通过对大肠杆菌的多维工程,从葡萄糖中有效地生物合成3-基酸
Yufei Zhang1, Junhua Yun2, Guoyan Zhang3
1School of Life Sciences, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou 510006, Guangdong, PR China; School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu, PR China.
Bioresource technology
|October 7, 2023
概括
这项研究对大肠杆菌进行了基因工程,以实现3-基酸 (3-HP) 的可持续生物合成. 结合了代谢和酶工程策略,实现了高位数的3HP生产,克服了以前的局限性.
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:
- 3-基酸 (3-HP) 是一种具有广泛应用的有价值的化学物质.
- 可持续的3-HP生物合成目前的局限性包括缺乏强大的微生物菌株和高发酵成本.
研究的目的:
- 通过菌株工程克服可持续3HP生物合成的局限性.
- 通过优化大肠杆菌中的代谢途径和酶活性来增强3-HP的产生.
主要方法:
- 在大肠杆菌中构建了一个利用葡萄糖的3-HP生物合成途径.
- 采用了传送器工程,代谢动态调制 (Cra-依赖开关) 和酶工程 (YdcW化脱酶).
- 无活性糖醇促进剂 (GlpF) 和利用半理性设计进行酶改进.
主要成果:
- 成功设计了大肠杆菌,从葡萄糖中产生3-HP.
- 克服了中央代谢溢出,并使用替代葡萄糖运输系统和CRA开关缓解了生长迟缓.
- 通过增强的阿尔德海德脱酶活性,消除了有毒的3-基甲基 (3-HPA) 积累.
- 通过料批发发酵,通过0.59mol/mol葡萄糖的产量获得了最终3HP标位52.73g/L.
结论:
- 综合工程策略有效地解决了3HP生物合成的局限性.
- 开发的菌株和发酵过程证明了可持续和具有成本效益的3HP生产的有希望的途径.
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