一个重编程的遗传代码,由32种不同的氨基酸组成
Takayuki Katoh1, Hiroaki Suga1
1Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nucleic acids research
|February 18, 2026
概括
科学家们扩展了基因编码,在20种标准氨基酸之外,结合了11种新的非蛋白质原性氨基酸 (npAAs) 和1种启动性氨基酸 (npAA),并使用人工编码盒分裂来发现药物.
科学领域:
- 合成生物学 合成生物学
- 遗传密码扩展 遗传密码扩展
- 蛋白质工程是一种蛋白质工程.
背景情况:
- 感官密码子的重新分配允许非蛋白质生成氨基酸 (npAAs) 的结合.
- 目前的方法通常将氨基酸构建块的总数限制在20个.
- 以前的人工编码盒分裂显示出希望,但面临效率限制.
研究的目的:
- 为了克服以前的子盒划分方法的局限性.
- 为了扩展基因代码超出标准的20种蛋白质生成氨基酸 (pAAs).
- 为了促进多个npAA的纳入,以产生多样化的类库.
主要方法:
- 应用工程化tRNAs (tRNAPro1E2和tRNAiniP) 到编码盒分裂框架中.
- 优化翻译条件以提高npAA整合效率.
- 用于体外转录的转移RNA (tRNA) 缺乏核酸修饰.
主要成果:
- 成功地将遗传密码扩展到32个氨基酸,包括11个延长型npAAs和1个启动型npAA.
- 保持了所有20个标准PAA的整合.
- 包含具有治疗意义的npAAs,如β-氨基,d-氨基和N-甲基氨基酸,以及宏循环的启动剂.
结论:
- 开发的平台可以扩展遗传密码,以实现多种npAA的结合.
- 这一进步有助于创建用于药物发现的新型宏环库.
- 该平台具有在治疗开发中产生独特化学实体的巨大潜力.
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