
The secretion of biotechnologically or pharmaceutically relevant recombinant proteins into the culture supernatant of a bacterial expression host greatly facilitates their downstream processing and significantly reduces the production costs. The first step during the secretion of a desired target protein into the growth medium is its transport across the cytoplasmic membrane. In bacteria, two major export pathways, the general secretion or Sec pathway and the twin-arginine translocation or Tat pathway, exist for the transport of proteins across the plasma membrane. The routing into one of these alternative protein export systems requires the fusion of a Sec- or Tat-specific signal peptide to the amino-terminal end of the desired target protein. Since signal peptides, besides being required for the targeting to and membrane translocation by the respective protein translocases, also have additional influences on the biosynthesis, the folding kinetics, and the stability of the respective target proteins, it is not possible so far to predict in advance which signal peptide will perform best in the context of a given target protein and a given bacterial expression host. As outlined in this review, the most promising way to find the optimal signal peptide for a desired protein is to screen the largest possible diversity of signal peptides, either generated by signal peptide variation using large signal peptide libraries or, alternatively, by optimization of a given signal peptide using site-directed or random mutagenesis strategies.
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