ABSTRACT
Non-proteinaceous amino acid gamma amino butyric acid (GABA) serves as an inhibitory neurotransmitter in the mammalian nervous system. The synthesis of gamma amino butyric acid (GABA) by several Lactobacillus species in various fermented food products was examined in this review work in relation to culture conditions, including carbon and nitrogen supplies, L-monosodium glutamate (MSG) and starting pH. GABA is involved in a variety of physiological processes, including reducing anxiety and menopausal symptoms, treating stress and hypertension, boosting immunity, treating insomnia and depression, regulating blood pressure, enhancing visual cortical function and preventing diabetes. Most GABA is produced through the fermentation of microbes such as yeast, fungus and bacteria. Lactic acid bacteria (LAB) are one of the microorganisms that are utilized in the production of GABA and are frequently found in many fermented foods. The discussion in this review will be split into two sections: one will highlight research on fermented food products using various Lactobacillus species and the other will highlight the generation of GABA using Lactobacillus species. It is safer to use than other technologies because it makes use of environmentally favourable and safe microorganisms for production.
1. INTRODUCTION
Gamma Amino butyric acid or GABA is a chemical compound with the molecular weight of 103.12 gmol-1 and the chemical formula C4H9NO2. (1991, Florey E. GABA (gamma-aminobutyric acid) is a non-protein amino acid that is found in a wide variety of creatures, including plants, animals and microbes. Particularly in various brain areas, GABA is found in significant amounts. (2006) Olsen et al. A significant amount of GABA was found to be secreted by the mammalian central nervous system (CNS) in 1950. The first natural GABA was discovered as a component of potato tuber tissue. (1949; Steward et al.). Glutamate decarboxylase (GAD) produces GABA in mitochondria by irreversibly decarboxylating L-glutamate in the presence of pyridoxal-5′-phosphate coenzyme (Cho et al., 2011). GABA is pervasive and serves a variety of crucial roles. GABA is a crucial component of the spore germination process in the bacteria Bacillus megaterium and Neurospora crassa. The major inhibitory neurotransmitter GABA improves plasma concentr ations of growth hormones and protein synthesis in the brain while inhibiting small airway-derived lung adenocarcinoma, (Choi et al., 2006). GABA acts as a major inhibitory neurotransmitter that sends chemical messages in the mammalian central nervous system. It plays a role in a variety of physiological processes, including reducing anxiety and menopausal symptoms, regulating blood pressure, enhancing visual cortical function and preventing diabetes, (Hagiwara et al., 2004). It also helps with insomnia, depression and stress relief. In addition to its calming and diuretic properties, -aminobutyric acid may have positive effects on the body’s immunological system, hypertension, diabetes, depression and hypertension, (2013) Yuan et al. It is possible to chemically or biologically synthesize GABA, (2003) (Inoue et al.). Finding a natural way to manufacture and enhance GABA in food is essential, because adding chemical GABA directly to food is seen as unnatural and dangerous because it can result in disorde rs including diabetes, heart disease and cancer. Most GABA is produced through the fermentation of microbes such as yeast, fungus and bacteria, (2012) (Dhakal et al.). The lactic acid bacteria (LAB), which include Lactobacillus buchneri are one of the microorganisms that are employed to manufacture GABA.
2. PHARMACEUTICAL PROPERTIES OF GABA
2.1 Neurological disorder prevention
Neurological disorders cause physical or psychological symptoms when a portion of the nervous system or brain is dysfunctional. According to Parvez et al. (2018), it encompasses epilepsy, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, cerebrovascular disorders, neuro-infections and sleeplessness. There is proof that GABA can enhance memory and brain functions while reducing neurodegeneration. (Table 1)
2.2 Anti-diabetic effect
Diabetes is an endocrine condition that results in persistent hyperglycemia, due to impaired insulin secretion or activity and altered glucose metabolism, Kharroubi et al. (2015). Notably, studies have demonstrated the effectiveness of GABA and GABA-enriched natural products in reducing blood sugar, reducing insulin resistance, promoting insulin release and preventing pancreatic damage. (Table 1)
2.3 Antioxidant effect
The unpaired electrons in the free radicals are produced by living things and from external sources. According to Phaniendra et al. (2015), a high amount of free radicals may harm the tissues and cells of the body, speeding up human ageing and contributing to a number of disorders. Therefore, consuming natural products with a strong antioxidant effect is beneficial for preventing diseases brought on by free radicals.
