γ-氨基丁酸（GABA）是哺乳动物体内主要的抑制性神经递质，具有多种重要的生物学功能，已被批准为新资源食品。利用食品级微生物合成GABA是一种新型绿色技术。短乳杆菌NCL912发酵48h GABA达104g/L（Li, et al. Microb Cell Fact. 2010, 9: 85），具有应用前景。然而，前期工作发现NCL912同时具有GABA降解能力，导致产物浓度降低。推测其中存在GABA代谢支路（三羧酸循环的侧支），将GABA转化为琥珀酸。本项目拟解析NCL912 GABA代谢支路的遗传基础；阐明该支路与三羧酸循环的关联；敲除GABA代谢支路，并强化TCA循环，构建高产GABA基因工程菌；研究菌种的发酵特性，优化培养条件，并通过发酵调控进一步提升产物积累能力。旨在为进一步改造菌种、代谢调控以及阐明GABA的生理功能积累数据；为揭示其它乳酸菌GABA代谢支路提供思路借鉴。

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in mammals, with a variety of important biological functions, and has been approved as a new resource food. The synthesis of GABA by food grade microorganisms is a new green technology. The GABA production of Lactobacillus brevis NCL912, an our previously isolated strain, reaches 104g/L with 48 h of fermentation (Li, et al. Microb Cell Fact. 2010, 9: 85), showing a good application prospect. However, our previous studies found that NCL912 also has the ability of degrading GABA, resulting in decrease in concentration of GABA. We speculated that GABA shunt exists in NCL912 (a collateral of tricarboxylic acid cycle), which converts GABA into succinate. This project aims to identify the genetic basis of GABA shunt in NCL912; elucidate the inherent correlation of the shunt and tricarboxylic acid cycle; construct a high-GABA yielding genetically engineered strain by knocking out the GABA shunt and strengthening the tricarboxylic acid cycle; research fermentation characteristics of the strain, optimize its culture conditions, and further enhance the strain’s ability of GABA accumulation through fermentation regulation. Our goals are to accumulate data for further strain modification, metabolic regulation and clarification of GABA’s physiological functions; and offer the reference to reveal GABA shunts of the other lactic acid bacteria.