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Improve gamma‑aminobutyric acid production in Corynebacterium glutamicum by optimizing the metabolic fux

Systems Microbiology and Biomanufacturing 2022年第2期2卷 305-316页

作者： Chengzhen Yao Yuantao Liu Xiaoqing Hu Xiaoyuan Wang State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China International Joint Laboratory on Food Safety Jiangnan UniversityWuxiJiangsuChina Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxiChina Hulunbeier Northeast Fufeng Biotechnology Co.Ltd. HulunbeierChina

gamma-aminobutyric acid is an important nonprotein amino acid and has been extensively applied in pharmaceuticals,livestock,food additives,and so *** is important to develop Corynebacterium glutamicum strains that can efciently produce gamma-aminobutyric acid from *** this study,production of gamma-aminobutyric acid in *** CGY700 was improved by construction of CO_(2) anaplerotic reaction and overexpression of citrate *** co-expression of ppc encoding phosphoenolpyruvate carboxylase and gltA encoding citrate synthase was constructed and optimized in the chromosome to compensate carbon loss and conquer metabolic *** expression of ppc and gltA were controlled by promoters P_(tac) and P_(tacM),and the optimal mode of P_(tacM-ppc)-P_(tac)-gltA was ***,the genes pknG encoding serine/threonine protein kinase G and ldh encoding l-lactate dehydrogenase were deleted,and glnA2 encoding glutamine synthase was overexpressed in the *** fnal strain CGY-PG-304 constructed in this study could produce 41.17 g/L gamma-aminobutyric acid in shake fask cultivation and 58.33 g/L gamma-aminobutyric acid via FedBatch fermentation with a yield of 0.30 g/g ***-PG-304 was constructed by genome editing;therefore,it is stable and not necessary to add any antibiotics and inducer during fermentation.

关键词： gamma-aminobutyric acid Metabolic engineering Corynebacterium glutamicum Phosphoenolpyruvate carboxylase Citrate synthase

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Verification of Lactobacillus brevis tolerance to simulated gastric juice and the potential effects of postbiotic gamma-aminobutyric acid in streptozotocin-induced diabetic mice

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Food Science and Human Wellness 2022年第1期11卷 165-176页

作者： Amro Abdelazez Heba Abdelmotaal Smith Etareri Evivie Maha Bikheet Rokayya Sami Hassan Mohamed Xiangchen Meng Key Laboratory of Dairy Science Ministry of EducationCollege of Food SciencesNortheast Agricultural UniversityHarbin 150030China College of Agriculture and Forestry Linyi UniversityLinyi 276005China Department of Dairy Microbiology Animal Production Research InstituteAgriculture Research CentreDokkiGiza 12618Egypt Department ofMicrobiology SoilWaterEnvironmentand Microbiology Research InstituteAgriculture Research CentreGiza 12619Egypt Department of Food Science&Hunan Nutrition Faculty of AgricultureUniversity of BeninBenin City 300001Nigeria Department of Dairy Science Faculty of AgricultureMinia UniversityMinia 61511Egypt Department of Food Science and Nutrition College of SciencesTaif UniversityP.O.11099Taif21944Saudi Arabia Colin Ratledge Center for Microbial Lipids School of Agriculture Engineering and Food ScienceShandong University of TechnologyZibo 255049China Department of Botany and Microbiology Faculty of ScienceAl-Azhar UniversityAssiut 71524Egypt

The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics *** study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in *** amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were *** vivo experiments were conducted in 7 groups of C57BL/6J *** group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were *** indicated *** strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/*** lowest body weight(ContSTZ)was(19.30±0.25)*** on the blood plasma analysis,*** strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in *** recommended,*** should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.

关键词： Diabetes gamma-aminobutyric acid Postbiotics Lactobacillus brevis In vitro C57BL/6J mice

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gamma-aminobutyric acid promotes human hepatocellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor α3 subunit

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World Journal of Gastroenterology 2008年第47期14卷 7175-7182页

作者： Yan Liu Yue-Hui Li Feng-Jie Guo Jia-Jia Wang Rui-Li Sun Jin-Yue Hu Guan-Cheng Li Tumor ImmunobiologyLaboratory of Cancer Research Institute Central SouthUniversity Chan~sha 410078 Hunan Province. China

AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A receptor α3 subunit(GABRA3) and ***:HCC cell line Chang,HepG2,normal liver cell line L-02 and 8 samples of HCC tissues and paired non-cancerous tissues were analyzed with semiquantitative polymerase chain reaction(PCR) for the expression of GABAA ***2 cells were treated with gamma-aminobutyric acid(GABA) at serial concentrations(0,1,10,20,40 and 60 μmol/L),and their proliferating abilities were analyzed with the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay,cell doubling time test,colon formation assay,cell cycle analysis and tumor planted in nude *** interfering RNA was used for knocking down the endogenous GABRA3 in *** abilities of these cells treated with or without GABA were ***:We identified the overexpression of GABRA3 in HCC *** of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell *** determined the in vitro and in vivo effect of GABA in the proliferation of GABRA3-positive cell lines,and found that GABA increased HCC growth in a dose-dependent ***,the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells,but not GABRA3-knockdown HepG2 *** means that GABA stimulates HepG2 cell growth through ***:GABA and GABRA3 play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.

