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Optimization of fermentation for γ-aminobutyric acid (GABA) production by yeast Kluyveromyces marxianus C21 in okara (soybean residue)

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Abstract

γ-Aminobutyric acid (GABA) is a non-protein amino acid with a variety of physiological functions. Recently, yeast Kluyveromyces marxianus strains involved in the catabolism and anabolism of GABA can be used as a microbial platform for GABA production. Okara, rich in nutrients, can be used as a low-cost fermentation substrate for the production of functional materials. This study first proved the advantages of the okara medium to produce GABA by K. marxianus C21 when l-glutamate (l-Glu) or monosodium glutamate (MSG) is the substrate. The highest production of GABA was obtained with 4.31 g/L at optimization condition of culture temperature 35 °C, fermentation time 60 h, and initial pH 4.0. Furthermore, adding peptone significantly increased the GABA production while glucose and vitamin B6 had no positive impact on GABA production. This research provided a powerful new strategy of GABA production by K. marxianus C21 fermentation and is expected to be widely utilized in the functional foods industry to increase GABA content for consumers as a daily supplement as suggested.

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References

  1. Kostowski W, Hamon M (1999) Anti-anxiety activity—involvement of serotonergic and GABA-ergic activity. Eur Neuropsychopharmacol. https://doi.org/10.1016/S0924-977X(99)90095-0

    Article  Google Scholar 

  2. Suwanmanon K, Hsieh P-C (2014) Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats. J Food Drug Anal 22:485–491. https://doi.org/10.1016/j.jfda.2014.03.005

    Article  CAS  PubMed  Google Scholar 

  3. Ren T, Zheng P, Zhang K, Liao J, Xiong F, Shen Q, Ma Y, Fang W, Zhu X (2021) Effects of GABA on the polyphenol accumulation and antioxidant activities in tea plants (Camellia sinensis L.) under heat-stress conditions. Plant Physiol Biochem 159:363–371. https://doi.org/10.1016/j.plaphy.2021.01.003

    Article  CAS  PubMed  Google Scholar 

  4. Ikegami R, Shimizu I, Sato T, Yoshida Y, Hayashi Y, Suda M, Katsuumi G, Li J, Wakasugi T, Minokoshi Y, Okamoto S, Hinoi E, Nielsen S, Jespersen NZ, Scheele C, Soga T, Minamino T (2018) Gamma-aminobutyric acid signaling in brown adipose tissue promotes systemic metabolic derangement in obesity. Cell Rep 24:2827-2837.e2825. https://doi.org/10.1016/j.celrep.2018.08.024

    Article  CAS  PubMed  Google Scholar 

  5. Nájera-Martínez M, López-Tapia BP, Aguilera-Alvarado GP, Madera-Sandoval RL, Sánchez-Nieto S, Giron-Pérez MI, Vega-López A (2020) Sub-basal increases of GABA enhance the synthesis of TNF-α, TGF-β, and IL-1β in the immune system organs of the Nile tilapia. J Neuroimmunol 348:577382. https://doi.org/10.1016/j.jneuroim.2020.577382

    Article  CAS  PubMed  Google Scholar 

  6. Diana M, Quílez J, Rafecas M (2014) Gamma-aminobutyric acid as a bioactive compound in foods: a review. J Funct Foods 10:407–420. https://doi.org/10.1016/j.jff.2014.07.004

    Article  CAS  Google Scholar 

  7. Small PLC, Waterman SR (1998) Acid stress, anaerobiosis and gadCB: lessons from Lactococcus lactis and Escherichia coli. Trends Microbiol 6:214–216. https://doi.org/10.1016/S0966-842X(98)01285-2

    Article  CAS  PubMed  Google Scholar 

  8. Sahab NRM, Subroto E, Balia RL, Utama GL (2020) Gamma-Aminobutyric acid found in fermented foods and beverages: current trends. Heliyon 6:e05526. https://doi.org/10.1016/j.heliyon.2020.e05526

