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MOLECULES · 2025 ·Vol. 30 ·期 4 ·897 · IF 4.6

Development and Techno-Economic Evaluation of Crystallization Techniques for GABA Purification from Fermentation Broth

Yu Jing,Jinxu Zhang,Shengping You,Mengfan Wang,Rongxin Su,Wei Qi

γ-aminobutyric acid, a critical neurotransmitter, is experiencing an increasing demand in the medical and health fields. Conventional processes for γ-aminobutyric acid purification from fermentation broth encounter significant challenges, such as high ethanol usage, low yield, complex process flow, and environmental pollution. Therefore, a purification process based on crystallization techniques was developed to address the above issues. The process was implemented in two stages: desalination and γ-aminobutyric acid treatment. Na 2 SO 4 was effectively removed through a cooling crystallization technique. γ-aminobutyric acid with a purity of 98.66% and a yield of 67.32% was further obtained through a designed “antisolvent-cooling” crystallization process in a 3.2 L system. Moreover, the new process reduced ethanol usage compared to conventional processes, streamlined the purification process flow, and was more environmentally sustainable. Furthermore, we established an industrial-scale model for γ-aminobutyric acid production. Techno-economic analysis indicates that an investment in a plant with an annual capacity of 74.16 tons of γ-aminobutyric acid is projected to achieve payback in 1.98 years. In conclusion, the crystallization-based purification process is poised for industrial-scale γ-aminobutyric acid production due to its high efficiency, economic viability, energy conservation, and environmental compatibility.

研究领域: 生物工程 · 化学工程 · 制药工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2026 · IF 10.4

Multispectral and molecular dynamics investigation of GABA-induced gelation behavior in walnut protein isolate

Wen Tan,Songwen Xue,Wenjie Xie,Changqing Wei,Jinhu Tian

GABA enhances WPI gelation via protein unfolding and hydrophobic region exposure. • Hydrogen bonding and hydrophobic interactions promote formation of a dense gel network. • Molecular dynamics simulations identify glutelin as the major responsive walnut protein fraction. Walnut protein isolate (WPI) is a high-quality plant protein source. However, its application in gel-based foods is limited by weak gelling properties. The present study elucidated the molecular mechanisms by which γ-aminobutyric acid (GABA) enhanced the gelation of WPI. The addition of GABA (0.80%) significantly increased the water holding capacity of WPI gels (from 61.9% to 85.2%) and improved the textural properties, including hardness and springiness. Mechanistically, GABA induced protein unfolding (transitioning α-helix to ordered β -sheets), exposing buried hydrophobic groups. This facilitated a dense, fine-stranded network stabilized by enhanced hydrogen bonding and hydrophobic interactions. Molecular dynamics simulations revealed that GABA triggered global structural rearrangement in walnut glutelin, while inducing local conformational activation in 11S globulin. Notably, the GABA-glutelin complex maintained high stability via hydrogen bonds and van der Waals forces, serving as the primary driver for enhanced mechanical strength. This study clarified how GABA regulated the gelation behavior of WPI through protein conformational rearrangement and enhanced intermolecular interactions, providing a theoretical basis for improving the application of walnut protein in structured plant-based foods. Download: Download high-res image (176KB) Download: Download full-size image

✓ 已验证 DOI PubMed 高影响因子
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Pharmacognosy Magazine · 2017 · IF 1.069

Anti-epileptic Effects of Valepotriate Isolated from Valeriana jatamansi Jones and Its Possible Mechanisms

An Wu,Xia Ye,Qiang Huang,Wei-Min Dai,Jian-Min Zhang

Objective: This work aimed to investigate the anti-epileptic effects of valepotriate isolated from Valeriana jatamansi Jones and studied its possible mechanisms. Methods: The anti-epileptic effects of valepotriate were studied using maximal electroshock-induced seizure (MES), pentylenetetrazole (PTZ)-induced epilepsy, and pentobarbital sodium-induced sleeping model in mice. The possible anti-epileptic mechanisms of valepotriate were investigated by analyzing the expressions of GABA A , GABA B , glutamic acid decarboxylase (GAD65), Bcl-2, and caspase-3 in the brain using Western blot assay. Results: The results indicated that valepotriate showed significant anti-epileptic activity against MES- and PTZ-induced epilepsy at doses of 5, 10, and 20 mg/kg, and ED 50 values for MES- and PTZ-induced epilepsy were 7.84 and 7.19 mg/kg, respectively. Furthermore, valepotriate (10 and 20 mg/kg) can significantly prolong sleeping time and shorten the latency time on the pentobarbital sodium-induced sleeping time test. Furthermore, valepotriate (5, 10, and 20 mg/kg) could significantly up-regulate the expression of GABA A , GAD65, and Bcl-2 and down-regulate the expression of caspase-3, but had no significant effect on the expression of GABA B . Conclusion: The results indicated that valepotriate had anti-epileptic activity and the mechanisms might be associated with regulation of GABA and inhibition of neuronal apoptosis. SUMMARY Anti-epileptic effect of valepotriate was investigated for the 1 st time Valepotriate showed notable anti-epileptic activity Valepotriate can significantly increase the expression of GABA A , glutamic acid decarboxylase 65, and Bcl-2 and reduce the expression of caspase-3. Open in a separate window