关键词： Hepatocellular carcinoma Proliferation gamma-aminobutyric acid gamma-aminobutyric acid A receptor a3 subunit RNAi

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A Two-stage pH and Temperature Control with Substrate Feeding Strategy for Production of gamma-aminobutyric acid by Lactobacillus brevis CGMCC 1306

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Chinese Journal of Chemical Engineering 2013年第10期21卷 1190-1194页

作者：彭春龙黄俊胡升赵伟睿姚善泾梅乐和 Department of Chemical and Biological Engineering Zhejiang University Hangzhou 310027 China School of Biological and Chemical Engineering Zhejiang University of Science and Technology Hangzhou 310023China School of Biological and Chemical Engineering Ningbo Institute of Technology Zhejiang University Ningbo 315100China

Methods to optimize the production of gamma-aminobutyric acid （GABA） by Lactobacillus brevis CGMCC 1306 were investigated. Results indicated that cell growth was maximal at pH 5.0, while pH 4.5 was pref-erable to GABA formation. The optimal temperature for cell growth （35 °C） was lower than that for GABA forma-tion （40 °C）. In a two-stage pH and temperature control fermentation, cultures were maintained at pH 5.0 and 35 °C for 32 h, then adjusted to pH 4.5 and 40 °C, GABA production increased remarkably and reached 474.79 mmol·L-1 at 72 h, while it was 398.63 mmol·L-1 with one stage pH and temperature control process, in which cultivation con-ditions were constantly controlled at pH 5.0 and 35 °C. In order to avoid the inhibition of cell growth at higher L-monosodium glutamate （L-MSG） concentrations, the two-stage control fermentation with substrate feeding strat-egy was applied to GABA production, with 106.87 mmol （20 g） L-MSG supplemented into the shaking-flask at 32 h and 56 h post-inoculation separately. The GABA concentration reached 526.33 mmol·L-1 at 72 h with the fer-mentation volume increased by 38%. These results will provide primary data to realize large-scale production of GABA by L. brevis CGMCC 1306.

关键词： gamma-aminobutyric acid Lactobacillus brevis CGMCC 1306 two-stage pH and temperature control substrate feeding

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Sodium glutamate and gamma-aminobutyric acid affect iron metabolism in the rat caudate putamen

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Neural Regeneration Research 2010年第21期5卷 1644-1649页

作者： Na Wang Peng Guan Fei Li Yujian Fu Xianglin Duan Yanzhong Chang Institute of Molecular Neurobiology and Neuropharmacology Hebei Normal University Shijiazhuang 050016 Hebei Province China Department of Basic Courses Hebei Medical University Shijiazhuang 050091 Hebei Province China

Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 （DMT1） and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1 （-IRE）] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1 （-IRE） expression was significantly reduced, but hephaestin expressiori was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMTI（-IRE） and decreasing hephaestin expression. In addition, GABA decreased DMT1 （-IRE） expression in the caudate putamen.

关键词： glutamate gamma-aminobutyric acid tyrosine hydroxylase divalent metal transporter 1 non iron response element hephaestin

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Role of dietary gamma-aminobutyric acid in broiler chickens raised under high stocking density

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Animal Nutrition 2020年第3期6卷 293-304页

作者： Su-Been Jeong Yoo Bhin Kim Jeong-Woo Lee Da-Hye Kim Byung-Hern Moon Hong-Hee Chang Yang-Ho Choi Kyung-Woo Lee Department of Animal Science and Technology Konkuk UniversitySeoul05029Republic of korea CellTech Co. Ltd.Chungbuk27622Republic of Korea Department of Animal Science Gyeongsang National Universityjinju52828Republic of Korea

The present study was conducted to evaluate the effects of dietary gamma-aminobutyric acid(GABA)in broiler chickens raised in high stocking density(HSD)on performance and physiological responses.A total of 900 male broiler chicks(Ross 308)at 1 d old were assigned in a 2×2 factorial arrangement to 4 treatments(10 replicates per treatment)with stocking density,7.5 birds/m^2(low stocking density;LSD)or 15 birds/m^2(HSD),and dietary GABA,0 or 100 mg/*** raised in HSD exhibited a decrease in body weight gain in all phases(Pacids depending on stocking density leading to a moderate to significant *** density decreased alpha-1-acid glycoprotein whereas dietary GABA decreased heterophil-to-lymphocyte ratio and corticosterone in blood or serum *** biochemical parameters were altered by stocking density or dietary *** is concluded that dietary GABA alleviated stress indices including corticosterone and heterophilto-lymphocyte ratio,but failed to reverse stocking density-induced growth depression.

