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基于模型的Escherichia coli的动态工程对于N-乙葡萄糖胺过度生产

Jiangong Lu^1,2, Yaokang Wu^1,2, Chen Deng^1,2

¹Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China.

Biotechnology notes (Amsterdam, Netherlands)

|October 17, 2024

概括

工程细菌通过使用动态调节系统实现了高N-乙葡萄糖胺 (GlcNAc) 生产. 这种代谢工程方法显著提高了Escherichia coli中的GlcNAc产量,用于制药应用.

科学领域:

生物技术是生物技术.
代谢工程是代谢工程.
合成生物学合成生物学

背景情况:

N-乙葡萄糖胺 (GlcNAc) 是一种有价值的葡萄糖胺衍生物,具有越来越多的制药应用.
高效的 GlcNAc 微生物生产对于满足工业需求至关重要.

研究的目的:

为了设计大肠杆菌因过度生产N-乙葡萄糖胺 (GlcNAc).
开发和实施基于模型的动态调节策略,以最大限度地提高 GlcNAc 的产量.

主要方法:

用基因组规模的代谢网络建模和流量平衡分析来确定工程目标.
代谢工程策略包括基因淘汰 (poxB,ldhA,murQ) 和基因增强 (glnA).
组合了CRISPR干扰 (CRISPRi),lacI和pdhR的动态调节系统,用于控制关键的代谢途径.

主要成果:

基因淘汰和增强将GlcNAc标位提高到130.8g/L.
动态抑制pfkA和zwf反应优化了GlcNAc的产生.
在30L生物反应器中,改造的大肠杆菌菌株获得了143.8g/L的最终GlcNAc标位,产量为0.539g/g的葡萄糖.

结论:

一个基于模型的动态调节策略显著提高了E. coli中的GlcNAc产量.
开发的系统为改善微生物合成能力提供了一种系统和潜在的通用方法.

关键词:

动态调节动态调节埃舍里希亚大肠杆菌 (Escherichia coli) 是一个大肠杆菌.代谢工程是代谢工程.N-乙烯基葡萄糖胺是什么?代谢性网络模型.

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