CAS / MDL: 630-93-3 92-84-2
研究领域: 药理学 · 神经科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2018 ·Vol. 23 ·期 3 ·554 · IF 3.098

Quantitative 1H-NMR Spectroscopy for Profiling Primary Metabolites in Mulberry Leaves

Qianqian Liang,Qiuying Wang,Yuan Wang,Ya-nan Wang,Jia Hao,Miaomiao Jiang

The primary metabolites in aqueous extract of mulberry (Morus albaL.) leaves were characterized by using proton nuclear magnetic resonance (1H-NMR) spectroscopy. With the convenience of resonance assignment, GABA together with the other 10 primary metabolites was simultaneously identified and quantified in one1H-NMR spectrum. In this study, external calibration curves for metabolites were employed to calculate the concentrations of interests. The proposed quantitative approach was demonstrated with good linearity (r2ranged in the interval of 0.9965–0.9999), precision, repeatability, stability (RSD values in the ranges of 0.35–4.89%, 0.77–7.13% and 0.28–2.33%, respectively) and accuracy (recovery rates from 89.2% to 118.5%). The established1H-NMR method was then successfully applied to quantify 11 primary metabolites in mulberry leaves from different geographical regions within a rapid analysis time and a simple sample preparation procedure.Keywords:quantitative1H-NMR;Morus alba;amino acids;saccharides;organic acids

CAS / MDL: 57-50-1
研究领域: 分析化学 · 植物科学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Science · 2024 · IF 14.3

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

Jiawan Wang,Hao Zhang,Hailong Yuan,Siqi Chen,Ying Yu,Xuan Zhang,Zeyu Gao,Heng Du,Weitao Li,Yaohui Wang,Pengyan Xia,Jun Wang,Moshi Song

The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri ( L. reuteri ) is a well-studied probiotic that can colonize mammals including humans with known cholesterol-lowering properties and anti-inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ-aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS-stimulated bone marrow-derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage-mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.

CAS / MDL: 96949-21-2
研究领域: 心血管疾病 · 微生物组 · 炎症 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Processes · 2026 ·Vol. 14 ·期 9 ·1347 · IF 3.4

CRISPR-Cas9 Mediated UGA1 Knockout in Saccharomyces cerevisiae for Enhanced GABA Production in Wort Beverage

Zhuoling Ding,Kadireya Tuerxun,Xueqing Luo,Shishui Zhou

γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter, is known for its physiological functions in alleviating anxiety and improving sleep. Currently, high-yielding GABA food products are mainly obtained through screening wild-type high-producing strains (e.g.,Saccharomyces cerevisiaeisolated from Sichuan pickles yielding 0.67 g/L) or employing co-culture systems (e.g.,Enterococcus faeciumandLactiplantibacillus plantarumreaching 6.35 g/L). While effective, these methods often rely on natural screening strains or multi-microbial interactions. This study employed CRISPR-Cas9 technology to knockout theUGA1gene inSaccharomyces cerevisiae, a key gene responsible for GABA degradation. Starting from the low higher alcoholSaccharomyces cerevisiaeSY-LH, we successfully constructed the recombinant strain SY-LHU. Remarkably, this study discovered a significant upregulation ofGAD1gene expression followingUGA1knockout, which further enhanced GABA synthesis capacity. Under optimal fermentation conditions (inoculum size 4 × 107cells/mL, wort concentration 10 °P, sugar addition 60 g/L, 30 °C for 10 days, and mixing the malt broth every 48 h), the validation fermentation was performed and the GABA content in the wort beverage reached 280.36 mg/L, representing a 385.4% increase compared to the pre-optimization level. Furthermore, sensory evaluation by a trained panel yielded a mean score of 88, with no significant off-flavors detected, demonstrating the product’s high consumer acceptance. This pioneering work provides a novel and feasible technical pathway for developing functional alcoholic beverages with sleep-aiding properties.

