大肠杆菌代谢工程改造合成L-高丝氨酸及其衍生物研究进展

Advances in the biosynthesis of l-homoserine and its derivatives by metabolic engineering of Escherichia coli

摘要:

l-高丝氨酸及其衍生物(O-琥珀酰-l-高丝氨酸和O-乙酰-l-高丝氨酸)是生物合成l-甲硫氨酸的前体，同时也是合成多种C4化合物(异丁醇、g-丁内酯、1,4-丁二醇、2,4-二羟基丁酸等)和l-草铵膦等的平台化合物。因此，发酵法生产l-高丝氨酸及其衍生物成为近年内研究的热点。然而，利用生物法合成l-高丝氨酸及其衍生物仍存在一些不足之处，如发酵产量不高或糖酸转化率过低等。此外，对l-高丝氨酸及其衍生物合成的总体代谢和调控机制鲜有报道。本文综述了大肠杆菌代谢工程改造合成l-高丝氨酸及其衍生物O-琥珀酰-l-高丝氨酸和O-乙酰-l-高丝氨酸的研究进展，从底物摄取、关键节点碳流分配改造、辅酶NADPH的循环供应以及目标产物的外运输出等方面，系统分析了大肠杆菌全发酵法生产l-高丝氨酸及其衍生物的代谢途径及改造策略，为其后续代谢改造及生物法生产提供一定的研究思路。

Abstract:

l-homoserine and its derivatives (O-succinyl-l-homoserine and O-acetyl-l-homoserine) are precursors for the biosynthesis of l-methionine, and various C4 compounds (isobutanol, γ-butyrolactone, 1,4-butanediol, 2,4-dihydroxybutyric acid) and l-phosphinothricin. Therefore, the fermentative production of l-homoserine and its derivatives became the research hotspot in recent years. However, the low fermentation yield and conversion rate, and the unclear regulation mechanism for the biosynthesis of l-homoserine and its derivatives, hamper the development of an efficient production process for l-homoserine and its derivatives. This review summarized the advances in the biosynthesis of l-homoserine and its derivatives by metabolic engineering of Escherichia coli from the aspects of substrate uptake, redirection of carbon flow at the key nodes, recycle of NADPH and export of target products. This review may facilitate subsequent metabolic engineering and biotechnological production of l-homoserine and its derivatives.