Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma-aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma-aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to.

BackgroundGamma-aminobutyric acid is a major inhibitory neurotransmitter in mammalian brains, and has several well-known physiological functions. Lactic acid bacteria possess special physiological activities and are generally regarded as safe. Therefore, using lactic acid bacteria as cell factories for gamma-aminobutyric acid production is a fascinating project and opens up a vast range of prospects for making use of GABA and LAB. We previously screened a high GABA-producer Lactobacillus brevis NCL912 and optimized its fermentation medium composition. The results indicated that the strain showed potential in large-scale fermentation for the production of gamma-aminobutyric acid. To increase the yielding of GABA, further study on the fermentation process is needed before the industrial application in the future. In this article we investigated the impacts of pyridoxal-5'-phosphate, pH, temperature and initial glutamate concentration on gamma-aminobutyric acid production by Lactobacillus brevis NCL912 in flask cultures. According to the data obtained in the above, a simple and effective fed-batch fermentation method was developed to highly efficiently convert glutamate to gamma-aminobutyric acid.ResultsPyridoxal-5'-phosphate did not affect the cell growth and gamma-aminobutyric acid production of Lb. brevis NCL912. Temperature, pH and initial glutamate concentration had significant effects on the cell growth and gamma-aminobutyric acid production of Lb. brevis NCL912. The optimal temperature, pH and initial glutamate concentration were 30-35°C, 5.0 and 250-500 mM. In the following fed-batch fermentations, temperature, pH and initial glutamate concentration were fixed as 32°C, 5.0 and 400 mM. 280.70 g (1.5 mol) and 224.56 g (1.2 mol) glutamate were supplemented into the bioreactor at 12 h and 24 h, respectively. Under the selected fermentation conditions, gamma-aminobutyric acid was rapidly produced at the first 36 h and almost not produced after then. The gamma-aminobutyric acid concentration reached 1005.81 ± 47.88 mM, and the residual glucose and glutamate were 15.28 ± 0.51 g L-1 and 134.45 ± 24.22 mM at 48 h.ConclusionsA simple and effective fed-batch fermentation method was developed for Lb. brevis NCL912 to produce gamma-aminobutyric acid. The results reveal that Lb. brevis NCL912 exhibits a great application potential in large-scale fermentation for the production of gamma-aminobutyric acid.

To find a high γ-aminobutyric acid-producing lactic acid bacterium, more than 1000 strains of lactic acid bacteria isolated from paocai samples in various areas of China were screened by the ability in production of γ-aminobutyric acid, analysed with paper chromatography, HPLC and HPLC-MS. Among them, one strain NCL912 exhibited high ability to convert sodium glutamate to γ-aminobutyric acid. The strain accumulated 149.05 mM of γ-aminobutyric acid in a modified MRS medium containing 3% sodium glutamate after 48 h of static cultivation at 30 °C. This strain was identified as Lactobacillus brevis according to its phenotypic and phylogenetic characteristics.

Production of gamma-aminobutyric acid (GABA) was carried out in Erlenmeyer flasks by Lactobacillus brevis NCL912. Traditional methods were first adopted to select the key factors that impact the GABA production to preliminarily determine the suitable concentration ranges of the key factors. It was found that glucose, soya peptone, Tween-80 and MnSO(4).4H(2)O were the key factors affecting GABA production. Then, response surface methodology was applied to analyze the optimum contents of the four key factors in the medium, and the production of GABA was predicted as 349.69 mM under the optimized conditions with this model. Afterward, the experiment was performed under the optimized conditions, and the yield of GABA reached 345.83 mM, which was 130% higher than the initial medium. The results showed that experimental yield and predicted values of GABA yield were in good agreement.

No abstract

No abstract

Both thioredoxin-interacting protein (TXNIP) and endoplasmic reticulum (ER) stress are implicated in skeletal muscle insulin resistance. Icariin has been found to mimic insulin action in normal skeletal muscle C2C12 cells and display anti-diabetic properties in diet-induced obese mice. However, the underlying molecular mechanism remains to be well-established. Herein, we tested the hypothesis that the protective effects of icariin on free fatty acid-induced insulin resistance were attributed to its regulation on TXNIP protein levels and ER stress in skeletal muscle cells. We found that TXNIP mediated the saturated fatty acid palmitate (PA)-induced insulin resistance in C2C12 myotubes. Icariin treatment significantly restored PA-reduced proteasome activity resulting in reduction of TXNIP protein and suppression of ER stress, as well as improvement of insulin sensitivity. Proteasome inhibition by its specific inhibitor MG132 obviously abolished the inhibitory effect of icariin on PA-induced insulin resistance. In addition, MG132 supplementation markedly abrogated the impacts of icariin on ER stress and TXNIP-mediated downstream events such as inflammation and STAT3 phosphorylation. These results clearly indicate that icariin improves PA-induced skeletal muscle insulin resistance through a proteasome-dependent mechanism, by which icariin downregulats TXNIP levels and inhibits ER stress.

No abstract