✓ 已验证 DOI 高影响因子
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MOLECULES · 2026 ·Vol. 31 ·期 11 ·1847 · IF 5.1

Effects of Exogenous Selenium on Accumulations of Selenium, GABA and Antioxidant Activity of Chestnut During Germination

Haifen Wang,Weiwei Liu,Fei Peng,Ziye Zhang,Jiawei Cao,Jiayu Shi,Liang He,Yunbin Jiang,Mengshi Wang,Junwei Yuan

The objective of this study was to investigate the effect of exogenous selenium on selenium enrichment and antioxidant activity of germinated chestnuts. We treated ‘Zaofeng’ chestnuts with Na2SeO3at concentration of 0, 20, 40, 60 and 80 mg/L, and analyzed, during germination, the level of total Se, SeCys2, MeSecys, SeIV, SeMet, SeVI, γ-aminobutyric acid (GABA), antioxidant enzyme (phenylalanine ammonialyase (PAL), glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)) activity, non-enzymatic antioxidant substances (total polyphenols and flavonoids) content and antioxidant capacity (DPPH, ABTS). The results indicated that low concentrations of selenium (20–40 mg/L) significantly promoted the organic transformation of selenium, with a Se-enrichment rate over 74%. Antioxidant enzyme (PAL, SOD, CAT) activities and total phenol content were enhanced by 1.1 to 1.9-fold compared with the control, leading to a 12.2–29.2% improvement in antioxidant capacity (DPPH and ABTS). In contrast, the high concentration of selenium (80 mg/L) induced oxidative stress, inhibiting enzyme (PAL, SOD, CAT) activities (reduced by 14.1–20.5%) and decreasing antioxidant capacity (DPPH) by approximately 19.0%. During chestnut germination, selenite was absorbed by the embryo and subsequently transformed into organic Se in vivo, ultimately being stored mainly as SeCys2. The selenium enrichment rate decreased significantly with increasing Na2SeO3treatment concentration: from 86.4% at 20 mg/L to 62.2% at 80 mg/L. Furthermore, treatment with 40 mg/L Na2SeO3led to a significant increase in GABA content of germinated chestnuts, reaching 1.3 times that of the control group. Overall, germination with 20–40 mg/L Na2SeO3is an effective condition for producing Se-enriched chestnut sprouts with enhanced GABA and antioxidant capacity, offering a potential functional food ingredient.

✓ 已验证 DOI PubMed 高影响因子
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Metabolites · 2023 ·Vol. 13 ·期 2 ·283 · IF 4.1

Sensitivity Intensified Ninhydrin-Based Chromogenic System by Ethanol-Ethyl Acetate: Application to Relative Quantitation of GABA

Haixing Li,Lingqin Wang,Lijuan Nie,Xiaohua Liu,Jinheng Fu

Gamma-aminobutyric acid (GABA) is a functional metabolite in various organisms. Herein, a sensitivity intensified ninhydrin-based chromogenic system (SINICS), achieved by ethanol and ethyl acetate, is described for the reliable relative quantitation of GABA. A 2.9 mL SINICS kit comprises 1% ninhydrin, 40% ethanol, 25% ethyl acetate, and 35 μL 0.2 M sodium acetate buffer (pH 5.0). In practice, following the addition of a 0.1 mL sample to the kit, the chromogenic reaction is completed by heating at 70 °C for 30 min. The kit increased the color development sensitivity of L-glutamic acid and GABA, with the detection limits being reduced from 20 mM and 200 mM to 5 mM and 20 mM, respectively. The chromophore was stable for at least 2 h at room temperature, which was sufficient for a routine colorimetric analysis. The absorbance at 570 nm with the deduction of background directly represents the content of amino acid. For a proof-of-concept, the SINICS was adopted to optimize the GABA fermentation process ofLevilactobacillus brevisCD0817. The results demonstrated that SINICS is an attractive alternative to the available ninhydrin-based colorimetric methods.Keywords:ninhydrin-based chromogenic system;colorimetry analysis;relative quantitation;gamma-aminobutyric acid;amino acids

研究领域: 生物化学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2025 · IF 9.8

Regulation of peptide hydrophobicity by self-assembly of casein peptides with ferulic acid to potentially reduce peptide bitterness and improve in vitro digestive activity

Si-Yi Han,Hong-Fu Zhao,Bo-Kang Yu,Ying-Hua Zhang,Zhi-Shen Mu

The main purpose of this study was to investigate the structural properties, mechanism of action, bitter taste changes, and γ-aminobutyric acid transaminase (GABA-T) inhibitory activity of CH-FA complexes in vitro digestion by self-assembly of casein hydrolysate (CH) and ferulic acid (FA). Structural analysis revealed that CH-FA was formed spontaneously, driven primarily by hydrophobic interactions and hydrogen bonding. The electron tongue results demonstrated that the bitter value of CH was reduced by 30.89 %, which may be due to the improvement of the hydrophobic amino acid microenvironment and the reduction of binding to the bitter receptor, thereby reducing the bitterness. In vitro digestion stage, the protein digestibility of CH was inhibited by FA, which increased the GABA-T inhibitory activity of CH by 13.96 % at the end of digestion. The present study elucidated the self-assembly mechanism of CH with FA and improved the value of casein peptides in the food industry.

