γ-氨基丁酸（GABA）具有多种生物学功能，已被列为新资源食品。 采用食品级微生物合成GABA是未来的发展趋势。本研究组分离的短乳杆菌NCL912发酵48h GABA达104g/L，具有应用前景。前期工作表明，Mn2+能显著提高NCL912的GABA合成能力（Li, et al. Amino Acids. 2010, 38: 1439-1445），但不影响负责合成GABA的谷氨酸脱羧酶(GAD)活性。推测其中存在受锰离子调控的效应基因，锰离子通过干预其差异表达发挥作用。本项目拟鉴定锰离子效应基因，揭示锰离子效应的遗传基础；对主效应基因进行改组，重塑基于锰离子的GABA合成控制网络，获取实用乳酸菌细胞工厂；优化影响GABA合成的胞外因子，使之与细胞的内在需求相协调，有效提升产物合成效率。旨在为深入研究GABA合成调控机制与菌种改造积累数据；为解析其它生物过程关键因子的遗传基础提供思路借鉴。

γ-aminobutyric acid (GABA) has a variety of biological functions, and has been listed as a new resource food. The synthesis of GABA by food-grade microorganisms will be the trend in the future. The GABA yield of Lactobacillus brevis NCL912, an our previously isolated strain, reaches 104g/L with 48 h of fermentation, showing a good application prospect. Preliminary work indicated that Mn2+ could significantly improve the GABA synthesis of NCL912 (Li, et al. Amino Acids. 2010, 38: 1439-1445), but did not affect the activity of glutamic acid decarboxylase (GAD) responsible for synthesizing GABA. We conjectured that there exist Mn2+ effect genes, and Mn2+ may play a role through regulating their differential expression. This project intends to identify the potential Mn2+ effect genes to reveal the genetic basis of the effect; shuffle the main Mn2+ effect genes, reconstruct the GABA synthesis control network based on Mn2+, and obtain a practical lactic acid bacterial cell factory; optimize extracellular factors affecting GABA synthesis to make them coordinate with the cell’s internal demand, and therefore effectively improve the efficacy of GABA production. Our goals are to accumulate data for in-depth study of the GABA synthesis regulation mechanism and stain modification; and provide the reference for resolving the genetic basis of key factors of other biological processes.