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Biotechnological advances and perspectives of gamma-aminobutyric acid production

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Abstract

Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that is widely distributed among various organisms. Since GABA has several well-known physiological functions, such as mediating neurotransmission and hypotensive activity, as well as having tranquilizer effects, it is commonly used as a bioactive compound in the food, pharmaceutical and feed industries. The major pathway of GABA biosynthesis is the irreversible decarboxylation of l-glutamate catalyzed by glutamate decarboxylase (GAD), which develops a safe, sustainable and environmentally friendly alternative in comparison with traditional chemical synthesis methods. To date, several microorganisms have been successfully engineered for high-level GABA biosynthesis by overexpressing exogenous GADs. However, the activity of almost all reported microbial GADs sharply decreases at physiological near-neutral pH, which in turn provokes negative effects on the application of these GADs in the recombinant strains for GABA production. Therefore, ongoing efforts in the molecular evolution of GADs, in combination with high-throughput screening and metabolic engineering of particular producer strains, offer fascinating new prospects for effective, environmentally friendly and economically viable GABA biosynthesis. In this review, we briefly introduce the applications in which GABA is used, and summarize the most important methods associated with GABA production. The major achievements and present challenges in the biotechnological synthesis of GABA, focusing on screening and enzyme engineering of GADs, as well as metabolic engineering strategy for one-step GABA biosynthesis, will be extensively discussed.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 31500044) and the “Hundred Talents Program” of the Chinese Academy of Sciences.

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  1. Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People’s Republic of China

    Ning Xu, Liang Wei & Jun Liu

  2. Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People’s Republic of China

    Ning Xu & Jun Liu

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  1. Ning Xu
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Correspondence to Jun Liu.

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Xu, N., Wei, L. & Liu, J. Biotechnological advances and perspectives of gamma-aminobutyric acid production. World J Microbiol Biotechnol 33, 64 (2017). https://doi.org/10.1007/s11274-017-2234-5

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