2.4 Anti-cancer effect
According to Ribas et al. (2016), cancer contributes to apoptosis suppression, invasion and metastasis of cells. Surgery, radiation therapy and chemotherapy are the main components of today’s cancer treatments. These methods are frequently used to treat all types of tumours but may come with a number of drawbacks. GABA’s ability to induce apoptosis and decrease proliferation and metastasis has made it a promising drug for controlling cancer. (Table 1)
Table 3.1 – Effects of GABA
3. Factors affecting GABA synthesis
The pace at which GABA is produced by microorganisms is influenced by several fermentation parameters and the ideal conditions for each type of fermenting bacterium depend on the characteristics of the GADs. To maximize GABA synthesis, it will be necessary to characterize the biochemical characteristics of the GADs in the relevant bacteria. Temperature, pH, fermentation duration, glutamate concentration and culture media additions are the most prevalent and important variables. (Dhakal et. al., 2012)
3.1 Effect of temperature
The maximum GABA yield via fermentation is significantly influenced by the effect of incubation temperature. The thermodynamic equilibrium of a reaction, biocatalyst and other processes are all impacted by temperature. Both a high cell density and the proper culture temperature are required for the highly effective conversion of glutamate to GABA, (2009) (Kim et al.). Growth of Lb. brevis NCL912 rose with rising temperature and peaked at 35°C before declining as the temperature climbed. At temperatures between 30°C and 35°C, cultured Lb. plantarum DSM19463 produced the most GABA (59 M/h) (Cagno et al., 2010). Generally, a high GABA output was achieved within the ranges of 25 to 40°C for fermenting. (Dhakal et. al., 2012)
3.2 Effect of pH
According to Komatsuzaki et al. (2005), the pH of a fermentation process often has the most significant impact on the production of GABA in microorganisms. Because different microorganisms’ biochemical properties of GAD differ, the optimal pH level for the maximum production of GABA depends on the species, (2008) (Yang et al.). According to Cagno et al. (2010), Lb. plantarum DSM19463 produced the most GABA (59 M/h) at pH 6.0, while Lb. paracasei NFRI 7415 produced the most GABA (210 mM) at pH 5.0. (2000) Kumar et al. The initial pH of the fermentation medium affects the final GABA yield, because the pH of the medium fluctuates over time during fermentation; Consequently, the pH of the medium should be timely changed to maintain the ideal pH. (Lu et. al., 2009, Kim et. al.,2009, I et.al.,2010)
3.3 Effect of the fermentation time
Lb. Paracasei NFRI 7415 and Lb. plantarum DSM19463 took 144 h and 72 h of fermentation to produce the greatest production of GABA at 60 mM and 4.83 mM, respectively. Time plays a significant effect in the fermentation and the production of GABA. (Cagno et. al., 2010).
3.4 Effect of media additives
GABA generation by microbial fermentation is influenced by nutrient content and growth conditions, (2003) Wang et al. Additionally, media supplements like glutamate and PLP, which are coenzymes of GAD, have a significant impact on the production of GABA during fermentation (Yang et al., 2008). The production of Gamma Amino Butyric Acid (GABA) can be influenced by a number of factors, including carbon and nitrogen supplies.
