Аффилиация
a Северо-Кавказский федеральный университет, Ставрополь
Все права защищены ©Рябцева и др. Это статья с открытым доступом, распространяемая на условиях международной лицензии Creative Commons Attribution 4.0. (
http://creativecommons.org/licenses/by/4.0/), позволяет другим распространять, перерабатывать, исправлять и развивать произведение, даже в коммерческих целях, при условии указания автора произведения.
Аннотация
Галактоолигосахариды обладают пребиотической активностью, их получают из лактозы с использованием бета-галактозидаз бактериального или грибного происхождения. Цель обзора – выявление и анализ факторов, влияющих на биосинтез и очистку галактоолигосахаридов, с использованием бета-галактозидаз дрожжей рода Kluyveromyces, а также перспективных направлений исследований в этой области.
Объектами исследования стали научные публикации по вопросам получения галактоолигосахаридов с использованием бета-галактозидаз дрожжей. Для поиска информации были использованы международные базы данных Scopus, Web of Science, PubMed, eLIBRARY.RU Для анализа было отобрано 87 источников, в основном статьи в рецензируемых журналах, опубликованные преимущественно за последние 10 лет.
Выбор фермента и формы его применения, оптимизация условий биосинтеза и очистки являются наиболее важными для регулирования выхода, состава и свойств анализируемых веществ. Бета-галактозидазы из Kluyveromyces могут одновременно катализировать реакции гидролиза и трансгалактозилирования. Условия протекания процессов биосинтеза галактоолигосахаридов с этими ферментами широко варьируют в разных публикациях, как и их выход, но чаще всего этот показатель не превышает 30–40 %, при этом общая конверсия лактозы достигает 80–90 %. Применение бета-галактозидаз Kluyveromyces в виде цельноклеточных ферментов, в иммобилизованной форме или совместно с другими ферментами позволяет улучшить экономические показатели процессов биосинтеза и / или выход и / или структуру рассматриваемых веществ. Прямой их синтез в молоке или сыворотке дает возможность получать новые функциональные молочные продукты и добавки. Селективная биоконверсия с дрожжами Kluyveromyces позволяет повысить чистоту галактоолигосахаридов до 90 % экономически выгодным и экологически безопасным путем.
К перспективным направлениям можно отнести использование побочного молочного сырья для получения продуктов с галактоолигосахаридами, комбинированное применение ферментов разных продуцентов, а также комплексное применение бета-галактозидаз Kluyveromyces для их биосинтеза и очистки.
Ключевые слова
Лактоза,
бета-галактозидазы,
Kluyveromyces,
трансгалактозилирование,
гидролиз,
молочная сыворотка,
очистка
СПИСОК ЛИТЕРАТУРЫ
- Souza AFC, Gabardo S, de Jesus Silva Coelho R. Galactooligosaccharides: Physiological benefits, production strategies, and industrial application. Journal of Biotechnology. 2022;359:116-129. https://doi.org/10.1016/j.jbiotec.2022.09.020
- Ambrogi V, Bottacini F, Cao L, Kuipers B, Schoterman M, et al. Galacto-oligosaccharides as infant prebiotics: Production, application, bioactive activities and future perspectives. Critical Reviews in Food Science and Nutrition. 2023;63(6): 753-766. https://doi.org/10.1080/10408398.2021.1953437
- Global galactooligosaccharides market overview. Market Research Future. [cited 2025 Mar 27]. Available from: https://www.marketresearchfuture.com/reports/galactooligosaccharides-market-22433
- Martins GN, Ureta MM, Tymczyszyn EE, Castilho PC, Gomez-Zavaglia A. Technological aspects of the production of fructo and galacto-oligosaccharides. Enzymatic synthesis and hydrolysis. Frontiers in Nutrition. 2019;6:78. https:// doi.org/10.3389/fnut.2019.00078
- Guerrero C, Vera C, Illanes A. Optimisation of synthesis of oligosaccharides derived from lactulose (fructosyl-galacto-oligosaccharides) with β-galactosidases of different origin. Food Chemistry. 2013;138(4):2225-2232. https://doi.org/10.1016/ j.foodchem.2012.10.128
- Arnold JW, Whittington HD, Dagher SF, Roach J, Azcarate-Peril MA, et al. Safety and modulatory effects of humanized galacto-oligosaccharides on the gut microbiome. Frontiers in Nutrition. 2021;8:640100. https://doi.org/10.3389/ fnut.2021.640100
- Ignatova I, Arsov A, Petrova P, Petrov K. Prebiotic effects of α- and β-galactooligosaccharides: The structure-function relation. Molecules. 2025;30(4):803. https://doi.org/10.3390/molecules30040803