关键词： gamma-aminobutyric acid Stocking density Growth performance Stress indicator Broiler chicken

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Evolution of neurotransmitter gamma-aminobutyric acid, glutamate and their receptors

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Zoological Research 2012年第S3期33卷 I0013-I0019页

作者： Zhiheng GOU Xiao WANG Wen WANG CAS-Max Planck Junior Research Group State Key Laboratory of Genetic Resources and EvolutionKunming Institute of Zoologythe Chinese Academy ofSciences(CAS)Kunming 650223China Graduate School of the Chinese Academy of Sciences Beijing 100049China

gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have began to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino acid Transporter （EAAT）, a transport protein, which plays an important role in the GABA-glutamate ＂yin and yang＂ balanced regulation. Finally, based on current advances, we propose several potential directions of future research.

关键词： gamma-aminobutyric acid Glutamate Neurotransmitter Receptor Evolution Yin and yang regulation

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Effects of gamma-aminobutyric acid on Performance of Lactating Sows during Heat Weather

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Animal Husbandry and Feed Science 2009年第11期1卷 16-17页

作者： ZHANG Ming CHEN Li-xlang FAN Zhi-yong WU Ying-song College of Animal Science and Technology Hunan Agricultural University Changsha 410128 China

[ Objective] To study the effects of gamma-aminobutyric acid （GABA） on performance of lactating sows during heat stress. [ Metbod] A total of 14 sows at the same parity and with close expected date of childbirth and similar body we：,ght were randomly divided into control group and experimental group. They were fed a common basal diet and a GABA （300 mg/kg） supplementary diet, respectively. The trial lasted for 21 d. [ Result ] The daily feed intake, lactation yield and average daily gain of piglets in the experimental group were increased by 9.4%, 28.5% and 10.7%, respectively. The backfat of lactating sows was decreased less, and the same with the weaning-oestrus interval. The survival ratio of piglets was increased by 4.5%. Compared with the control group, the content of lactose and fat increased significantly, but other components almost did not change. [Conclusien] Supplementing GABA in diet can improve the performance of lactating sows and promote the growth of piglets effectively.

关键词： gamma-aminobutyric acid Lactating sows Piglets Performance

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Efficient gamma-aminobutyric acid bioconversion by engineered Escherichia coli

Efficient gamma-aminobutyric acid bioconversion by engineere...

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华东地区生物化学与分子生物学学会联合会2017年学术交流会暨安徽省生物化学与分子生物学学会理事会议

作者： Xinwei Yang Jie Wei Yang Ren Chongrong Ke Jia Chen Songgang Wu Jianzhong Huang National Engineering Research Center of Industrial Microbiology and Fermentation Technology

To construct a simple and efficient process for industrial production of GABA from L-glutamic acid(L-Glu) by whole-cell *** encoding glutamate decarboxylase(GAD) from Lactococcus lactis FJNUGA01 was over-expressed using the most available vector pET-28 a in *** production was enhanced by optimizing culture conditions of the catalyst,such as IPTG concertration,induction temperature and induction *** optimizing,98.4 g GABA I-1 with 96 mol%conversion within 6 h was achieved by whole-cell conversion using the cells induced with 1 mM IPTG for 12 h at30 ℃.Furthermore,when initial concentration of L-Glu was adjusted,204.12 g GABA I with 34 g I h productivity was reached using 2 M L-Glu as the *** the 6 h whole-cell bioconversion process,almost all L-Glu was converted to GABA with a conversion efficiency of-99%.The whole-cell bioconversion for GABA production was easy to construct and *** high conversion efficiency and high productivity made the GABA purification downstream and the whole process more simple and economical for industrial application.

关键词： Escherichia coli gamma-aminobutyric acid Glutamate decarboxylase Whole-cell bioconversion

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Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

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Food Science and Human Wellness 2024年第4期13卷 1987-2001页

作者： Shuhua Shan Ruopeng Yin Jiangying Shi Lizhen Zhang Jiaqi Zhou Qinqin Qiao Xiushan Dong Wenjing Zhao Zhuoyu Li Institute of Biotechnology Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of EducationShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi Bethune Hospital Shanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan 030032China Department of Biology Biological Science and Technology CollegeTaiyuan Normal UniversityJinzhong 030619China

Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota *** derived from gut microbes play essential roles in Met S prevention and ***,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of *** obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP *** protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier *** microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides *** fecal microbiota transplantation(FMT)also demonstrated this *** addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S ***,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by *** addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met *** results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

关键词： Metabolic syndrome Gut microbiota Extract of millet bran protein gamma-aminobutyric acid Gut barrier function

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