4. GABA producing microorganisms and their isolation sources
Gamma Amino Butyric Acid (GABA) can be produced by a variety of bacteria and fungi in microorganisms. GABA is a compound that is present in numerous moulds, fungus and yeast in addition to bacteria. (Dhakal et. al.,2012)
4.1 BACTERIA
Because of their diverse production traits and probiotic benefits in bacteria, LAB is crucial for GABA-producing microorganisms, (Yanhua et al., 2020). Numerous strains of Lactobacillus (Lb.) and Lactococcus (Lc.) are included in LAB. Brevis was isolated from a variety of fermented foods, including fresh milk, Chinese traditional paocai, Korean fermented vegetable kimchi, Chinese traditional kimchi and black raspberry juice, (Huang et al., 2007).
Numerous studies have demonstrated that Lb. Brevis can produce a high yield of GABA, when compared to other LAB species, 2020 (Yanhua et al.). Despite the fact that numerous GABA-producing LAB strains have already been separated and characterized, additional study on the isolation and characterization of the LAB is required, since different types of GABA-producing LAB are crucial for the food sector.
4.2 Yeast
Gamma Amino Butyric Acid (GABA) was first extracted from acid-treated yeast extracts in GABA-producing dbacteria. Later, it was shown to be present in untreated yeast in the free state to the extent of 1 to 2% by dry weight (Reed, 1950). While analysing the amino acid profile of red yeast, Rhodotorula glutinis, GABA was once more found. (Krishnaswamy & Giri,1953).
4.3 Moulds
Moulds are multicellular filamentous fungi, including the GABA-containing Aspergillus nidulans and A. niger. An unexpected buildup of GABA was found in A. niger during acidogenesis (Kubicek et al., 1979). A mould called Aspergillus oryzae is used to ferment rice-koji for sake brewing.
5. Conclusion
Reviewing the GABA synthesis from diverse fermented food sources was the goal of this study. GABA can be manufactured chemically in a number of ways, but when it comes from eco-friendly and secure microorganisms, it is thought to be safe for consumption. Lactic acid bacteria (LAB) are one of the microorganisms that create GABA and are frequently found in many fermented foods. Nevertheless, other microorganisms are also employed, such as algae, yeast and moulds. The kind of species employed to produce GABA will determine how much of it is produced. GABA thus has the potential to provide people with a range of health advantages thanks to recent developments.
References:
1. H. Aoki, I. Uda, K. Tagami, Y. Furuya, Y. Endo (2003), “The production of a new tempeh-like fermented soybean containing a high level of γ -aminobutyric acid by anaerobic incubation with Rhizopus the production of a new tempeh –like fermented soybean containing a high level of g -aminobutyric acid by anaerobik, Biosci. Biotechnol”. Biochem. 67 (5) (2003) 1018–1023.
2. Di Cagno, R.; Mazzacane, F.; Rizzello, C.G.; Angelis, M.D.E.; Giuliani, G.; Meloni, M.; Servi, B.D.E.; Marco, G. (2010), “Synthesis of γaminobutyric acid (GABA) by Lactobacillus plantarum DSM19463: functional grape must beverage and dermatological applications” Appl. Microbiol. Biotechnol. 86, 731–741
3. Cho SY, Park MJ, Kim KM, Ryu JH, Park HJ (2011), “Production of high γ-aminobutyric acid (GABA) sour kimchi using lactic acid bacteria isolated from mukeunjee kimchi. Food Sci Biotechnol” 20 (2): 403-408. doi:10.1007/s10068-011-0057-y.
4. Choi, S.I.; Lee, J.W.; Park, S.M.; Lee, M.Y.; Ge J.I.; Park, M.S.; Heo, T.R. (2006), “Improvement of gamma-aminobutyric acid (GABA) production using cell entrapment of Lactobacillus brevis GABA 057” J. Microbiol. Biotechnol. 16, 562–568.
