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通过一种新的C1转移途径,改善了对大肠杆菌中5-甲基四基酸盐生产的甲基供应

Wen Liu^1,2, Jing Guo^1,3, Wei Lu^1,2

¹CAS Key Laboratory of Bio-Based Materials, Qingdao New Energy Shandong Laboratory, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.

Microbial cell factories

|April 14, 2025

概括

研究人员对大肠杆菌进行了改造,以促进L-5-Methyltetrahydrofolate (5-MTHF) 的产生,这是一种必不可少的活性叶酸形式. 这种微生物生物合成方法实现了创纪录的8.2mg/L标位,为工业应用铺平了道路.

科学领域:

微生物学微生物学
代谢工程是代谢工程.
生物技术是生物技术.

背景情况:

L-5-Methyltetrahydrofolate (5-MTHF) 是叶酸的活性形式,对人类健康至关重要,是必不可少的营养补充剂.
微生物生物合成为5-MTHF生产提供了一个可持续的途径,但目前的产量不足以达到工业规模.

研究的目的:

增强大肠杆菌中5-MTHF的微生物生物合成.
为了克服5-MTHF在工业应用中的产量限制.

主要方法:

通过引入外源C1代谢途径来增加细胞内甲基供应来改造大肠杆菌.
通过过度表达关键基因 (folE,folP,purU) 来优化四基酸盐 (THF) 合成途径.
通过淘汰metE基因,消除了5-MTHF的消耗.

主要成果:

在摇瓶发酵中达到1.075mg/L的5-MTHF标位.
工程菌株M3012在5L生物反应器中产生8.2mg/L的5-MTHF,使用食批发发酵.
这是迄今为止微生物5-MTHF生产报告的最高位数.

结论:

通过新的C1路径和代谢优化,成功设计了大肠杆菌以增强5-MTHF生物合成.
开发的重组菌株显示出显著的产量改善,解决了工业5-MTHF生产的关键瓶.
这项工作为大规模,可持续的5-MTHF生产提供了基础.

关键词:

埃舍里希亚大肠杆菌 (Escherichia coli) 是一个大肠杆菌.5-MTHF是一种5MTHF.代谢工程是代谢工程.甲基供应供应提供甲基.

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