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代谢修改中央和竞争性代谢途径,以增强D-潘托酸合成
Hai-Yan Zhou1,2, Yi-Hong Chen1,2, Dou-Dou Chen1,2
1National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
通过工程代谢途径,在大肠杆菌中增强了维生素B5前体D-潘托酸的微生物合成. 这显著增加了D-潘托酸的产量,并减少了副产品.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 微生物生物技术 微生物生物技术
背景情况:
- D-潘托酸是维生素B5合成的关键前体.
- 目前用于D-潘托酸的微生物生产方法的产量很低.
- 大肠杆菌是微生物生物合成的常见宿主.
研究的目的:
- 改善大肠杆菌中D-潘托酸的微生物生物合成.
- 通过设计中心代谢和副产品形成途径来提高D-潘托酸产量.
- 为了减少α-谷氨酸 (α-KG) 和其相关副产品的积累.
主要方法:
- 在大肠杆菌中中央代谢途径的工程.
- 使用CRISPRi系统对参与α-KG代谢和运输的基因进行基因操纵.
- 在摇瓶和生物反应器中优化D-潘托酸的生产.
主要成果:
- 最初的工程增加了D-潘托酸标位从0.75g/L增加到1.55g/L.
- 对α-KG相关途径的有针对性的修改进一步改善了D-潘托酸生物合成.
- 在摇瓶中达到2.03g/L,在5L生物反应器中达到14.78g/L,副产品减少.
结论:
- 针对α-KG积累的代谢工程有效地增强了Escherichia coli中的D-潘托酸生物合成.
- 这项研究提出了一种改善D-潘托酸生产的新策略.
- 这些发现提供了有关代谢物生物合成的代谢调节的见解.
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