5. Dhakal R, Bajpai VK, Baek KH (2012), “Production of GABA (γ – aminobutyric acid) by microorganisms: a review” Braz J Microbiol 43:1230–1241
6. Florey E. GABA, (1991) “History and perspectives of GABA from Fruits” J Physiol Pharma, 69 (7): 1049-1056 doi:10.1139/y91-156
7. Hagiwara, H., T. Seki, and T. Ariga (2004), “The effect of pre-germinated brown rice intake on blood glucose and PAI-1 levels in streptozotocin-induced diabetic rats” Biosci. Biotechnol. Biochem. 68:444–447.
8. Huang, J.; Mei, L.; Sheng, Q.; Yao, S.; Lin, D. (2007), “Purification and characterization of glutamate decarboxylase of lactobacillus brevis CGMCC 1306 isolated from fresh milk” Chinese J. Chem. Eng. 15, 157- 161.
9. Huang, J.; Mei, L.; Wu, H.; Lin, D. (2007), “Biosynthesis of caminobutyric acid (GABA) using immobilized whole cells of Lactobacillus brevis” World J. Microbiol. Biotechnol. 23, 865–871.
10. Komatsuzaki, N., J. Shima, S. Kawamoto, H. Momose, and T. Kimura (2005.), “Production of γ-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods” Food Microbiol. 22:497–504
11. Krishnaswamy, P. R.; Giri, K. V. (1953), “The occurrence of 4-aminobutyric acid and glutamic acid decarboxylase in red yeast (Rhodotorula glutinis)” Curr. Sci. 22, 143-144.
12. Kubicek, C. P.; Hampel W.; Rohr M. (1979), “Manganese deficiency leads to elevated amino acid pools in critic acid accumulating Aspergillus niger.” Arch. Microbiol. 123, 73-79
13. Olsen, R.W.; Betz, H. (2006), “GABA and glycine. In Basic Neurochemistry, 7th ed.; Siegel, G.J., Albers, R.W., Brady, S.T., Price, D.L., Eds.; Elsevier Academic Press: Boston, MA, USA, 2006.
14. Reed, L. J. (1950), “The occurrence of c-aminobutyric acid in yeast extract; its isolation and identification” J. Biol. Chem. 183, 451-458
15. Siragusa, S., M. De Angelis, R. Di Cagno, C. G. Rizzello, R. Coda, and M. Gobbetti. (2007), “Synthesis of γ-aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses” Appl. Environ. Microbiol. 73:7283–7290.
16. Steward, F.C.; Thompson, J. F.; Dent, C. E. (1949), “γ- aminobutyric acid: a constituent of the potato tuber?” Science 110, 439–440.
17. Wang, J.J.; Lee, C.L.; Pan, T.M. (2003), “Improvement of monacolin K, c-aminobutyric acid and citrinin production ratio as a function of environmental conditions of Monascus purpureus NTU 601” J. Ind. Microbiol. Biotechnol. 30, 669–676
18. Yang, S.Y.; Lu, F.X.; Lu, Z.X.; Bie, X.M.; Jiao, Y.; Sun, L.J.; Yu, B. (2008), “Production of gamma-aminobutyric acid by Streptococcus salivarius subsp thermophilus Y2 under submerged fermentation. Amino Acids 34, 473-478
19. Yanhua Cui , Kai Miao, Siripitakyotin Niyaphorn and Xiaojun Qu, (2020) “Production of Gamma-Aminobutyric Acid from Lactic Acid Bacteria: A Systematic Review” International Journal of Molecular Sciences.
20. C. Yuan, H.V. Lin, G. Jane, (2013), “Gamma-aminobutyric acid production in black soybean milk by Lactobacillus brevis FPA 3709 and the antidepressant effect of the fermented product on a forced swimming rat model” Process Biochem. 48 (4) 559–568.
About the Authors:
Dr. Anuradha Mishra & Dr. Sukriti Singh
Department of Food Science & Technology,
M.M.I.C.T. & B.M., M.M. (Deemed to be University),
Mullana, Ambala, Haryana, India.
Email ID: anu25.memo@gmail.com
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