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ohmori T, Tahara M, Ohshima T (2018) Mechanism of gamma-aminobutyric acid (GABA) production by a lactic acid bacterium in yogurt-sake. Process Biochem 74:21–27. https://doi.org/10.1016/j.procbio.2018.08.030

    Article  CAS  Google Scholar 

  10. Redruello B, Szwengiel A, Ladero V, del Rio B, Alvarez MA (2020) Identification of technological/metabolic/environmental profiles of cheeses with high GABA contents. LWT-Food Sci Technol 130:109603. https://doi.org/10.1016/j.lwt.2020.109603

    Article  CAS  Google Scholar 

  11. Hwang CE, Kim SC, Kim DH, Lee HY, Suh HK, Cho KM, Lee JH (2021) Enhancement of isoflavone aglycone, amino acid, and CLA contents in fermented soybean yogurts using different strains: screening of antioxidant and digestive enzyme inhibition properties. Food Chem 340:128199

    Article  CAS  Google Scholar 

  12. Cui Y, Miao K, Niyaphorn S, Qu X (2020) Production of gamma-aminobutyric acid from lactic acid bacteria: a systematic review. Int J Mol Sci. https://doi.org/10.3390/ijms21030995

    Article  PubMed  PubMed Central  Google Scholar 

  13. Radhika Dhakal VKB, Baek K-H (2012) Production of GABA (γ-aminobutyric acid) by microorganisms: a review. Braz J Microbiol. https://doi.org/10.1590/s1517-83822012000400001

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hsueh YH, Liaw WC, Kuo JM, Deng CS, Wu CH (2017) Hydrogel film-immobilized Lactobacillus brevis RK03 for gamma-aminobutyric acid production. Int J Mol Sci. https://doi.org/10.3390/ijms18112324

    Article  PubMed  PubMed Central  Google Scholar 

  15. Saraphanchotiwitthaya A, Sripalakit P (2018) Production of γ-aminobutyric acid from red kidney bean and barley grain fermentation by Lactobacillus brevis TISTR 860. Biocatal Agric Biotechnol 16:49–53. https://doi.org/10.1016/j.bcab.2018.07.016

    Article  Google Scholar 

  16. Tajabadi N, Ebrahimpour A, Baradaran A, Rahim RA, Mahyudin NA, Manap MY, Bakar FA, Saari N (2015) Optimization of gamma-aminobutyric acid production by Lactobacillus plantarum Taj-Apis362 from honeybees. Molecules 20:6654–6669. https://doi.org/10.3390/molecules20046654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Komatsuzaki N, Shima J, Kawamoto S, Momose H, Kimura T (2005) Production of γ-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods. Food Microbiol 22:497–504. https://doi.org/10.1016/j.fm.2005.01.002

    Article  CAS  Google Scholar 

  18. Ando A, Nakamura T (2016) Prevention of GABA reduction during dough fermentation using a Baker’s yeast dal81 mutant. J Biosci Bioeng 122:441–445. https://doi.org/10.1016/j.jbiosc.2016.03.006

    Article  CAS  PubMed  Google Scholar 

  19. Han SM, Lee JS (2017) Production and its anti-hyperglycemic effects of gamma-aminobutyric acid from the wild yeast strain Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1. Mycobiology 45:199–203. https://doi.org/10.5941/MYCO.2017.45.3.199

    Article  PubMed  PubMed Central  Google Scholar 

  20. Perpetuini G, Tittarelli F, Battistelli N, Suzzi G, Tofalo R (2020) Gamma-aminobutyric acid production by Kluyveromyces marxianus strains. J Appl Microbiol 129:1609–1619. https://doi.org/10.1111/jam.14736

