在工程化大肠杆菌中生产L-氨酸的新策略
Mengzhen Nie1,2, Jingyu Wang2, Kechun Zhang3
1Zhejiang University, Hangzhou, 310027, Zhejiang, China.
Microbial cell factories
|July 26, 2023
概括
工程Escherichia coli通过食前体N-乙谷酸盐来有效地产生L-氨酸. 这种新的方法克服了复杂的代谢调节,使得高产量的L-氨酸和酸联合生产成为可能.
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:
- 氨酸是一种重要的氨基酸,具有广泛的工业和制药应用.
- 作为L-氨酸生物合成的前体,N-乙谷氨酸由L-氨酸和乙-CoA合成.
- 大肠杆菌内源性L-氨酸生产面临复杂的代谢调节和产量限制.
研究的目的:
- 开发一种高产量的L-氨酸生产方法,用于工程Escherichia coli.
- 为了克服L-氨酸对N-乙谷氨酸酸合成酶的全性抑制.
- 通过联合生产战略,加强碳来源的利用.
主要方法:
- 删除 argA 基因以阻止内源性 N-乙谷氨酸酸合成.
- 干扰参与L-氨酸代谢和调节的基因 (astA, speF, speB, argR).
- 过度表达L-氨酸生物合成操作子 (argDGI, argCBH) 和用于pyruvate联合生产的工程.
主要成果:
- 工程化大肠杆菌实现了4g/L的L-氨酸产量,产量为0.99mol的L-氨酸/mol的N-乙谷酸盐.
- 联合生产的L-氨酸和酸盐产生了4g/L的L-氨酸和11.3g/L的酸盐.
- 这种新的方法成功绕过了内源代谢调节,用于高产量的L-氨酸合成.
结论:
- 通过在大肠杆菌中使用N-乙谷氨酸食来生产高产的L-氨酸,建立了一个新的战略.
- 该方法有效地规避了L-氨酸对N-乙谷氨酸酸盐合成的监管反.
- 联合生产的L-氨酸和酸证明了碳利用效率的提高.
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