通过细胞毒性缓解和途径优化进行高产量原氨酸IX生物合成的工程大肠杆菌
Peng Sun1, Lin-Lin Qian1, Wen-Liang Xie1
1Laboratory of Biocatalysis and Synthetic Biotechnology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
ACS synthetic biology
|October 27, 2025
概括
研究人员在大肠杆菌中开发了一个合成生物学平台,用于高产量微生物生产原氨酸IX (PP IX). 这克服了细胞毒性和监管问题,使有效的PP IX生物制造成为可能.
科学领域:
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
- 生物技术是生物技术.
背景情况:
- 氨酸和原氨酸IX (PP IX) 一样,在生物系统中是重要的四氧化.
- PP IX是和叶绿素的前体,具有广泛的应用.
- 微生物PP IX生产在细胞毒性和生物合成调节方面面临挑战.
研究的目的:
- 为高效和可扩展的PP IX微生物生产设计一个大肠杆菌平台.
- 为了克服PP IX生物合成中细胞毒性和内源性调节控制的局限性.
- 通过空间时空路径治理建立一种新的模式来产生细胞毒性代谢物.
主要方法:
- 在大肠杆菌中实施合成生物学策略,以优化途径.
- 引入了一种过度活跃的5-aminolevulinic acid合成酶,并使用基于sRNA的敲击来重新平衡分支路径.
- 集成了MacAB-TolC流出系统,以减轻细胞内PP IX积累.
主要成果:
- 在5L生物反应器中实现了前所未有的PP IX标位3.90 g/L和65.0 mg/L/h的生产率.
- 通过排泄系统减少了16%的细胞内PP IX积累.
- 通过通过动态路径修改共同生产0.24g/L血来证明代谢可塑性.
结论:
- 建立了一个有效的合成生物学平台,用于微生物PP IX的生产,克服毒性和监管障碍.
- 工程化的大肠杆菌底盘为下一代氨酸生物制造提供了一个多功能平台.
- 通过空间时空路径控制开发了一种新的细胞毒性代谢物合成方法,绕过传统的权衡.
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