Tang Xiaoling, Zhang Huimin, Liu Zhiqiang, Zheng Yuguo
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
Sheng Wu Gong Cheng Xue Bao. 2022 Apr 25;38(4):1295-1306. doi: 10.13345/j.cjb.210505.
Unnatural amino acids are widely used in medicine, pesticide, material, and other industries and the green and efficient synthesis has attracted a lot of attention. In recent years, with the rapid development of synthetic biology, microbial cell factories have become a promising means for biosynthesis of unnatural amino acids. This study reviewed the construction and application of microbial cell factories for unnatural amino acid, including the synthetic pathway reconstruction, design/modification of key enzymes and their coordinated regulation with precursors, blocking of competitive alternative pathways, and construction of cofactor circulation systems. Meanwhile, on the basis of the new principles for designing the microbial cell factories, new biosynthetic pathways adapted to cells and the production environment, as well as new biomanufacturing system established based on cell adaptive evolution and intelligent fermentation regulation, we looked forward to the further construction and application of microbial cell factories for industrial bio-production.
非天然氨基酸在医药、农药、材料等行业有着广泛应用，其绿色高效合成备受关注。近年来，随着合成生物学的快速发展，微生物细胞工厂已成为非天然氨基酸生物合成的一种有前景的手段。本研究综述了用于非天然氨基酸合成的微生物细胞工厂的构建与应用，包括合成途径重构、关键酶的设计/修饰及其与前体的协同调控、竞争性替代途径的阻断以及辅因子循环系统的构建。同时，基于设计微生物细胞工厂的新原理、适应细胞和生产环境的新生物合成途径以及基于细胞适应性进化和智能发酵调控建立的新生物制造系统，我们展望了用于工业生物生产的微生物细胞工厂的进一步构建与应用。
