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基因编码的对绿色光敏感的光化素用于对蛋白质功能的顺序控制

Manjia Li¹, Minghao Lu¹, Lijun Wang¹

¹School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen 518055 China tpeng@pku.edu.cn.

Chemical science

|December 1, 2025

概括

研究人员开发了SCouK,一种新型的绿光可激活的非自然氨基酸 (UAA),用于精确控制蛋白质. 这种对可见光敏感的氨酸衍生物能够对活细胞中的蛋白质活性进行序列光控制,从而推进生物研究.

科学领域:

生物化学生化学
分子生物学分子生物学
合成生物学合成生物学

背景情况:

遗传密码的扩展使得非自然氨基酸 (UAA) 的特定部位的结合能够用于蛋白质控制.
现有的光反应性UAA仅限于紫外线/近紫外线,阻碍了同时多蛋白调节.
存在对可见光响应的UAA的需求,以实现正交和顺序蛋白质操纵.

研究的目的:

引入一种新的绿光可激活氨酸衍生物SCouK,用于可见光介导的蛋白质功能的光控制.
为了证明SCouK在细菌和哺乳动物细胞中的特定部位的内置和光激活.
用SCouK.展示多种蛋白质和生物通路的顺序和正交控制.

主要方法:

在蛋白质中编码SCouK的基因编码,SCouK是一种氨酸衍生物,含有可光效的硫氨酸部分.
使用可见光 (绿光,520 nm) 来光激活SCouK,以恢复蛋白质功能 (EGFP,光酶).
展示SCouK在控制激酶活性和cGAS-STING通路中的应用,并使用可激活紫外线光的UAA进行序列激活.

主要成果:

SCouK成功地被遗传编码并被特定地纳入活体细菌和哺乳动物细胞中的蛋白质中.
在30秒内,SCouK通过绿光 (520nm) 证明了高效的光解,恢复了蛋白质功能.
通过SCouK,可以对激酶进行光学控制,对cGAS-STING通路进行时间查询,并首次对两个不同的UAA修饰蛋白进行序列光激活.

结论:

SCouK是第一个可见光响应的氨酸衍生物用于遗传编码,提供精确,非侵入性蛋白质操纵.
它对绿光的响应性,直角激活和高效率使其适合复杂的生物系统.
SCouK对推进功能蛋白研究和治疗应用具有重大潜力.

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