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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2021, Vol. 41 Issue (8): 110-119    DOI: 10.13523/j.cb.2103038
    
Research Strategy for Biosynthesis of Gamma Aminobutyric Acid
ZHANG Heng1,2,LIU Hui-yan1,2,PAN Lin1,2,WANG Hong-yan1,2,LI Xiao-fang1,2,WANG Tong1,2,FANG Hai-tian1,2,**()
1 School of Food and Wine, Ningxia University, Yinchuan 750021, China
2 Ningxia Key Laboratory for Food Microbial-Applications Technology and Safety Control, Ningxia University, Yinchuan 750021, China
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Abstract  

Gamma aminobutyric acid (GABA) is a kind of non-protein amino acid which is very soluble in water. It is widely used in food and pharmaceutical industry, and the market demand is very large. It can be produced by chemical synthesis, plant enrichment, microbial direct fermentation and biotransformation. In recent years, the synthesis of GABA by biological methods has its relative advantages, and has been paid attention by researchers. In this paper, the production methods of GABA, the microorganisms producing GABA, the key metabolic pathway of GABA synthesis and the directed transformation strategy of GAD enzyme were discussed.

Key words： γ-Aminobutyric acid      Biosynthesis      Metabolic pathway      Directed transformation     
Received: 17 March 2021      Published: 31 August 2021
ZTFLH:  Q816  
Corresponding Authors: Hai-tian FANG     E-mail: fanght@nxu.edu.cn
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Heng ZHANG
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Cite this article:

ZHANG Heng,LIU Hui-yan,PAN Lin,WANG Hong-yan,LI Xiao-fang,WANG Tong,FANG Hai-tian. Research Strategy for Biosynthesis of Gamma Aminobutyric Acid. China Biotechnology, 2021, 41(8): 110-119.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2103038     OR     https://manu60.magtech.com.cn/biotech/Y2021/V41/I8/110

Fig.1 The chemical structure formula of GABA
来源 生长条件 GAD特性 参考文献
最适温度/℃ 最适pH 最适温度/℃ 最适pH
大肠杆菌(细菌) 37 6.0~6.5 37 3.8~4.5 [14]
短乳杆菌(细菌) 37 5.5~6.0 50 4.0~4.5 [15]
酵母菌(真菌) 25 5.0~5.5 35 5.0~5.5 [16]
米曲霉(真菌 ) 30 6.0~6.5 40 5.0~5.5 [7]
Table 1 Growth conditions of microorganisms from different sources and GAD enzymatic characteristics
微生物 生产方法 底物 GABA产量/
(g/L)		 参考文献
大肠杆菌
E.coli K-12 蛋白质支架固定GABA分流通路的关键酶,直接发酵 10 g/L的葡萄糖 1.08 [18]
E.coli BL21(DE3) E.coli K-12的GAD表达于E.coli BL2,全细胞转化 200 g/L的L-谷氨酸 138 [19]
E.coli BW25113 Lactococcus lactis的GAD定点突变后表达于E. coli BW25113。全细胞转化 441.39 g/L的L-谷
氨酸		 307.4 [20]
E.coli XL1-Blue (XB) Thermococcus hordei的GAD异源表达于E.coli XL1-Blue (XB),直接发酵 10 g/L的味精 5.69 [21]
乳酸菌
L.plantarum UV43-7 诱变所得菌株,直接发酵 15 g/L的味精 4.003 [22]
L. plantarum CICC 6238 诱变所得菌株,直接发酵 15 g/L的味精 1.196±0.033 [23]
Lactobacillus paracasei 直接发酵 73.57 g/L的L-谷氨酸 31.11 [24]
谷氨酸棒杆菌
C.glutamicum ATCC
13032		 E.coli K-12的GAD表达于C.glutamicum ATCC,直接发酵 50 g/L的葡萄糖 12 [25]
C.glutamicum ATCC
13032		 L.plantarum GB01-21的 GAD定点突变后异源表达于C.glutamicum ATCC13032,全细胞转化 400 g/L的L-谷氨酸 116 [26]
Table 2 Methods and yield of GABA production by various microorganisms
Fig.2 GABA metabolic pathway and coding genes in Escherichia coli
Fig.3 Glutamate metabolism pathway in Corynebacterium glutamicum
Fig.4 PLP active center
Fig.5 gad B protein structure under acidic and neutral conditions (a)Conformation under neutral conditions (b)Conformation under acidic conditions
Fig.6 Interaction map of amino acid 62 with PLP before and after mutation (a)Before mutation (b)After mutation
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