    Article  CAS  PubMed  Google Scholar 

  21. Pentjuss A, Stalidzans E, Liepins J, Kokina A, Martynova J, Zikmanis P, Mozga I, Scherbaka R, Hartman H, Poolman MG, Fell DA, Vigants A (2017) Model-based biotechnological potential analysis of Kluyveromyces marxianus central metabolism. J Ind Microbiol Biotechnol 44:1177–1190. https://doi.org/10.1007/s10295-017-1946-8

    Article  CAS  PubMed  Google Scholar 

  22. Guneser O, Karagul-Yuceer Y, Wilkowska A, Kregiel D (2016) Volatile metabolites produced from agro-industrial wastes by Na-alginate entrapped Kluyveromyces marxianus Braz. J Microbiol 47(965):972. https://doi.org/10.1016/j.bjm.2016.07.018

    Article  CAS  Google Scholar 

  23. Swallah MS, Fan H, Wang S, Yu H, Piao C (2021) Prebiotic impacts of soybean residue (okara) on Eubiosis/Dysbiosis condition of the gut and the possible effects on liver and kidney functions. Molecules. https://doi.org/10.3390/molecules26020326

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li B, Lu F, Nan H, Liu Y (2012) Isolation and structural characterisation of okara polysaccharides. Molecules 17:753–761. https://doi.org/10.3390/molecules17010753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hu Y, Piao C, Chen Y, Zhou Y, Wang D, Yu H, Xu B (2019) Soybean residue (okara) fermentation with the yeast Kluyveromyces marxianus. Food Biosci 31:100439. https://doi.org/10.1016/j.fbio.2019.100439

    Article  CAS  Google Scholar 

  26. Queiroz Santos VA, Nascimento CG, Schmidt CAP, Mantovani D, Dekker RFH, da Cunha MAA (2018) Solid-state fermentation of soybean okara: isoflavones biotransformation, antioxidant activity and enhancement of nutritional quality. LWT-Food Sci Technol 92:509–515. https://doi.org/10.1016/j.lwt.2018.02.067

    Article  CAS  Google Scholar 

  27. Wang X, Zhang Y, Li Y, Yu H, Wang Y, Piao C (2020) Insoluble dietary fibre from okara (soybean residue) modified by yeast Kluyveromyces marxianus. LWT-Food Sci Technol 134:110252. https://doi.org/10.1016/j.lwt.2020.110252

    Article  CAS  Google Scholar 

  28. Su Min PC, Yang Deok Chun, Qi Chu, Yuhua Wang, Shang Wang, Chen Yue HU, Yang Huo Yue (2018) Screening and identification of β-glucosidase-producing yeast and its application in the bioconversion of ginsenoside Rg3. Food Sci 39:172–178. https://doi.org/10.7506/spkx1002-6630-201814026

    Article  Google Scholar 

  29. Wenyan Ma JZ, Shu L, Tan X, An Ya, Yang X, Wang D, Gao Q (2020) Optimization of spray drying conditions for the green manufacture of γ-aminobutyric acid-rich powder from Lactobacillus brevis fermentation broth. Biochem Eng J. https://doi.org/10.1016/j.bej.2020.107499

    Article  Google Scholar 

  30. Cho YR, Chang JY, Chang HC (2007) Production of γ-aminobutyric acid (GABA) by Lactobacillus buchneri isolated from Kimchi and its neuroprotective effect on neuronal cells. J Microbiol Biotechnol 17:104–109. https://doi.org/10.1016/j.mimet.2006.07.012

    Article  CAS  PubMed  Google Scholar 

  31. Chi Z, Dai Y, Cao S, Wei Y, Shao X, Huang X, Xu F, Wang H (2021) Exogenous calcium chloride (CaCl2) promotes γ-aminobutyric acid (GABA) accumulation in fresh-cut pears. Postharvest Biol Technol 174:111446. https://doi.org/10.1016/j.postharvbio.2020.111446

