一个合并的伪乌里丁生物制造平台,通过简化设计途径实现
Le Yu1, Ruyi Chen1, Chenyue Zhang2
1Department of Anesthesiology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
Nature communications
|October 6, 2025
概括
这项研究提出了一种可持续且具有成本效益的方法来生产伪尿素 (Ψ),这是mRNA疫苗中的一个关键成分. 这种工程路径使得格拉姆尺度的生产成为可能,解决了生物制造的经济和环境挑战.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 生物化学工程 生物化学工程
背景情况:
- 伪尤里丁 (Ψ) 对mRNA疫苗的有效性和药物开发至关重要.
- 现有的伪乌里丁生产方法面临着经济和环境可持续性的挑战.
研究的目的:
- 开发一个精简和可持续的生物制造平台,用于生产伪尿素 (Ψ).
- 在大肠杆菌中设计一个优化的代谢途径,用于高滴度伪尿素 (Ψ) 合成.
主要方法:
- 设计了一种合成途径,涉及UMP核酶, ΨMP糖酶和 ΨMP酸酶.
- 鉴定并使用UMP偏好的核酶 (NmYgdH) 进行途径构建.
- 优化了大肠杆菌的途径,并采用了依赖于thyA的策略,在5L生物反应器中进行可扩展,环保的生产.
主要成果:
- 使用优化途径在大肠杆菌中达到44.8g·L-1的伪尿素 (Ψ) 标位.
- 在5L生物反应器中证明了45.3g·L-1的可持续生产标位.
- 开发了一种简化的净化策略,其回收率为71%并验证了平台的经济可行性.
结论:
- 工程路径和发酵平台为工业规模的伪尿素 (Ψ) 生物制造提供了可行的蓝图.
- 这项研究提供了一种可持续且具有成本效益的解决方案,用于生产伪尿素 (Ψ) 和相关的核酸分子.
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