谷氨酸棒杆菌(Corynebacterium glutamicum)生产L-缬氨酸的代谢工程研究

L-缬氨酸是人体必需氨基酸，广泛应用于食品、医药及饲料等行业，在国内外市场上供不应求。目前L-缬氨酸发酵生产主要采用传统诱变育种得到的谷氨酸棒杆菌(Corynebacterium glutamicum)，这些菌的L-缬氨酸产量较低而杂酸较高，迫切需要进行代谢工程优化。但是C. glutamicum中L-缬氨酸的生物合成途径相当复杂，且受到产物反馈抑制和转录调控，为代谢工程改造增加了难度。本项目拟利用C. glutamicum的基因组信息，结合转录组学，从阻止杂酸合成、积累关键前体物质、解除反馈抑制和增加产物分泌等方面对C. glutamicum 进行代谢工程定向改造，使其能够最大限度地合成并分泌L-缬氨酸。本项目研究不仅有利于C. glutamicum L-缬氨酸发酵生产,而且对其它氨基酸工业生产菌的代谢工程改造具有重要的指导作用。

L-valine, an essential amino acid for human, is widely demanded the domestic and foreign markets in products of food, medicine and feed. L-valine is mainly produced by Corynebacterium glutamicum obtained by traditional mutagenesis，in which the L-valine yield is not high enough. Therefore, there is an urgent need for metabolic engineering optimization of the bacterium to increase its L-valine production. However, the biosynthesis pathway of L-valine in C. glutamicum are complex, and transcriptionally regulated and inhibited by L-valine, making the metabolic engineering research more difficult. This project will carry out metabolic engineering to increase L-valine production in C. glutamicum, using transcriptomics, proteomics and metabolomics to accumulate the key precursors, to break the feedback inhibition, and to increase L-valine secretion.The results would be useful for modifying industrial bacteria for production of other amino acids.