在Trichoderma reesei中,有效的细胞外生产胰岛素格拉是由基于分泌的整合性策略所实现的
Aiqin Yan1, Xihai Li1, Di Zhang1
1State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, P. R. China.
Microbial biotechnology
|March 9, 2026
概括
特里科德尔玛可产生胰岛素格拉金,这是治疗糖尿病的重要药物. 这项研究利用融合蛋白和信号来优化其分泌,实现了成功的细胞外生产.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 工业微生物学 工业微生物学
背景情况:
- 胰岛素在糖尿病管理中至关重要,但在传统系统中面临生产挑战.
- 像Trichoderma reesei这样的细丝真菌提供了重组蛋白质分泌的潜力.
研究的目的:
- 确定Trichoderma reesei作为一种可行的宿主,用于分泌胰岛素glargine的产生.
- 为了克服细胞外分泌的局限性并优化产量.
主要方法:
- 工程表达结构具有构成性促进剂和信号.
- 实施了与载体蛋白 (CBH1,CBH2,LA-20) 的融合蛋白策略.
- 优化的信号,包括Aspergillus niger的β-glucoamylase信号.
主要成果:
- 最初的试验显示转录但没有分泌,与内质网膜 (ER) 压力有关.
- 融合蛋白策略,特别是与CBH1的融合蛋白策略,使分泌成为可能,并减少了ER压力.
- 信号的修改导致格拉吉因分泌量增加了四倍,达到58.95mIU/L.
结论:
- 特里科德尔马·里塞 (Trichoderma reesei) 是一个有前途的宿主,可以在细胞外产生胰岛素格拉吉因.
- 开发的策略增强了分泌,并减轻了用于重组蛋白质生产的细胞应激.
- 这种方法支持复杂的治疗性蛋白质的工业规模生产.
关键词:
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