研究人员开发了一种罕见密码子重编码策略，利用TCG密码子的相对稀有性，通过系统工程和大数据模型预测，实现了高选择性和高效的非经典氨基酸（ncAA）融合。
研究人员强调了这一策略的广泛实用性，它可以在野生型蛋白表达水平上将数十个ncAA加入到各种功能蛋白中，也可以在哺乳动物细胞中合成具有多达六个位点ncAA或四个不同ncAA的蛋白，并将其用于下游应用。
据介绍，对ncAA进行基因编码的能力使蛋白质具有更好或以前未知的特性。然而，哺乳动物细胞中的现有策略依赖于引入空白密码子来整合ncAA，其效率低下，限制了其广泛应用。
附：英文原文
Title: Rare codon recoding for efficient noncanonical amino acid incorporation in mammalian cells
Author: Wenlong Ding, Wei Yu, Yulin Chen, Lihui Lao, Yu Fang, Chengzhu Fang, Hongxia Zhao, Bo Yang, Shixian Lin
Issue&Volume: 2024-06-07
Abstract: The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, we developed a rare codon recoding strategy that takes advantage of the relative rarity of the TCG codon to achieve highly selective and efficient ncAA incorporation through systematic engineering and big data–model predictions. We highlight the broad utility of this strategy for the incorporation of dozens of ncAAs into various functional proteins at the wild-type protein expression levels, as well as the synthesis of proteins with up to six-site ncAAs or four distinct ncAAs in mammalian cells for downstream applications.
DOI: adm8143
Source: https://www.science.org/doi/10.1126/science.adm8143