从氧气反应调节中解脱糖的利用,以在大肠杆菌中高效生产L-乳酸
Meng Wang1,2, Dandan Niu3,4, Mingliang Gao1,2
1State Key Laboratory of Bio-based Fiber Materials, Tianjin University of Science & Technology, Tianjin, 300457, China.
Biotechnology for biofuels and bioproducts
|September 27, 2025
概括
工程化大肠杆菌通过克服代谢限制,有效地从糖糖中产生L-乳酸. 这种生物制造的进步为使用这种丰富的原料的传统方法提供了一个可扩展的,具有成本效益的替代方案.
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:
- 可持续的生物制造需要微生物平台,将低成本原料转化为有价值的化学品.
- 大肠杆菌 (E. coli) 的糖糖发酵受到代谢效率低下的限制,阻碍其用于高价值化学品生产.
- 在无氧条件下,csc操作子的减少表达阻碍了大肠杆菌中糖的代谢.
研究的目的:
- 调查和克服大肠杆菌的代谢瓶,以从糖糖中有效生产L-乳酸.
- 在无氧发酵条件下改造大肠杆菌以提高糖糖的利用率.
- 开发一种可扩展和经济可行的生物制造工艺,使用糖作为碳源.
主要方法:
- 敲除cscR基因和动态转录组概况以分析基因表达变化.
- 无氧活性促进体 (gapA) 的工程,以控制cscA和cscB基因表达.
- 在实验室规模 (5L) 和试点规模 (30L) 生物反应器中优化发酵.
主要成果:
- 重组大肠杆菌菌株090S显示有氧生长增强,但无氧酸产量有限.
- 转录组分析显示,在无氧条件下,csc操作子的显著下调.
- 工程菌株091S在30小时内实现了129.7g/L乳酸 (5L生物反应器) 和145.7g/L (30L生物反应器),比控制增加了3.04倍.
结论:
- 优化促进体驱动的糖糖利用基因 (cscA,cscB) 的过度表达克服了大肠杆菌中的无氧代谢约束.
- 这种工程化大肠杆菌菌株为从糖糖中生产L-乳酸提供了一个可扩展和具有成本效益的平台.
- 这些发现为在工业生物制造中利用富含糖的原料提供了可行的策略.
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