Strategies for improvement of gamma-aminobutyric acid (GABA) biosynthesis <i>via</i> lactic acid bacteria (LAB) fermentation

Pannerchelvan, Sangkaran; Rios‐Solis, Leonardo; Wong, Fadzlie Wong Faizal; Zaidan, Uswatun Hasanah; Wasoh, Helme; Mohamed, Mona H.; Tan, Joo Shun; Mohamad, Rosfarizan; Halim, Murni

doi:10.1039/d2fo03936b

Cited by 29 publications

(21 citation statements)

References 163 publications

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“…Hence, the direct input of glucose, alkanes, and other substrates for fermentation under nonsterile conditions may still lead to the production of a small amount of DCA. By combining the construction and transformation of strains with the simplification of the fermentation process, the difficulty of production control can be reduced and the stability of fermentation can be improved, thereby enabling cost reduction …”

Section: Prospecting the Synthesis Of Dicarboxylic Acids From The Per...mentioning

confidence: 99%

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Mid–Long Chain Dicarboxylic Acid Production via Systems Metabolic Engineering: Progress and Prospects

Gu,

Zhu,

Zhang

et al. 2024

J. Agric. Food Chem.

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Mid-to-long-chain dicarboxylic acids (DCA i , i ≥ 6) are organic compounds in which two carboxylic acid functional groups are present at the terminal position of the carbon chain. These acids find important applications as structural components and intermediates across various industrial sectors, including organic compound synthesis, food production, pharmaceutical development, and agricultural manufacturing. However, conventional petroleum-based DCA production methods cause environmental pollution, making sustainable development challenging. Hence, the demand for eco-friendly processes and renewable raw materials for DCA production is rising. Owing to advances in systems metabolic engineering, new tools from systems biology, synthetic biology, and evolutionary engineering can now be used for the sustainable production of energy-dense biofuels. Here, we explore systems metabolic engineering strategies for DCA synthesis in various chassis via the conversion of different raw materials into mid-to-long-chain DCAs. Subsequently, we discuss the future challenges in this field and propose synthetic biology approaches for the efficient production and successful commercialization of these acids.

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Section: Prospecting the Synthesis Of Dicarboxylic Acids From The Per...mentioning

confidence: 99%

“…By combining the construction and transformation of strains with the simplification of the fermentation process, the difficulty of production control can be reduced and the stability of fermentation can be improved, thereby enabling cost reduction. 158 4.2.2. Optimization and Scale-up of the Fermentation Process.…”

Section: 11mentioning

confidence: 99%

Mid–Long Chain Dicarboxylic Acid Production via Systems Metabolic Engineering: Progress and Prospects

Gu,

Zhu,

Zhang

et al. 2024

J. Agric. Food Chem.

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“…Lactic acid bacteria, such as GRAS (generally considered to be safe) strains, are often used as starters for functional food fermentation and in pharmaceutical fields. Therefore, lactic acid bacteria that produce GABA efficiently are the main focus of GABA-producing bacteria at present [11][12][13][14][15]. The lactic acid bacteria with GABA synthesis identified thus far mainly include Lactobacillus (L.) brevis, L. buchneri, Streptococcus thermophilus, L. paracasei, Lactococcus lactis, and L. plantarum [11,14,[16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Silkworm Pupae Coupled with Glucose Control pH Mediates GABA Hyperproduction by Lactobacillus hilgardii

Gong

et al. 2023

Fermentation

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γ-Aminobutyric acid (GABA) is a ubiquitous nonprotein amino acid that has multiple physiological functions and has received significant attention in the pharmaceutical and food industries. Although there are many GABA-producing bacteria, the high cost of strain cultivation limits its food additive and pharmaceutical raw material application. In our study, Lactobacillus hilgardii GZ2, a novel GABA-producing strain, was investigated. We attempted to replace nitrogen sources with silkworm pupae, the waste resource of the silk reeling industry, in GYP complex medium. The GABA titer reached 33.2 g/L by using 10 g/L silkworm pupae meal instead of tryptone. Meanwhile, the pH of fermentation was automatically controlled by adjusting the addition of glucose and monosodium glutamate. Finally, the highest GABA yield and productivity were 229.3 g/L and 3.2 g/L/h in L. hilgardii when silkworm pupae meal was replaced with tryptone combined with glucose and monosodium glutamate feeding. By utilizing the waste resource to reduce the cost of the nitrogen source and automatically controlling the pH in L. hilgardii, a hyper titer and productivity of GABA was generated for applications in the food and pharmaceutical industries.

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“…Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, has been reported to have hypotensive, diuretic, and sedative effects [1]. GABA is extensively dispersed in animals, plants, and microorganisms, and its benefits for human health are highly regarded [2]. In the field of food additives, Gabaron tea (>150 mg GABA/100 g), a GABA-enriched tea beverage with the ability to decrease blood pressure, was created by Japanese scientists in the 1980s and attracted widespread attention in the market [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Lactobacillus brevis CRL 2013 was isolated from quinoa and could produce 265 mM GABA with a molar yield of over 99% from modified MRS broth with MSG [22]. A two-stage pH-control strategy was widely applied to GABA fermentation, the parameters of which could be adjusted for bacterial growth or GABA synthesis separately [2]. The glutamate-decarboxylase system was reconstructed in Lactococcus lactis and 33.52 g/L GABA was achieved from MSG under a two-stage pHcontrol strategy [14].…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of Gamma-Aminobutyric Acid by Engineered Clostridium tyrobutyricum Co-Overexpressing Glutamate Decarboxylase and Class I Heat Shock Protein

et al. 2023

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Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system that has a significant beneficial effect on human health. Traditional microbial GABA synthesis requires continuous oxygen supplementation. Here, a new anaerobic platform for GABA production was established with engineered C. tyrobutyricum ATCC 25755, which is considered an ideal anaerobic microbial-cell factory for bioproduction. Glutamate decarboxylase (GAD) and Class I heat-shock proteins were screened and overexpressed, generating an excellent Ct-pMAG strain for monosodium-glutamate (MSG) tolerance and GABA production, with a GABA titer of 14.26 g/L in serum bottles with the mixed substrate of glucose and MSG. Fed-batch fermentation was carried out in a 5 L bioreactor, achieving 35.57 g/L and 122.34 g/L final titers of GABA by applying the pH-free strategy and the pH-control strategy, respectively using MSG. Finally, a two-stage strategy (growth stage and bioconversion stage) was applied using glutamate acid (L-Glu) and glucose as the substrate, obtaining a 400.32 g/L final titer of GABA with a productivity of 36.39 g/L/h. Overall, this study provides an anaerobic-fermentation platform for high-level bio-GABA production.

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Strategies for improvement of gamma-aminobutyric acid (GABA) biosynthesis via lactic acid bacteria (LAB) fermentation

Abstract: Gamma-aminobutyric acid (GABA) is a non-protein amino acid widely distributed in nature and extensively explored for its numerous physiological functions and effects on metabolic disorders. Lactic acid bacteria (LAB) are...

Cited by 29 publications

References 163 publications

Mid–Long Chain Dicarboxylic Acid Production via Systems Metabolic Engineering: Progress and Prospects

Mid–Long Chain Dicarboxylic Acid Production via Systems Metabolic Engineering: Progress and Prospects

Silkworm Pupae Coupled with Glucose Control pH Mediates GABA Hyperproduction by Lactobacillus hilgardii

Biosynthesis of Gamma-Aminobutyric Acid by Engineered Clostridium tyrobutyricum Co-Overexpressing Glutamate Decarboxylase and Class I Heat Shock Protein

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