非天然氨基酸细胞工厂的构建与应用

Construction and application of microbial cell factories for unnatural amino acids

非天然氨基酸在医药、农药、材料等领域得到广泛应用,其绿色、高效合成越来越受到关注。近年来,随着合成生物学的快速发展,微生物细胞工厂为非天然氨基酸的制造提供了重要手段。文中从合成途径的重构、关键酶的设计改造及与前体的协同调控、竞争性旁路途径的敲除、辅因子循环系统的构建等方面介绍了一系列非天然氨基酸细胞工厂构建与应用的研究进展,并从基于计算机深度学习的非天然氨基酸微生物细胞工厂设计新原则、与细胞和环境相适配的生物合成新途径,以及基于细胞适应性进化和智能发酵调控的生物制造新体系等方面对非天然氨基酸细胞工厂的进一步构建和应用进行了展望,提出了非天然氨基酸绿色、高效工业化生产的重要前景。

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.