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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (8): 110-119    DOI: 10.13523/j.cb.2103038
综述     
生物法合成γ-氨基丁酸的研究策略*
张恒1,2,刘慧燕1,2,潘琳1,2,王红燕1,2,李晓芳1,2,王彤1,2,方海田1,2,**()
1 宁夏大学食品与葡萄酒学院 银川 750021
2 宁夏食品微生物应用技术与安全控制重点实验室 银川 750021
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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摘要：

γ-氨基丁酸(γ-aminobutyric acid,GABA)是一种极易溶于水的非蛋白质氨基酸,被广泛应用于食品和制药工业中,市场需求量极大。可通过化学合成法、植物富集法、微生物直接发酵法和生物转化法生产。近年来,因生物法合成GABA具有相对优势,受到研究者们的重视。对GABA的生产方法、生产GABA的微生物、微生物合成GABA的关键代谢途径和GAD酶的定向改造策略进行了论述。
关键词： γ-氨基丁酸;  生物合成;  代谢途径;  定向改造    
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
收稿日期: 2021-03-17 出版日期: 2021-08-31
ZTFLH:  Q816  
基金资助: * 宁夏回族自治区重点研发计划(2019BCH01002);宁夏食品微生物应用技术与安全控制重点实验室平台建设项目资助项目(2019BDC05009);宁夏食品微生物应用技术与安全控制重点实验室平台建设项目资助项目(2019YDDF0062)
通讯作者: 方海田     E-mail: fanght@nxu.edu.cn
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张恒
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李晓芳
王彤
方海田

引用本文:

张恒,刘慧燕,潘琳,王红燕,李晓芳,王彤,方海田. 生物法合成γ-氨基丁酸的研究策略*[J]. 中国生物工程杂志, 2021, 41(8): 110-119.

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.

链接本文:

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

图1  γ-氨基丁酸的化学结构式
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]
表1  不同来源微生物的生长条件及GAD酶学特性
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]
表2  常见生产GABA的微生物及生产方法
图2  大肠杆菌GABA代谢途径及编码基因
图3  谷氨酸棒杆菌谷氨酸代谢途径
图4  PLP活性中心
图5  酸性和中性条件下gad B蛋白质结构图
图6  62号氨基酸突变前后与PLP的相互作用图
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