scholarly journals An Overview of Bioprocesses Employing Specifically Selected Microbial Catalysts for γ-Aminobutyric Acid Production

2021 ◽  
Vol 9 (12) ◽  
pp. 2457
Author(s):  
Divakar Dahiya ◽  
Jemima V. Manuel ◽  
Poonam Singh Nigam

Gamma-aminobutyric acid (GABA) is an important chemical compound in the human brain. GABA acts as an inhibitory neurotransmitter by inducing hyperpolarization of cellular membranes. Usually, this pharmaceutically important compound is synthesized using a chemical process, but in this short overview we have only analysed microbial processes, which have been studied for the biosynthesis of this commercially important compound. The content of this article includes the following summarised information: the search for biological processes showed a number of lactic acid bacteria and certain species of fungi, which could be effectively used for the production of GABA. Strains found to possess GABA-producing pathways include Lactobacillus brevis CRL 1942, L. plantarum FNCC 260, Streptococcus salivarius subsp. thermophilus Y2, Bifidobacterium strains, Monascus spp., and Rhizopus spp. Each of these strains required specific growth conditions. However, several factors were common among these strains, such as the use of two main supplements in their fermentation medium—monosodium glutamate and pyridoxal phosphate—and maintaining an acidic pH. Optimization studies of GABA production were comprised of altering the media constituents, modifying growth conditions, types of cultivation system, and genetic manipulation. Some strains increased the production of GABA under anaerobic conditions. Genetic manipulation focused on silencing some genes or overexpression of gadB and gadC. The conclusion, based on the review of information available in published research, is that the targeted manipulation of selected microorganisms, as well as the culture conditions for an optimised bioprocess, should be adopted for an increased production of GABA to meet its increasing demand for food and pharmaceutical applications.

2021 ◽  
Vol 63 (1) ◽  
pp. 42-48
Author(s):  
Dai Hung Ngo ◽  
◽  
Quoc Tuan Tran ◽  
Thi Nhat Hang Nguyen ◽  
Dai Nghiep Ngo ◽  
...  

Gamma-aminobutyric acid (GABA) is a potent bioactive component that widely exists in both plants and animals, has numerous health benefits. This study aimed to optimise the fermentation process conditions for the growth of Lactobacillus fermentum from rice bran extracts that have high potential to produce GABA. GABA content was assessed by thin-layer chromatography (TLC) method. In this study, fermenting conditions for medium production of GABA by L. fermentum from rice bran extracts were optimised. L. fermentum showed high potential for GABA-producing ability. Some factors influencing the GABA production such as carbon sources, nitrogen sources, mineral salt sources, substrate concentration of monosodium glutamate (MSG), pH, and the time of fermentation were investigated. When the L. fermentum is cultivated in the rice bran extracts medium supplemented with 1.5% lactose, 2% yeast extract, and 1% MSG with pH 6.0 in 48 h, this strain showed high GABA at a concentration of 736 mg/l.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Patterson ◽  
P. M. Ryan ◽  
N. Wiley ◽  
I. Carafa ◽  
E. Sherwin ◽  
...  

Abstract Metabolic and neuroactive metabolite production represents one of the mechanisms through which the gut microbiota can impact health. One such metabolite, gamma-aminobutyric acid (GABA), can modulate glucose homeostasis and alter behavioural patterns in the host. We previously demonstrated that oral administration of GABA-producing Lactobacillus brevis DPC6108 has the potential to increase levels of circulating insulin in healthy rats. Therefore, the objective of this study was to assess the efficacy of endogenous microbial GABA production in improving metabolic and behavioural outcomes in a mouse model of metabolic dysfunction. Diet-induced obese and metabolically dysfunctional mice received one of two GABA-producing strains, L. brevis DPC6108 or L. brevis DSM32386, daily for 12 weeks. After 8 and 10 weeks of intervention, the behavioural and metabolic profiles of the mice were respectively assessed. Intervention with both L. brevis strains attenuated several abnormalities associated with metabolic dysfunction, causing a reduction in the accumulation of mesenteric adipose tissue, increased insulin secretion following glucose challenge, improved plasma cholesterol clearance and reduced despair-like behaviour and basal corticosterone production during the forced swim test. Taken together, this exploratory dataset indicates that intervention with GABA-producing lactobacilli has the potential to improve metabolic and depressive- like behavioural abnormalities associated with metabolic syndrome in mice.


