在大肠杆菌中通过糖转移酶进化和代谢途径优化进行 Baicalein-7-O-xyloside 的工程有效生物合成
Xiaomeng Zhang1, Zhipeng Qi2, Guosheng Xiao1
1College of Biology and Food Engineering, Chongqing Three Gorges University, Wanzhou, Chongqing 404199, China.
Journal of agricultural and food chemistry
|November 4, 2025
概括
通过使用一种新型的甘氨基转移酶和代谢途径优化工程化贝卡莱因酸生产. 这种方法显著提高了这种生物活性化合物的产量,用于潜在的治疗应用.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 自然产品化学 自然产品化学
背景情况:
- 拜卡莱因是*Scutellaria baicalensis*的天然产品,具有较差的可溶性和生物利用性.
- 糖化是扩大天然产品多样性和改善其特性的一个关键过程.
研究的目的:
- 通过使用*Arabidopsis thaliana* glycosyltransferase AtUGT73B1.1. 来设计一种新的贝卡莱因化物.
- 通过酶修饰和代谢工程来提高贝卡林化物的生产产量和选择性.
主要方法:
- 使用AtUGT73B1进行工程化百甲烯基化物,并进行局部定向突变发生 (G157S) 来改变基质特异性.
- 研究了通过淘汰基因 (*ushA*, *pgi*, *zwf*) 和引入细胞质解路径 (CPP) 的细胞内糖供体调节.
- 优化了工程菌株*B73uc*的代谢途径和发酵条件.
主要成果:
- G157S突变增强了UDP-糖活性,削弱了UDP-葡萄糖活性,提高了Baicalein xyloside生产的选择性.
- 对糖捐赠者的淘汰策略是无效的,但引入CPP显著提高了Baicalein xyloside的产量.
- 改造品种*B73uc*的高标位为198.4±3.9mg/L的贝卡莱因化物.
结论:
- 结合酶和代谢工程提供了一个高效和有选择的路径,用于Baicalein xyloside的生产.
- 代谢工程策略,特别是CPP,对于增强甘氨酸生物合成至关重要.
- 这项研究使生物活性糖化物具有改善的物理化学性质的可扩展生产成为可能.
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