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一个可光激活的内核酶的AlphaFold3引导优化,用于自上而下的基因组工程

Hideyuki Yone¹, Hiromitsu Kono¹, Moritoshi Sato²

¹Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.

The Journal of biological chemistry

|September 26, 2025

概括

人工智能驱动的蛋白质设计增强了用于基因组工程的光激活酶. 阿尔法Fold3建模指导了改进,导致了具有改变DNA相互作用和酵母菌中基因组重组增加的新变体.

科学领域:

生物技术是生物技术.
合成生物学合成生物学
结构生物学结构生物学

背景情况:

人工智能,特别是蛋白质结构预测,正在彻底改变酶工程.
可光激活的限制酶提供了对基因组工程的精确控制.
MagMboI是一种分裂酶,利用光感应二分化来控制核酶活性.

研究的目的:

通过人工智能引导的结构洞察来增强MagMboI可光激活的限制酶.
研究MagMboI-DNA相互作用的结构基础,以改进酶设计.
开发先进的光控制基因组工程工具.

主要方法:

使用AlphaFold3来建模MagMboI-DNA复杂结构.
采用了与光感应二元化模块的分裂蛋白策略.
在Saccharomyces cerevisiae中引入并测试了一种重新设计的酶变体 (MagMboI-plus).

主要成果:

AlphaFold3提供了对MagMboI与其5'-GATC-3'DNA点相互作用的结构见解.
确定了一个替代的分裂地点,增加了MagMboI-plus.com的接口面积和复杂稳定性.
MagMboI-plus在体内显示了DNA裂变活动的增加,但在光激活时也显示了更多的基因组重组.

结论:

基于AI的结构预测加速了工程酶的功能改进.
AlphaFold3促进了新型基因组工程工具的合理设计.
重新设计的MagMboI-plus变种展示了光控制基因组编辑应用的潜力,并突出了对光控制基因组编辑应用的考虑.

关键词:

阿尔法Fold3是什么意思造成的DNA损伤是DNA损伤.修复DNA的修复DNA的修复人工智能的人工智能是人工智能.结核酶 (endonuclease) 的作用是什么基因组的重新排列是基因组的重新排列.视觉遗传学视觉遗传学蛋白质工程工程蛋白质工程蛋白质结构蛋白质结构限制酶的限制酶是什么

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