从醇到蛋白质:单生物合成和含素的氨酸类似物的遗传编码
Sandhya Jaiswal1, Surendar R Jakka1, Satish Kumar1
1Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, India.
Angewandte Chemie (International ed. in English)
|January 30, 2026
概括
研究人员设计细胞以产生含有的氨基酸,用于蛋白质修饰. 这允许对特定位点的蛋白质进行整合,从而创建具有可调节功能的新型氧化还原活性设计蛋白.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 用非自然氨基酸 (UAA) 扩展遗传密码可以实现新型蛋白质功能,但在UAA合成和细胞传递方面面临挑战.
- 含素的氨基酸为蛋白质工程提供独特的氧化还原和催化性能.
研究的目的:
- 开发一种综合生物合成遗传战略,用于生产和将含有素的UAA,特别是基于的UAA,纳入活细胞中的蛋白质中.
- 使用遗传编码的,设计具有新型氧化还原反应性质的蛋白质.
主要方法:
- 结构导向的工程 氨酸溶酶 (TPL) 在体内酶为UAAs (3-methoxy-, 3-methylthio-和3-methylseleno-L-tyrosine) 的酶性生产.
- 利用进化的直角氨基-tRNA合成酶,将UAA具体结合到绿色光蛋白 (GFP) 中.
- 建立一个单一的体内系统,将UAA生物合成和蛋白质翻译结合起来.
主要成果:
- 通过使用工程化TPL和tRNA合成酶系统,成功地生产并将含的UAA (包括MeSeY) 纳入GFP.
- 通过光检测,光谱学和质谱学确认了UAA的结合.
- 在GFP中通过在Tyr66残留物上安装MeSeY,以及在循环 permuted GFP (cpGFP) 支架中进行可逆回氧切换来证明回氧反应性光.
结论:
- 引入了作为先进蛋白质工程的遗传编码处理器.
- 建立了一个可扩展的战略,整合生物催化和遗传密码扩展,用于创建氧化还原活性设计蛋白.
- 开发了一个系统,减少了UAA生产和纳入的前体需求和细胞毒性.
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