在没有对宿主基因组进行修改的情况下,有效地扩展遗传密码
Alan Costello1,2, Alexander A Peterson1,2, David L Lanster1,2,3
1Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Nature biotechnology
|September 11, 2024
概括
这项研究引入了一种新型的编码子压缩策略,用于有效地将非正规氨基酸 (ncAA) 纳入蛋白质. 这种方法增强了遗传密码的扩展,并使得各种新生物分子的创造成为可能.
科学领域:
- 合成生物学 合成生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 现有的将非正规氨基酸 (ncAA) 纳入蛋白质的方法经常面临低效率和上下文依赖的挑战.
- 遗传密码扩展旨在通过结合非自然氨基酸来创建具有新功能的蛋白质.
研究的目的:
- 开发一个更高效和独立于环境的战略,用于使用codon压缩的ncAA整合.
- 为了识别和优化转移RNA (tRNA) -合成酶对扩展遗传密码.
- 建立一个体内生物合成平台,用于创建新宏循环.
主要方法:
- 一种基于等离子体的编码子压缩策略是使用常规的大肠杆菌菌株和本地核糖体开发的.
- 该战略的重点是利用四重码子来提高ncAA整合效率.
- 确定了多个相互直角的tRNA-合成酶对,并优化了它们以结合广泛的ncAAs.
主要成果:
- 开发的编码子压缩策略显著提高了四重编码子的ncAA整合效率,同时最大限度地减少了上下文依赖.
- 确定了12个相互直角的tRNA-合成酶对,并进一步开发了5个用于更广泛的ncAA整合.
- 建立了一个体内生物合成平台,可以创建超过100个新的天然大循环,最多有三个独特的ncAAs.
结论:
- 代码的使用是有效的遗传密码扩展的关键,以前未被识别的因素.
- 开发的战略和资源加速了多重复合遗传密码扩展方面的创新.
- 这项工作有助于发现和生产具有新功能的化学多样化的生物分子.
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