Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), BioProcess Engineering Research Center, and Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea.
Biotechnol J. 2010 Jun;5(6):560-77. doi: 10.1002/biot.201000032.
The L-aspartate family amino acids (AFAAs), L-threonine, L-lysine, L-methionine and L-isoleucine have recently been of much interest due to their wide spectrum of applications including food additives, components of cosmetics and therapeutic agents, and animal feed additives. Among them, L-threonine, L-lysine and L-methionine are three major amino acids produced currently throughout the world. Recent advances in systems metabolic engineering, which combine various high-throughput omics technologies and computational analysis, are now facilitating development of microbial strains efficiently producing AFAAs. Thus, a thorough understanding of the metabolic and regulatory mechanisms of the biosynthesis of these amino acids is urgently needed for designing system-wide metabolic engineering strategies. Here we review the details of AFAA biosynthetic pathways, regulations involved, and export and transport systems, and provide general strategies for successful metabolic engineering along with relevant examples. Finally, perspectives of systems metabolic engineering for developing AFAA overproducers are suggested with selected exemplary studies.
L-天冬氨酸族氨基酸（AFAAs）、L-苏氨酸、L-赖氨酸、L-蛋氨酸和 L-异亮氨酸由于其广泛的应用而备受关注，包括食品添加剂、化妆品成分和治疗剂以及动物饲料添加剂。其中，L-苏氨酸、L-赖氨酸和 L-蛋氨酸是目前全球产量最大的三种氨基酸。系统代谢工程的最新进展结合了各种高通量组学技术和计算分析，现在正在促进高效生产 AFAAs 的微生物菌株的开发。因此，为了设计全面的代谢工程策略，迫切需要深入了解这些氨基酸生物合成的代谢和调控机制。在这里，我们综述了 AFAAs 生物合成途径、涉及的调控以及出口和运输系统的详细信息，并提供了成功进行代谢工程的一般策略及其相关实例。最后，我们提出了通过系统代谢工程开发 AFAAs 高产菌的观点，并选择了一些具有代表性的研究进行了讨论。
