生物传感器辅助的多目标基因微调,用于Escherichia coli中N-乙神经胺酸的生产,其中唯一的碳来源是葡萄糖
Bin Qi1,2,3,4, Jianing Zhang1,2,3,4, Wenlong Ma5
1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Journal of agricultural and food chemistry
|April 10, 2025
概括
工程Escherichia coli有效地从葡萄糖中产生N-乙神经胺酸 (NeuAc). 这项研究优化了代谢途径和关键基因,实现了工业应用的创纪录的NeuAc标位和生产率.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 微生物发酵 微生物发酵
背景情况:
- N-乙神经胺酸 (NeuAc) 在食品和医药中至关重要.
- 目前的微生物生产面临着高成本和低效率等挑战.
- 优化葡萄糖利用是经济高效的NeuAc生物合成的关键.
研究的目的:
- 用葡萄糖设计大肠杆菌以提高NeuAc的产生.使用葡萄糖.
- 为了识别和优化关键的基因和路径,用于NeuAc生物合成.
- 开发一种生物传感器,用于高通量查和菌株改善.
主要方法:
- 通过优化葡萄糖利用,竞争性途径和氧化还原平衡来改造大肠杆菌.
- 系统上调通路基因以确定关键目标.
- 开发了一个NeuAc-响应的生物传感器,并使用流细胞计来进行高通量查.
- 三个关键基因的协同优化表达 (glmS-glmM-SeglmU集群).
主要成果:
- 确定了glmS-glmM-SeglmU基因集群作为一个关键的目标.
- 开发了一种NeuAc生物传感器,其响应率为10.62倍.
- 在3L生物反应器中实现了58.26g·L−1的NeuAc标位,生产率为0.83g·L−1·h−1.
- 获得了一种高效的NeuAc生产菌株 (A39).
结论:
- 成功设计了大肠杆菌以从葡萄糖中产生高水平的NeuAc.
- 证明了生物传感器辅助代谢工程对菌株优化的有效性.
- 实现了创纪录的NeuAc生产,为工业应用铺平了道路.
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