重写多个罕见的编码子可以同时结合多达五种不同的非正规氨基酸
Yu Fang1,2, Wei Yu1,2, Junjie Li1
1Life Sciences Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Nature chemistry
|March 14, 2026
概括
研究人员通过在哺乳动物细胞中实现多种非正规氨基酸 (ncAAs) 的特定位点结合来扩展遗传密码. 这一突破允许复杂的蛋白质工程,并为合成生物学和生物医学开辟了新的途径.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 合成生物学 合成生物学
背景情况:
- 将遗传代码扩展到非正规氨基酸 (ncAAs) 能够进行特定位点的蛋白质修饰.
- 目前在哺乳动物细胞中的方法由于翻译效率低下,仅限于单个ncAA结合.
研究的目的:
- 在哺乳动物细胞中开发一种高效的多类型ncAA整合策略.
- 为了使两个或两个以上不同的ncAAs在特定地点内被纳入蛋白质.
主要方法:
- 开发了一种多种类型的罕见密码子重编码策略.
- 系统地评估和重新定位罕见的编码子.
- 设计了相互直角的氨基-tRNA合成酶/tRNA对.
主要成果:
- 通过在特定位点的两个或三个不同的ncAAs实现蛋白质的表达.
- 在野生类型的蛋白质表达水平上,已证明重编码率高达90%.
- 成功地将多达五种不同的ncAAs纳入一个单一的蛋白质.
结论:
- 开发的战略克服了单一类型的ncAA合并的局限性.
- 能够实现双重生物对角标记和顺序蛋白激活.
- 强调遗传密码对于未来生物医学和合成生物学应用的重新定义性质.
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