定向进化促进UGT85A1糖化,以提高甲基糖化物生产
He Ma1, Huayi Liu1, Qingjie Xiao2
1Frontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin 300072, China.
Journal of agricultural and food chemistry
|January 22, 2026
概括
我们设计了一种植物酶,以促进微生物生产有价值的糖化物,如化. 这一突破增强了可持续的食品和制药成分制造.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 酶工程是什么? 酶工程是什么?
背景情况:
- 糖化物是重要的植物化合物,具有重要的食品和制药潜力.
- 低自然丰富的糖化物如沙利德化物阻碍了大规模生产.
- 微生物生物合成提供了一个可持续的替代方案,它取决于高效的甘氨基转移酶.
研究的目的:
- 设计一种高效的葡萄糖转移酶,以增强微生物的类葡萄糖的产生.
- 开发一个强大的平台,用于高价值植物代谢物的生物合成.
主要方法:
- 代和突变发生法 (ISM) 用于设计UGT85A1酶.
- 鉴定并描述了高活性突变DHG (G114D/F217H/C128G).
- 用分子动力学模拟来分析增强酶活性的结构基础.
- 在酵母菌株中表达了DHG,这些酵母菌株是为生产醇和氧醇而设计的.
主要成果:
- 与野生型UGT85A1.1.相比,工程突变DHG的催化效率增加了23.6倍.
- 分子动力学揭示了DHG中稳定的基质结合和优化的催化几何.
- 在工程酵母中,DHG使得2.70g/L的沙利德化物和1.63g/L的氧沙利德化物的产生成为可能.
- 这些标位代表了Saccharomyces cerevisiae中这些化合物在摇瓶条件下报告的最高标位.
结论:
- 工程植物甘氨基转移酶,如UGT85A1,可以显著提高微生物甘氨基酸的生产.
- 突变的DHG提供了一个高效的生物催化剂,用于salidroside和hydroxysalidroside生物合成.
- 这项研究通过酵母代谢工程建立了一个可扩展的平台,用于通过酵母代谢工程可持续生产有价值的糖化物.
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