Author(s):  
Sharmineh Sharafi ◽  
Leila Nateghi

Background and Objectives: Gamma-aminobutyric acid (GABA) is a non-protein four-carbon amino acid that has many physiological properties, including reducing blood pressure, accelerating protein synthesis in the brain, and treatment of insomnia and depression. This amino acid is produced by a number of lactic acid bacteria, fungi and yeasts. The objective of the present study was to identify probiotic bacteria with the maximum ability to generate GABA and optimize the bacterial culture conditions having the highest potential for GABA production. Materials and Methods: The potential of GABA production by Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus rhamnosus, Lactobacillus casei, Streptococcus thermophilus, Lactobacillus brevis and Lactococcus lactis ssp. lactis in the culture medium of MRS broth was assessed by High Performance Liquid Chromatography (HPLC). In order to increase the rate of GABA produced by the bacteria having the highest potential for GABA production, the conditions of the culture medium including pH (3.5 to 6.5) "temperature (25 to 45°C), time (12 to 96 h) and glutamic acid (GA) concentration (25 to 650 mmol) were optimized by the Box-Behnken’s Response Surface Method (RSM). Results: Lactobacillus brevis had the highest potential of GABA production (5960.8 mg/l). The effect of time and GA con- centration was significant on the amount of GABA production. The best conditions of culture medium to achieve the highest amount of GABA production by Lactobacillus brevis (19960 mg/l) were temperature 34.09°C, pH 4.65, GA concentration 650 mmol and time 96 h. Conclusion: The results showed that by optimization of the culture medium conditions of probiotic bacteria we can produce more GABA in culture medium


2019 ◽  
Vol 10 (5) ◽  
pp. 579-587 ◽  
Author(s):  
J.A. Valenzuela ◽  
A.B. Flórez ◽  
L. Vázquez ◽  
O.M. Vasek ◽  
B. Mayo

γ-Aminobutyric acid (GABA), an amino acid not used in protein synthesis, intervenes in several physiological functions and has both diuretic and calming effects in humans. Lactic acid bacteria (LAB) strains that produce GABA could be exploited for the manufacture of health-promoting GABA-enriched dairy products. In this study, 262 LAB strains isolated from traditional dairy products made from raw milk without starter cultures were screened for GABA production in culture media supplemented with 1% monosodium glutamate (MSG) using an enzymatic (GABase) method. About half of the strains (123) were found to be GABA producers. Of these, 24, among which were 16 Lactococcus lactis subsp. lactis and three Streptococcus thermophilus strains, produced >1 mM of GABA (range 1.01-2.81 mM) and were selected for further characterisation. GABA production was confirmed in most strains by culturing in 5 mM MSG followed by HPLC quantification. A majority of the strains were confirmed to be GABA producers by this method, although lower production levels were recorded. Using species-specific primers, the gene encoding glutamate decarboxylase (GAD) was PCR-amplified in all but one of the GABA producers analysed. Amplicons sequences were compared to one another and to those held in databases. Except for one Lactobacillus brevis strain, none of the 24 GABA producers investigated produced toxic biogenic amines, such as tyramine, histamine or cadaverine. They were therefore considered safe. Either alone, in mixtures, or in combination with industrial starter or adjunct cultures, these strains might be useful in the development of health-oriented dairy products.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Sagarika Banerjee ◽  
Matthew Poore ◽  
Svetlana Gerdes ◽  
Derek Nedveck ◽  
Lene Lauridsen ◽  
...  

