School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, China.
School of Life Sciences, Nanjing Normal University, Nanjing, China.
Crit Rev Biotechnol. 2023 Sep;43(6):938-955. doi: 10.1080/07388551.2022.2090314. Epub 2022 Aug 22.
Cell-free synthesis systems can complete the transcription and translation process to produce complex proteins that are difficult to be expressed in traditional cell-based systems. Such systems also can be used for the assembly of efficient localized multienzyme cascades to synthesize products that are toxic to cells. Cell-free synthesis systems provide a simpler and faster engineering solution than living cells, allowing unprecedented design freedom. This paper reviews the latest progress on the application of cell-free synthesis systems in the field of enzymatic catalysis, including cell-free protein synthesis and cell-free metabolic engineering. In cell-free protein synthesis: complex proteins, toxic proteins, membrane proteins, and artificial proteins containing non-natural amino acids can be easily synthesized by directly controlling the reaction conditions in the cell-free system. In cell-free metabolic engineering, the synthesis of desired products can be made more specific and efficient by designing metabolic pathways and screening biocatalysts based on purified enzymes or crude extracts. Through the combination of cell-free synthesis systems and emerging technologies, such as: synthetic biology, microfluidic control, cofactor regeneration, and artificial scaffolds, we will be able to build increasingly complex biomolecule systems. In the next few years, these technologies are expected to mature and reach industrialization, providing innovative platforms for a wide range of biotechnological applications.
无细胞合成系统可以完成转录和翻译过程,从而产生传统基于细胞的系统难以表达的复杂蛋白质。此类系统还可用于高效局部多酶级联的组装,以合成对细胞有毒的产物。与活细胞相比,无细胞合成系统提供了更简单、更快的工程解决方案,从而实现了前所未有的设计自由度。本文综述了无细胞合成系统在酶催化领域的最新应用进展,包括无细胞蛋白合成和无细胞代谢工程。在无细胞蛋白合成中:通过直接控制无细胞系统中的反应条件,可以轻松合成复杂蛋白、毒性蛋白、膜蛋白和含有非天然氨基酸的人工蛋白。在无细胞代谢工程中,可以通过基于纯化酶或粗提物设计代谢途径和筛选生物催化剂,使所需产物的合成更具特异性和高效性。通过无细胞合成系统与新兴技术(如合成生物学、微流控控制、辅因子再生和人工支架)的结合,我们将能够构建越来越复杂的生物分子系统。在未来几年中,这些技术有望成熟并实现工业化,为广泛的生物技术应用提供创新平台。