    Article  CAS  Google Scholar 

  32. Marino A, Bellinghieri V, Nostro A, Miceli N, Taviano MF, Guvenc A, Bisignano G (2010) In vitro effect of branch extracts of Juniperus species from Turkey on Staphylococcus aureus biofilm. FEMS Immunol Med Microbiol 59:470–476. https://doi.org/10.1111/j.1574-695X.2010.00705

    Article  CAS  PubMed  Google Scholar 

  33. Linares DM, O’Callaghan TF, O’Connor PM, Ross RP, Stanton C (2016) Streptococcus thermophilus APC151 strain is suitable for the manufacture of naturally GABA-enriched bioactive yogurt. Front Microbiol 7:1876. https://doi.org/10.3389/fmicb.2016.01876

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gangaraju D, Murty VR, Prapulla SG (2013) Probiotic-mediated biotransformation of monosodium glutamate to γ-aminobutyric acid: differential production in complex and minimal media and kinetic modelling. Ann Microbiol 64:229–237. https://doi.org/10.1007/s13213-013-0655-4

    Article  CAS  Google Scholar 

  35. Yunes RA, Poluektova EU, Dyachkova MS, Klimina KM, Kovtun AS, Averina OV, Orlova VS, Danilenko VN (2016) GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42:197–204. https://doi.org/10.1016/j.anaerobe.2016.10.011

    Article  CAS  PubMed  Google Scholar 

  36. Hasegawa M, Yamane D, Funato K, Yoshida A, Sambongi Y (2018) Gamma-aminobutyric acid fermentation with date residue by a lactic acid bacterium, Lactobacillus brevis. J Biosci Bioeng 125:316–319. https://doi.org/10.1016/j.jbiosc.2017.10.003

    Article  CAS  PubMed  Google Scholar 

  37. Hamoudi Mousah PJaML (1987) The quantification of gamma-aminobutyric acid in the cerebrospinal fluid by a radioreceptorassay. Clin Chim Acta 170:151–160. https://doi.org/10.1016/0009-8981(87)90123-9

    Article  Google Scholar 

  38. Kamisaki Y, Itoh T (1990) Determination of y-aminobutyric acid in human cerebrospinal fluid by isocratic high-performance liquid chromatography. J Chromatogr 529:417–423. https://doi.org/10.1016/S0378-4347(00)83848-7

    Article  CAS  PubMed  Google Scholar 

  39. Rayavarapu B, Tallapragada P, Usha MS (2019) Statistical optimization of γ-aminobutyric acid production by response surface methodology and artificial neural network models using Lactobacillus fermentum isolated from palm wine. Biocatal Agric Biotechnol 22:101362. https://doi.org/10.1016/j.bcab.2019.101362

    Article  Google Scholar 

  40. Chaoyang Y, Xu L, Yuke M, Kaixuan J, Yuanxiu W (2020) Optimization of berthelot colorimetric method for determination of γ-aminobutyric acid. J Univ Jinan 34:306–312. https://doi.org/10.13349/j.cnki.jdxbn.2020.03.016. (In Chinese)

    Article  CAS  Google Scholar 

  41. Le Hong P, Parmentier N, Le Trung T, Raes K (2021) Evaluation of using a combination of enzymatic hydrolysis and lactic acid fermentation for γ-aminobutyric acid production from soymilk. LWT-Food Sci Technol 142:111044. https://doi.org/10.1016/j.lwt.2021.111044

    Article  CAS  Google Scholar 

  42. Karim A, Gerliani N, Aider M (2020) Kluyveromyces marxianus: an emerging yeast cell factory for applications in food and biotechnology. Int J Food Microbiol 333:108818. https://doi.org/10.1016/j.ijfoodmicro.2020.108818

    Article  CAS  PubMed  Google Scholar 

  43. Li H, Qiu T, Huang G, Cao Y (2010) Production of gamma-aminobutyric acid by Lactobacillus brevis NCL912 using fed-batch fermentation. Microb Cell Fact 9:85. https://doi.org/10.1186/1475-2859-9-85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kim JY, Lee MY, Ji GE, Lee YS, Hwang KT (2009) Production of gamma-aminobutyric acid in black raspberry juice during fermentation by Lactobacillus brevis GABA100. Int J Food Microbiol 130:12–16. https://doi.org/10.1016/j.ijfoodmicro.2008.12.028

