《生命科学》 2024, 36(5): 593-606
化学合成生物学的研究进展
摘 要：
化学合成生物学作为化学与合成生物学交叉融合的产物，对遗传密码、新型生化途径的工程化拓展具有重要意义。它通过创造自然界中不存在的或改造现有的生物系统，合成非天然核酸、氨基酸和蛋白质，以理解生命本质并创新生物技术，构建非生命与生命物质间的联系，为医药、材料、制造、环境等领域提供创新解决方案。近年来，化学合成生物学迅速发展，成为化学、合成生物学领域的研究前沿与热点，非天然核酸、非天然氨基酸、正交遗传系统的开发取得了一系列的进展。研究者通过理论计算和实验验证，成功设计了一系列具有氢键特性的非天然碱基、镜像核酸，深化了生物与非生物关系的认知；通过非天然核酸和正交的tRNA/ 氨酰tRNA 合成酶干扰肽链延长步骤，将非天然氨基酸的插入从原核生物扩展至真核生物和多细胞生物，增加了生物分子的化学多样性；通过开发非天然核酸的聚合酶和连接酶，以及改造正交翻译系统的氨酰tRNA 合成酶和tRNA，构建了新型正交遗传系统，实现高效复制、转录与翻译。在使能技术的开发方面，非天然元件的设计与合成、正交遗传系统的设计、无细胞系统的开发与运用、人工智能在设计与测试等环节的运用，赋能化学合成生物学应用发展。这些基础研究与技术创新的发展，为诸多领域的开发提供了创新的解决方案，促成了应用领域的新发展。
通讯作者：张 宇 , Email:zy@ucas.ac.cn
Abstract:
Chemical synthetic biology, as a product of the intersection of chemistry and synthetic biology, holds significant importance in the engineered expansion of genetic codes and novel biochemical pathways. Chemical synthetic biology has rapidly advanced in recent years, emerging as a frontier and hotspot in the fields of chemistry and synthetic biology. By creating or modifying biological systems that do not exist in nature, synthesizing non-natural nucleic acids, amino acids, and proteins, it aims to understand the essence of life, innovate biotechnologies, establish connections between non-living and living matter, and provide innovative solutions for various fields such as medicine, materials, manufacturing, and environment. Researchers have made a series of advancements in the development of non-natural nucleotides, non-natural amino acids, and orthogonal genetic systems. Through theoretical calculations and experimental verification, they have successfully designed a series of non-natural bases and mirror nucleic acids with hydrogen bonding properties, deepening the understanding of the relationship between biological and non-biological entities. By interfering with the peptide elongation step using non-natural nucleotides and orthogonal tRNA/aminoacyl-tRNA synthetases, researchers have extended the insertion of non-natural amino acids from prokaryotes to eukaryotes and multicellular organisms, thereby increasing the chemical diversity of biomolecules. Through the development of non-natural nucleotide polymerases and ligases, as well as the modification of orthogonal translation systems' aminoacyl-tRNA synthetases and tRNAs, novel orthogonal genetic systems have been constructed, enabling efficient replication, transcription, and translation. In terms of technology development, the design and synthesis of non-natural components, the design of orthogonal genetic systems, the development and application of cell-free systems, and the utilization of artificial intelligence in design and testing processes empower the advancement of chemical synthetic biology applications. These advancements in basic research and technological innovation provide innovative solutions for various fields, facilitating new developments in application areas.
Communication Author：ZHANG Yu , Email:zy@ucas.ac.cn
