PDF(Pubmed)
Abstract：
The phosphoenol pyruvate-oxaloacetate-pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate-oxaloacetate-pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate-oxaloacetate-pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed.
摘要：
磷酸烯醇丙酮酸-草酰乙酸-丙酮酸衍生的氨基酸（POP-AA）是细胞代谢中的天然中间体，其中磷酸烯醇丙酮酸-草酰乙酸-丙酮酸（POP）节点是大多数生物体中存在的主要代谢途径之间的转换点。POP-AA在营养学中有着广泛的应用,食物,和制药行业。这些氨基酸主要通过微生物发酵在大肠杆菌和谷氨酸棒杆菌中产生。随着市场需求的迅速增加,随着全球粮食短缺的形势，这两种细菌的工业生产能力遇到了两个瓶颈:产品转化效率低和原材料成本高。旨在推动具有更高产量和生产率的工程菌株的更新和升级，本文全面总结了磷酸烯醇丙酮酸-草酰乙酸-丙酮酸节点的代谢工程技术的基本策略，包括L-色氨酸,L-酪氨酸,L-苯丙氨酸,L-缬氨酸,L-赖氨酸,L-苏氨酸,和L-异亮氨酸.应考虑关于POP节点中碳通量再分布和氨基酸形成的新的异源途径和调节方法，以提高POP-AA的产量，使其接近最大理论值。此外，展望了未来低成本原料和能源利用发展氨基酸过剩生产者的战略。