    Article  CAS  PubMed  Google Scholar 

  45. Long R, Yang W, Huang G (2020) Optimization of fermentation conditions for the production of epothilone B. Chem Biol Drug Des 96:768–772. https://doi.org/10.1111/cbdd.13682

    Article  CAS  PubMed  Google Scholar 

  46. Foukis A, Stergiou PY, Theodorou LG, Papagianni M, Papamichael EM (2012) Purification, kinetic characterization and properties of a novel thermo-tolerant extracellular protease from Kluyveromyces marxianus IFO 0288 with potential biotechnological interest. Bioresour Technol 123:214–220. https://doi.org/10.1016/j.biortech.2012.06.090

    Article  CAS  PubMed  Google Scholar 

  47. Kim D-H, Dasagrandhi C, Park S-K, Eom S-H, Huh M-K, Mok J-S, Kim Y-M (2018) Optimization of gamma-aminobutyric acid production using sea tangle extract by lactic acid bacterial fermentation. LWT-Food Sci Technol 90:636–642. https://doi.org/10.1016/j.lwt.2018.01.011

    Article  CAS  Google Scholar 

  48. Li H, Qiu T, Gao D, Cao Y (2010) Medium optimization for production of gamma-aminobutyric acid by Lactobacillus brevis NCL912. Amino Acids 38:1439–1445. https://doi.org/10.1007/s00726-009-0355-3

    Article  CAS  PubMed  Google Scholar 

  49. Chen L, Alcazar J, Yang T, Lu Z, Lu Y (2018) Optimized cultural conditions of functional yogurt for gamma-aminobutyric acid augmentation using response surface methodology. J Dairy Sci 101:10685–10693. https://doi.org/10.3168/jds.2018-15391

    Article  CAS  PubMed  Google Scholar 

  50. Park SJ, Kim DH, Kang HJ, Shin M, Yang S-Y, Yang J, Jung YH (2021) Enhanced production of γ-aminobutyric acid (GABA) using Lactobacillus plantarum EJ2014 with simple medium composition. LWT-Food Sci Technol 137:110443. https://doi.org/10.1016/j.lwt.2020.110443

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are grateful to Jilin Province Innovation Center for Biological Food and Manufacturing Technology of China for their excellent technical assistance. Financial support was provided China Agriculture Research System of MOF and MARA (CARS-04) and Jilin Provincial Science and Technology Department (20170312022ZX).

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China Agriculture Research System of MOF and MARAJilin Provincial Science and Technology Department 20170312022ZX.

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CP and HY designed the study; LZ, YY and WD acquired and analyzed the data; LZ, CP and XW drafted the manuscript; all authors critically revised the manuscript and approved the final version of the manuscript to be submitted.

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Correspondence to Chunhong Piao or Hansong Yu.

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We believe that this manuscript is appropriate for publication on bioprocess and biosystem engineering, because our research is aimed to investigate. On behalf of, and having obtained permission from all the authors, we declare that: (a) the material has not been published in whole or in part elsewhere, (b) the paper is not currently being considered for publication elsewhere, (c) all authors have been personally and actively involved in substantive work leading to the report, and will hold themselves jointly and individually responsible for its content, (d) all relevant ethical safeguards have been met in relation to subject protection, (e) all authors declare no conflict of interests.

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Zhang, L., Yue, Y., Wang, X. et al. Optimization of fermentation for γ-aminobutyric acid (GABA) production by yeast Kluyveromyces marxianus C21 in okara (soybean residue). Bioprocess Biosyst Eng 45, 1111–1123 (2022). https://doi.org/10.1007/s00449-022-02702-2

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