谷氨酸棒杆菌和大肠杆菌生物合成L-甲硫氨酸的代谢工程改造研究进展

Recent Advances in L-Methionine Biosynthesis in Metabolically Engineered Corynebacterium glutamicum and Escherichia coli

L-甲硫氨酸是生命体必需的唯一含硫氨基酸,其作为前体参与合成多种生物活性物质,并参与机体多种代谢,被广泛应用于食品、动物饲料、药品、化妆品等领域。由于L-甲硫氨酸是唯一无法用微生物发酵法工业化生产的必需氨基酸,近年来,利用代谢工程提升L-甲硫氨酸产量受到国内外研究人员的普遍重视。本文主要分析并比较在谷氨酸棒杆菌和大肠杆菌中L-甲硫氨酸的生物合成途径及代谢调控网络机制;分别从解除代谢途径对关键酶的反馈作用、阻断或削弱支路代谢途径、中心代谢调控网络的优化、增强辅助因子的供应以及转运系统的优化这5个方面综述L-甲硫氨酸代谢工程改造策略,总结L-甲硫氨酸的生物合成研究进展并作展望,旨在为L-甲硫氨酸高产发酵菌株的选择提供依据。

L-Methionine is the only sulfur-containing essential amino acid.It acts as a precursor in the synthesis of various biologically active substances and participates in various metabolic pathways in the body.It is widely used in food,animal feed,medicine,cosmetics,and other fields.In recent years,since L-methionine is the only essential amino acid that cannot be industrially produced by microbial fermentation,the potential of metabolic engineering to improve L-methionine production has received widespread attention from researchers around the world.In this paper,the biosynthesis pathways and metabolic regulation mechanisms of L-methionine in Corynebacterium glutamicum and Escherichia coli are analyzed and compared.The metabolic engineering strategies to produce L-methionine are reviewed from five aspects:the removal of feedback inhibition of key enzymes,the cut-off or weakening of branch metabolic pathways,the optimization of the central metabolic regulatory network,the enhancement of cofactor supply,and the optimization of transport systems,and recent progress in research on the biosynthesis of L-methionine is summarized.Finally,future prospects are also discussed.It is hoped that this review will provide a basis for the breeding of high-yield L-methionine-producing strains.