Abstract Background Of the many neurotransmitters in humans, gamma-aminobutyric acid (GABA) shows potential for improving several mental health indications such as stress and anxiety. The microbiota-gut-brain axis is an important pathway for GABAergic effects, as microbially-secreted GABA within the gut can affect host mental health outcomes. Understanding the molecular characteristics of GABA production by microbes within the gut can offer insight to novel therapies for mental health. Results Three strains of Levilactobacillus brevis with syntenous glutamate decarboxylase (GAD) operons were evaluated for overall growth, glutamate utilization, and GABA production in typical synthetic growth media supplemented with monosodium glutamate (MSG). Levilactobacillus brevis Lbr-6108™ (Lbr-6108), formerly known as L. brevis DPC 6108, and Levilactobacillus brevis Lbr-35 ™ (Lbr-35) had similar growth profiles but differed significantly in GABA secretion and acid resistance. Lbr-6108 produced GABA early within the growth phase and produced significantly more GABA than Lbr-35 and the type strain Levilactobacillus brevis ATCC 14869 after the stationary phase. The global gene expression during GABA production at several timepoints was determined by RNA sequencing. The GAD operon, responsible for GABA production and secretion, activated in Lbr-6108 after only 6 h of fermentation and continued throughout the stationary phase. Furthermore, Lbr-6108 activated many different acid resistance mechanisms concurrently, which contribute to acid tolerance and energy production. In contrast, Lbr-35, which has a genetically similar GAD operon, including two copies of the GAD gene, showed no upregulation of the GAD operon, even when cultured with MSG. Conclusions This study is the first to evaluate whole transcriptome changes in Levilactobacillus brevis during GABA production in different growth phases. The concurrent expression of multiple acid-resistance mechanisms reveals niche-specific metabolic functionality between common human commensals and highlights the complex regulation of GABA metabolism in this important microbial species. Furthermore, the increased and rapid GABA production of Lbr-6108 highlights the strain’s potential as a therapeutic and the overall value of screening microbes for effector molecule output.


Catalysts ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 561 ◽  
Author(s):  
Kei-Anne Baritugo ◽  
Hee Taek Kim ◽  
Mi Na Rhie ◽  
Seo Young Jo ◽  
Tae Uk Khang ◽  
...  

Corynebacterium glutamicum is an industrial strain used for the production of valuable chemicals such as L-lysine and L-glutamate. Although C. glutamicum has various industrial applications, a limited number of tunable systems are available to engineer it for efficient production of platform chemicals. Therefore, in this study, we developed a novel tunable promoter system based on repeats of the Vitreoscilla hemoglobin promoter (Pvgb). Tunable expression of green fluorescent protein (GFP) was investigated under one, four, and eight repeats of Pvgb (Pvgb, Pvgb4, and Pvgb8). The intensity of fluorescence in recombinant C. glutamicum strains increased as the number of Pvgb increased from single to eight (Pvgb8) repeats. Furthermore, we demonstrated the application of the new Pvgb promoter-based vector system as a platform for metabolic engineering of C. glutamicum by investigating 5-aminovaleric acid (5-AVA) and gamma-aminobutyric acid (GABA) production in several C. glutamicum strains. The profile of 5-AVA and GABA production by the recombinant strains were evaluated to investigate the tunable expression of key enzymes such as DavBA and GadBmut. We observed that 5-AVA and GABA production by the recombinant strains increased as the number of Pvgb used for the expression of key proteins increased. The recombinant C. glutamicum strain expressing DavBA could produce higher amounts of 5-AVA under the control of Pvgb8 (3.69 ± 0.07 g/L) than the one under the control of Pvgb (3.43 ± 0.10 g/L). The average gamma-aminobutyric acid production also increased in all the tested strains as the number of Pvgb used for GadBmut expression increased from single (4.81–5.31 g/L) to eight repeats (4.94–5.58 g/L).


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