集成的动态控制和酶同定位策略使得高效的stilbenoid生物合成成为可能
Guofu Zhao1, Pengpai Li1, Xinyao Ding1
1MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
Bioresource technology
|February 1, 2026
概括
工程化大肠杆菌通过CRISPRi和酶融合有效地产生像piceatannol和pterostilbene这样的stilbenoid. 这种微生物生物合成提供了一种可持续的替代植物提取和化学合成有价值的自然产品.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 自然产品生物合成 自然产品生物合成
背景情况:
- 斯蒂尔贝诺因是具有重要的生物活性的有价值的植物性多.
- 斯蒂尔化物生产的挑战包括自然丰度低和有毒化学合成路径.
研究的目的:
- 为了设计大肠杆菌以高效生物合成多种stilbenoids.
- 通过代谢工程来克服天然产品制造的局限性.
主要方法:
- 开发了一种对p-酸有反应的CRISPRi系统,用于动态代谢调节.
- 采用了酶共定位策略,包括双酶融合设计.
- 使用直角蛋白质结合系统 (SpyTag/SpyCatcher,SnoopTag/SnoopCatcher) 来进行路径优化.
主要成果:
- 从用L-氨酸补充剂的甘油中获得的piceatannol (583.10 mg/L) 和pterostilbene (1110.92 mg/L) 的最高报告标位.
- 通过优化中间道,显著提高了路径流量.
- 技术经济分析证实了微生物stilbenoid制造的可行性.
结论:
- 综合战略为微生物stilbenoid生物合成提供了一个强大的平台.
- 这种方法为生产高价值天然产品提供了可持续和高效的替代方案.
- 为其他复杂的自然产品的生物合成提供了一个有价值的范式.
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