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      Recent advances in the biosynthesis and industrial biotechnology of Gamma-amino butyric acid

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          Abstract

          GABA (Gamma-aminobutyric acid), a crucial neurotransmitter in the central nervous system, has gained significant attention in recent years due to its extensive benefits for human health. The review focused on recent advances in the biosynthesis and production of GABA. To begin with, the investigation evaluates GABA-producing strains and metabolic pathways, focusing on microbial sources such as Lactic Acid Bacteria, Escherichia coli, and Corynebacterium glutamicum. The metabolic pathways of GABA are elaborated upon, including the GABA shunt and critical enzymes involved in its synthesis. Next, strategies to enhance microbial GABA production are discussed, including optimization of fermentation factors, different fermentation methods such as co-culture strategy and two-step fermentation, and modification of the GABA metabolic pathway. The review also explores methods for determining glutamate (Glu) and GABA levels, emphasizing the importance of accurate quantification. Furthermore, a comprehensive market analysis and prospects are provided, highlighting current trends, potential applications, and challenges in the GABA industry. Overall, this review serves as a valuable resource for researchers and industrialists working on GABA advancements, focusing on its efficient synthesis processes and various applications, and providing novel ideas and approaches to improve GABA yield and quality.

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          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40643-024-00747-7.

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          Most cited references197

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          Metabolism and functions of gamma-aminobutyric acid.

          B. Shelp (1999)
          Gamma-aminobutyric acid (GABA), a four-carbon non-protein amino acid, is a significant component of the free amino acid pool in most prokaryotic and eukaryotic organisms. In plants, stress initiates a signal-transduction pathway, in which increased cytosolic Ca2+ activates Ca2+/calmodulin-dependent glutamate decarboxylase activity and GABA synthesis. Elevated H+ and substrate levels can also stimulate glutamate decarboxylase activity. GABA accumulation probably is mediated primarily by glutamate decarboxylase. However, more information is needed concerning the control of the catabolic mitochondrial enzymes (GABA transaminase and succinic semialdehyde dehydrogenase) and the intracellular and intercellular transport of GABA. Experimental evidence supports the involvement of GABA synthesis in pH regulation, nitrogen storage, plant development and defence, as well as a compatible osmolyte and an alternative pathway for glutamate utilization. There is a need to identify the genes of enzymes involved in GABA metabolism, and to generate mutants with which to elucidate the physiological function(s) of GABA in plants.
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            Highway or byway: the metabolic role of the GABA shunt in plants.

            Much of the recent work on the gamma-aminobutyrate (GABA) shunt in plants has concentrated on stress/pest-associated and signalling roles. However, fifty years after the structural elucidation of the pathway, aspects of its regulation and even of its biological significance remain largely obscure. Here, we assess the importance of GABA metabolism in plants, reviewing relevant biological circumstances and taking advantage of high-throughput data accessibility and computational approaches. We discuss the premise that GABA metabolism plays a major role in carbon and nitrogen primary metabolism. We further evaluate technological developments that will likely allow us to address the quantitative importance of this shunt within the biological processes to which it contributes.
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              The GABAergic deficit hypothesis of major depressive disorder.

              Increasing evidence points to an association between major depressive disorders (MDDs) and diverse types of GABAergic deficits. In this review, we summarize clinical and preclinical evidence supporting a central and causal role of GABAergic deficits in the etiology of depressive disorders. Studies of depressed patients indicate that MDDs are accompanied by reduced brain concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and by alterations in the subunit composition of the principal receptors (GABA(A) receptors) mediating GABAergic inhibition. In addition, there is abundant evidence that suggests that GABA has a prominent role in the brain control of stress, the most important vulnerability factor in mood disorders. Furthermore, preclinical evidence suggests that currently used antidepressant drugs (ADs) designed to alter monoaminergic transmission and nonpharmacological therapies may ultimately act to counteract GABAergic deficits. In particular, GABAergic transmission has an important role in the control of hippocampal neurogenesis and neural maturation, which are now established as cellular substrates of most if not all antidepressant therapies. Finally, comparatively modest deficits in GABAergic transmission in GABA(A) receptor-deficient mice are sufficient to cause behavioral, cognitive, neuroanatomical and neuroendocrine phenotypes, as well as AD response characteristics expected of an animal model of MDD. The GABAergic hypothesis of MDD suggests that alterations in GABAergic transmission represent fundamentally important aspects of the etiological sequelae of MDDs that are reversed by monoaminergic AD action.
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                Author and article information

                Contributors
                renlujing@njtech.edu.cn
                Journal
                Bioresour Bioprocess
                Bioresour Bioprocess
                Bioresources and Bioprocessing
                Springer Nature Singapore (Singapore )
                2197-4365
                16 March 2024
                16 March 2024
                December 2024
                : 11
                : 1
                : 32
                Affiliations
                [1 ]College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, ( https://ror.org/03sd35x91) No. 30 South Puzhu Road, Nanjing, 211816 People’s Republic of China
                [2 ]Shanghai JanStar Technology Development Co, Ltd., No. 1288, Huateng Road, Shanghai, People’s Republic of China
                Author information
                http://orcid.org/0000-0002-6217-7309
                Article
                747
                10.1186/s40643-024-00747-7
                10992975
                c56c18d1-9fe4-430c-995a-5c5ca609cc3e
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 December 2023
                : 3 March 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100012165, Key Technologies Research and Development Program;
                Award ID: 2019YFA0905700
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 21878151
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;
                Award ID: BK20211535
                Award Recipient :
                Funded by: Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture
                Award ID: XTD2213
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100018592, “333 Project” of Jiangsu Province;
                Award ID: 2022
                Award Recipient :
                Categories
                Review
                Custom metadata
                © State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology 2024

                gamma-aminobutyric acid,biosynthesis,microbial production,fermentation optimization,metabolic pathways

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