CAS / MDL: 60-24-2
研究领域: 食品科学 · 生物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2026 · IF 6.7

Structural Modifications Redirect Phenylpyrazole Ectoparasiticides from the Ion Channel Pore to an Allosteric Site on GABA Receptors

Tianhao Zhou,Zihan Cheng,Honglei Xie,Ailing Liu,Shoujun Li,Xiaomu Qiao,Jia Huang

Abstract Phenylpyrazole ectoparasiticides, exemplified by fipronil, act as noncompetitive antagonists of arthropod GABA receptors by blocking the ion channel pore. Here, we investigated the molecular mechanism of the newer phenylpyrazole nicofluprole using Drosophila melanogaster. CRISPR/Cas9-mediated mutagenesis and pharmacological assays showed that A301 substitutions in the pore-forming TM2 helix conferred strong resistance to fipronil but had little effect on nicofluprole sensitivity. In contrast, G335 mutations in TM3 markedly reduced nicofluprole activity. Molecular docking supported these findings, indicating that nicofluprole binds at the transmembrane subunit interface rather than within the central pore, consistent with allosteric modulation. These results demonstrate that structural modification of the phenylpyrazole scaffold can redirect target-site engagement from the pore to an allosteric site, explaining the lack of cross-resistance with traditional pore blockers and expanding strategies for GABA receptor-targeted insecticide design.

✓ 已验证 DOI 高影响因子
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JOURNAL OF FOOD PROCESSING AND PRESERVATION · 2016 ·Vol. 41 ·期 5 ·e13126 · IF 0.894

A Systematic Assesment on Vitamins (B2, B12) and GABA Profiles in Fermented Soy Products Marketed in China

L. Xu,W.X. Cai,B.J. Xu

This study aimed to provide comprehensive health beneficial profiles of fermented soy products and further provide reference values of vitamin B 2 and B 12 and GABA enrichment products. High performance liquid chromatography (HPLC) analyses were applied to systemically investigate the vitamins and GABA. The highest vitamin B 2 content of 6.06 μg g −1 was detected in “Wangzhihe” sufu. All natto samples showed relatively higher vitamin B 2 content with an average value of 3.35 μg g −1 compared to the other fermented soy products. “Liubiju” dry yellow soybean paste was detected with the highest vitamin B 12 content of 732.94 ng g −1 . All sufu samples presented relatively higher GABA levels with an average value of 11.58 mg g −1 . Fermented soy products could be used as supplements of vitamins and bioactive substances such as GABA. It can be concluded that fermentation can be used as an alternative method to chemical synthesis of vitamin B 12 and GABA. Practical Applications Presented information will guide consumers to choose fermented soy product to gain health benefit components, especially for vegetarian to find food sources of vitamin B 12 . The study will help food manufacturers to understand secondary metabolites production through fermentation. Current results make food industry commercially feasible to produce special amino acids (such as GABA) and vitamins B 2 and B 12 .

研究领域: 食品科学 · 营养学 · 生物化学
✓ 已验证 DOI 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 2 ·1051 · IF 4.9

Cellulase Promotes Mycobacterial Biofilm Dispersal in Response to a Decrease in the Bacterial Metabolite Gamma-Aminobutyric Acid

Jiaqi Zhang,Yingying Liu,Junxing Hu,Guangxian Leng,Xining Liu,Zailin Cui,Wenzhen Wang,Yufang Ma,Shanshan Sha

Biofilm dispersal contributes to bacterial spread and disease transmission. However, its exact mechanism, especially that in the pathogenMycobacterium tuberculosis, is unclear. In this study, the cellulase activity of theM. tuberculosisRv0062 protein was characterized, and its effect on mycobacterial biofilm dispersal was analyzed by observation of the structure and components of Rv0062-treated biofilm in vitro. Meanwhile, the metabolite factors that induced cellulase-related biofilm dispersal were also explored with metabolome analysis and further validations. The results showed that Rv0062 protein had a cellulase activity with a similar optimum pH (6.0) and lower optimum temperature (30 °C) compared to the cellulases from other bacteria. It promoted mycobacterial biofilm dispersal by hydrolyzing cellulose, the main component of extracellular polymeric substrates of mycobacterial biofilm. A metabolome analysis revealed that 107 metabolites were significantly altered at different stages ofM. smegmatisbiofilm development. Among them, a decrease in gamma-aminobutyric acid (GABA) promoted cellulase-related biofilm dispersal, and this effect was realized with the down-regulation of the bacterial signal molecule c-di-GMP. All these findings suggested that cellulase promotes mycobacterial biofilm dispersal and that this process is closely associated with biofilm metabolite alterations.Keywords:biofilm;biofilm dispersal;Mycobacterium tuberculosis;cellulase;GABA;c-di-GMP

研究领域: 微生物学 · 生物化学 · 传染病
✓ 已验证 DOI PubMed 高影响因子
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