在益生菌底盘中产生的具有整合素结合基因的氧化原蛋白样结构:合成,结构稳定性和体外生物活性
Zheng Zhang1, Jing Zhang2, Lihui Zheng2
1School of Life Science, East China Normal University, Shanghai 200241, China; Department of Biomedical Engineering, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China.
Colloids and surfaces. B, Biointerfaces
|December 13, 2025
概括
工程细菌生产氧化原蛋白,生物医学用途的关键蛋白质. 这种改进的原体显示出更好的稳定性和减少的免疫反应,克服了常见的生产挑战.
科学领域:
- 生物技术是生物技术.
- 生物材料科学 生物材料科学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 大肠杆菌中的重组原蛋白生产面临着诸如内毒素污染和不良的prolyl氧化等挑战.
- 这些局限性阻碍了原在生物医学应用中的使用.
研究的目的:
- 为了设计一种细菌底盘,以生产具有改进性质的氧化原蛋白.
- 为了克服内毒素污染和增强氧化,以改善原蛋白功能.
主要方法:
- 经过工程设计的E. coli Nissle 1917 (EcN) 将与Bacillus anthracis prolyl 4-hydroxylase (BaP4H) 共同表达一种人类的III型原蛋白样蛋白 (R8).
- 使用LC-MS/MS量化原蛋白产量和氧化率.
- 评估了产生的原蛋白的热稳定性,自我组装,免疫性和生物相容性.
主要成果:
- 实现了0.26 mg/mL的氧化原蛋白的产量,氧化率为60%.
- 在65个残留物中的33个中确认了proline修饰.
- 证明了增强的热稳定性,三环螺旋完整性和纤维状网络形成.
- 与传统大肠杆菌的原体相比,显示免疫性降低.
- 呈现出极好的生物相容性,促进纤维细胞的增殖和迁移.
结论:
- 使用工程 EcN 开发了一种生产生物活性,化原蛋白的策略.
- 强调了化在增强原体稳定性,降低免疫性和改善生物相容性方面发挥的关键作用.
- 建立了一个有前途的平台,用于产生高质量的原蛋白,用于生物医学应用.
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