北京大学刘涛研究团队报道了通过基因编码分子转子氨基酸，设计人工荧光蛋白和生物传感器。相关研究成果于2024年11月28日发表在《自然—化学》。

荧光蛋白是生物和医学研究中不可或缺的工具。荧光团通常由初级氨基酸序列编码，在蛋白质折叠时，荧光分子转子结构由此形成。

该文中，受天然荧光团表现出的荧光特性的启发，研究人员设计了一系列具有这种分子转子结构的荧光非规范氨基酸，称为荧光分子转子氨基酸（FMR-AA），类似于天然荧光蛋白荧光团。

通过扩展遗传密码将FMR-AA结合到靶蛋白中，研究人员将它们用作受限蛋白质微环境中的编码荧光团类似物，从而很容易将各种非荧光蛋白转化为人工荧光蛋白。

研究还使用选定蛋白质中的FMR-AA作为灵敏的荧光探针，用于监测蛋白质之间的相互作用，并检测体外和活细胞中的蛋白质构象变化。

这种方法能够产生人工荧光蛋白，并通过微小的修饰从潜在的任何感兴趣的蛋白质中，开发生物传感器。

附：英文原文

Title: Designing artificial fluorescent proteins and biosensors by genetically encoding molecular rotor-based amino acids

Author: Hu, Liming, Cao, Wenbing, Jiang, Yihaofan, Cai, Wenkang, Lou, Xiaoding, Liu, Tao

Issue&Volume: 2024-11-28

Abstract: Fluorescent proteins are indispensable tools in biological and medical research. The fluorophores are typically encoded by the primary amino acid sequence, from which a fluorescent molecular rotor structure forms upon protein folding. Here, inspired by the fluorogenic property exhibited by native fluorophores, we designed a collection of fluorogenic non-canonical amino acids that feature this molecular rotor structure—termed fluorescent molecular rotor amino acids (FMR-AAs)—akin to native fluorescent protein fluorophores. By incorporating FMR-AAs into target proteins through an expanded genetic code, we use them as encoded fluorophore analogues within a confined protein microenvironment, thus readily transforming diverse non-fluorescent proteins into artificial fluorescent proteins. We also use FMR-AAs in selected proteins as sensitive fluorescent probes for monitoring protein–protein interactions and detecting protein conformational changes in vitro and in living cells. This approach enables the generation of artificial fluorescent proteins and the development of biosensors from potentially any protein of interest with minor modifications.

DOI: 10.1038/s41557-024-01675-x

Source: https://www.nature.com/articles/s41557-024-01675-x