Research Network ŁUKASIEWICZ - Institute of Biotechnology and Antibiotics, Staroscinska 5, 02-516, Warsaw, Poland.
Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, S10 2TN, Sheffield, UK.
Mol Biotechnol. 2019 Oct;61(10):763-773. doi: 10.1007/s12033-019-00201-6.
Escherichia coli is one of the most widely used hosts for the production of heterologous proteins. Within this host, the choice of cloning vector constitutes a key factor for a satisfactory amplified expression of a target gene. We aimed to develop novel, unpatented expression vectors that enable the stable maintenance and efficient overproduction of proteins in E. coli. A series of expression vectors based on the ColE1-like pIGDM1 plasmid were constructed. The vectors named pIGDMCT7RS, pIGDM4RS and pIGDMKAN carry various antibiotic resistance genes: chloramphenicol, ampicillin or kanamycin, respectively. Two derivatives contain the inducible T7 promoter while the third one bears the constitutive pms promoter from a clinical strain of Klebsiella pneumoniae. The pIGDM1-derivatives are compatible with other ColE1-like plasmids commonly used in molecular cloning. The pIGDMCT7RS and pIGDM4RS vectors contain genes encoding AGA and AGG tRNAs, which supplement the shortage of these tRNAs, increasing the efficiency of synthesis of heterologous proteins. In conclusion, pIGDMCT7RS, pIGDM4RS and pIGDMKAN vectors, with significantly improved features, including compatibility with vast majority of other plasmids, were designed and constructed. They enable a high-level expression of a desired recombinant gene and therefore constitute a potential, valuable tool for pharmaceutical companies and research laboratories for their own research or for the production of recombinant biopharmaceuticals.
大肠杆菌是生产异源蛋白最广泛使用的宿主之一。在该宿主中,克隆载体的选择是目标基因得到满意扩增表达的关键因素。我们旨在开发新型的、非专利的表达载体,以实现蛋白质在大肠杆菌中的稳定维持和高效生产。构建了一系列基于 ColE1 样 pIGDM1 质粒的表达载体。这些载体分别命名为 pIGDMCT7RS、pIGDM4RS 和 pIGDMKAN,分别携带氯霉素、氨苄青霉素或卡那霉素等不同的抗生素抗性基因。其中两个衍生物含有可诱导的 T7 启动子,而第三个则带有来自临床肺炎克雷伯菌的组成型 pms 启动子。pIGDM1 衍生物与分子克隆中常用的其他 ColE1 样质粒兼容。pIGDMCT7RS 和 pIGDM4RS 载体包含编码 AGA 和 AGG tRNA 的基因,这补充了这些 tRNA 的短缺,提高了异源蛋白的合成效率。总之,设计并构建了具有显著改进特征的 pIGDMCT7RS、pIGDM4RS 和 pIGDMKAN 载体,包括与绝大多数其他质粒的兼容性。它们能够实现所需重组基因的高水平表达,因此对于制药公司和研究实验室来说,它们是一种有潜力的、有价值的工具,可用于自身研究或生产重组生物制药。