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在工程化大肠杆菌中增强甲基化白醇的产生及其抗癌活性

Nguyen Quang Huy^1,2, Quyen My Linh¹, Nguyen Thi An Hoa²

¹National Key Laboratory of Enzyme and Protein Technology, University of Science, Vietnam National University, Hanoi (VNU), 334 Nguyen Trai, Thanh Xuan, Hanoi, 10000 Vietnam.

|December 26, 2025

概括

工程微生物成功地产生甲基化白醇,显示出对肺癌和肝癌细胞系的增强抗癌活性. 这种微生物生物合成为植物提取提供了一个可持续的替代品,用于生产有价值的白醇衍生物.

科学领域:

代谢工程是代谢工程.
合成生物学合成生物学
生物技术是生物技术.

背景情况:

植物衍生型 stilbenoid 的resveratrol具有多种生物活性,但其甲基化衍生物提供了更好的稳定性和生物可用性.
目前的白醇类似物生产依赖于低效的植物提取,需要使用微生物生物合成等替代方法.
具有调节基因表达的工程微生物可以增强有价值的向化合物的产生.

研究的目的:

开发一种微生物生物合成途径,用于工程化大肠杆菌 (大肠杆菌) 中的甲基化复星.
为了评估微生物产生的4'-O-甲基复星的抗癌潜力.
优化基因表达和培养条件,以提高产量.

主要方法:

构建合成基因集群,包括O-甲基转移酶 (SaOMT2) 和S-adenosylmethionine (SAM) 合成酶 (EcMetK).
工程化大肠杆菌菌株 (C2) 使用T7促进体和核糖体结合部位 (RBS) 进行个体调节的基因.
优化培养条件 (中等,基质度) 和在5L发酵器中进行发酵.

主要成果:

与控制菌株 (C0) 相比,工程C2菌株的4'-O-甲基复星产量增加了6.1倍.
在5L发酵器中36小时后,生物生产率达到476.72μM (~115.485 mg/L).
4'-O-methylresveratrol对A549 (肺) 和HepG2 (肝) 癌细胞系的细胞毒性作用比resveratrol更强.

结论:

使用工程化大肠杆菌的微生物生物合成是生产4'-O-methylresveratrol的可行和有效方法.
微生物产生的4'-O-甲基复星具有显著的抗癌潜力,需要进一步研究.
这项研究提出了第一份关于微生物合成的4'-O-methylresveratrol抗癌活性的报告.

关键词:

4′-O-甲基复醇的使用.它具有抗癌活性.美国大肠杆菌 (E. coli).甲基转移酶的使用方法复星醇是一种复星.

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