对C-H氧化不特定的过氧酶进行计算理性设计
Ruichen Gao1, Xiaodi Fu2, Zonglin Li3
1Lab of Applied Biocatalysis, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, School of Food Science and Engineering, South China University of Technology, Guangdong 510006, China.
Science advances
|January 30, 2026
概括
计算理性设计增强了非特异性过氧酶 (UPO) 用于碳氧化. 工程UPO变种显示13倍更高的活性和>99%的酶选择性,克服了合成化学的局限性.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 合成化学 合成化学
- 计算生物学是一种计算生物学.
背景情况:
- 非特异性过氧酶 (UPO) 通过过氧化催化直接的碳- (C-H) 氧化.
- 对于合成化学来说,UPO是有价值的,但往往由于活性较低和选择性较差而受到影响.
- 工程UPO对于扩大其在C-H氧化反应中的应用至关重要.
研究的目的:
- 采用计算理性设计来提高UPO的催化性能.
- 为了确定能改善UPO活性和enantioselectivity的特定突变.
- 了解增强UPO功能的结构基础.
主要方法:
- 使用计算理性设计系统地导航酶序列空间.
- 在子选和有益突变的预测.
- 酶变体的表征,以评估活性和酶选择性.
主要成果:
- 鉴定了UPO变体,其催化活性增加了13倍.
- 在氧化反应中达到>99%的反抗选择性.
- 确定了165位的lysine (lys165) 作为一个关键的残留物,影响了活性和酶选择性.
结论:
- 计算理性设计有效地克服了酶工程的进化约束.
- 工程UPO提供高效和选择性的生物催化剂,以挑战C-H氧化反应.
- 这种方法为开发针对合成化学应用的定制酶提供了一条途径.
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