Institute of Microbial Technology, Chandigarh, India.
PLoS One. 2014 Jul 7;9(7):e101201. doi: 10.1371/journal.pone.0101201. eCollection 2014.
Because of a large number of molecular similarities with higher eukaryotes, the fission yeast Schizosaccharomyces pombe has been considered a potentially ideal host for expressing human proteins having therapeutic and pharmaceutical applications. However, efforts in this direction are hampered by lack of a strong promoter. Here, we report the isolation and characterization of a strong, constitutive promoter from S. pombe. A new expression vector was constructed by cloning the putative promoter region of the lsd90 gene (earlier reported to be strongly induced by heat stress) into a previously reported high copy number vector pJH5, which contained an ARS element corresponding to the mat2P flanking region and a truncated URA3m selectable marker. The resulting vector was used to study and compare the level of expression of the luciferase reporter with that achieved with the known vectors containing regulatable promoter nmt1 and the strong constitutive promoter adh1 in S. pombe and the methanol-inducible AOX1 promoter in Pichia pastoris. Following growth in standard media the new vector containing the putative lsd90 promoter provided constitutive expression of luciferase, at a level, which was 19-, 39- and 10-fold higher than that achieved with nmt1, adh1 and AOX1 promoters, respectively. These results indicate a great potential of the new lsd90 promoter-based vector for commercial scale expression of therapeutic proteins in S. pombe.
由于与高等真核生物有大量的分子相似性,裂殖酵母 Schizosaccharomyces pombe 被认为是表达具有治疗和药物应用的人类蛋白质的潜在理想宿主。然而,由于缺乏强启动子,在这方面的努力受到了阻碍。在这里,我们报告了一种来自 S. pombe 的强组成型启动子的分离和特性。通过将先前报道的受热应激强烈诱导的 lsd90 基因的假定启动子区域克隆到先前报道的高拷贝数载体 pJH5 中,构建了一个新的表达载体,该载体包含与 mat2P 侧翼区域对应的 ARS 元件和截短的 URA3m 选择性标记。使用所得载体研究并比较了荧光素酶报告基因的表达水平,与已知的含有可调节启动子 nmt1 和强组成型启动子 adh1 的载体在 S. pombe 中的表达水平以及甲醇诱导的 AOX1 启动子在毕赤酵母中的表达水平进行了比较。在标准培养基中生长后,含有假定 lsd90 启动子的新载体提供了荧光素酶的组成型表达,其水平分别比 nmt1、adh1 和 AOX1 启动子高 19 倍、39 倍和 10 倍。这些结果表明,基于新的 lsd90 启动子的载体在 S. pombe 中用于商业规模表达治疗性蛋白质具有很大的潜力。