- Deshmukh N, Rao PS, Sharma H, Sathish Kumar MH, Naik NL, et al. Waste to nutrition: The evolution of whey, a byproduct to galactooligosaccharides production. Food Chemistry Advances. 2024;4:100642. https://doi.org/10.1016/j.focha. 2024.100642
- Maraz A, Kovacs Z, Benjamins E, Pazmandi M. Recent developments in microbial production of high-purity galacto-oligosaccharides. World Journal of Microbiology and Biotechnology. 2022;38(6):95. https://doi.org/10.1007/s11274-022-03279-4
- Zolnere K, Ciprovica I. The comparison of commercially available β-galactosidases for dairy industry: Review. Food Science. Research for Rural Development. 2017;1:215-222. https://doi.org/10.22616/rrd.23.2017.032
- Chen X, de Vos P. Structure-function relationship and impact on the gut-immune barrier function of non-digestible carbohydrates and human milk oligosaccharides applicable for infant formula. Critical Reviews in Food Science and Nutrition. 2024;64(23):8325-8345. https://doi.org/10.1080/10408398.2023.2199072
- Vera C, Guerrero C, Illanes A. Trends in lactose-derived bioactives: Synthesis and purification. Systems Microbiology and Biomanufacturing. 2022;2:393-412. https://doi.org/10.1007/s43393-021-00068-2
- Torres DPM, Goncalves M do PF, Teixeira JA, Rodrigues LR. Galacto-oligosaccharides: Production, properties, applications, and significance as prebiotics. Comprehensive Reviews in Food Science and Food Safety. 2010;9(5):438-454. https://doi.org/10.1111/j.1541-4337.2010.00119.x
- de Albuquerque TL, de Sousa M, Gomes E, Silva NC, Girao Neto CAC, et al. β-galactosidase from Kluyveromyces lactis: Characterization, production, immobilization and applications - A review. International Journal of Biological Macromolecules. 2021;191:881-898. https://doi.org/10.1016/j.ijbiomac.2021.09.133
- Лютова Л. В., Наумов Г. И., Шнырева А. В., Наумова Е. С. Молекулярный полиморфизм β-галактозидазных генов LAC4 у молочных и природных штаммов дрожжей Kluyveromyces. Молекулярная биология. 2021. Т. 55. № 1. С. 75-85. https://doi.org/10.31857/S0026898421010109
- Лютова Л. В., Наумова Е. С. Межштаммовая гибридизация дрожжей Kluyveromyces lactis для создания штаммов, активно сбраживающих лактозу. Биотехнология. 2021. Т. 37. № 4. С. 43-50. https://elibrary.ru/XZBKCB
- Лютова Л. В., Наумова Е. С. Сравнительный анализ сбраживания лактозы и ее компонентов, глюкозы и галактозы, межштаммовыми гибридами молочных дрожжей Kluyveromyces lactis. Биотехнология. 2023. T. 39. № 1. С. 3-11. https://doi.org/10.56304/s0234275823010064
- Rodriguez-Colinas B, Fernandez-Arrojo L, Ballesteros AO, Plou FJ. Galactooligosaccharides formation during enzymatic hydrolysis of lactose: Towards a prebiotic-enriched milk. Food Chemistry. 2014;145:388-394. https://doi.org/10.1016/j.foodchem.2013.08.060
- Liburdi K, Esti M. Galacto-oligosaccharide (GOS) synthesis during enzymatic lactose-free milk production: State of the art and emerging opportunities. Beverages. 2022;8(2):21. https://doi.org/10.3390/beverages8020021
- Fischer C, Kleinschmidt T. Synthesis of galactooligosaccharides in milk and whey: A review. Comprehensive Reviews in Food Science and Food Safety. 2018;17(3):678-697. https://doi.org/10.1111/1541-4337.12344
- Ganzle MG, Haase G, Jelen P. Lactose: Crystallization, hydrolysis and value-added derivatives. International Dairy Journal. 2008;18(7):685-694. https://doi.org/10.1016/j.idairyj.2008.03.003
- Guerrero C, Vera C, Conejeros R, Illanes A. Transgalactosylation and hydrolytic activities of commercial preparations of β-galactosidase for the synthesis of prebiotic carbohydrates. Enzyme and Microbial Technology. 2015;70:9-17. https:// doi.org/10.1016/j.enzmictec.2014.12.006
- Boger M, van Leeuwen SS, van Bueren AL, Dijkhuizen L. Structural identity of galactooligosaccharide molecules selectively utilized by single cultures of probiotic bacterial strains. Journal of Agricultural and Food Chemistry. 2019;67(50):13969- 13977. https://doi.org/10.1021/acs.jafc.9b05968
- van Leeuwen SS, Kuipers BJH, Dijkhuizen L, Kamerling JP. Comparative structural characterization of 7 commercial galacto-oligosaccharide (GOS) products. Carbohydrate Research. 2016;425:48-58. https://doi.org/10.1016/j.carres.2016.03.006
- Logtenberg MJ, Donners KMH, Vink JCM, van Leeuwen SS, de Waard P, et al. Touching the high complexity of prebiotic vivinal galacto-oligosaccharides using porous graphitic carbon ultra-high-performance liquid chromatography coupled to mass spectrometry. Journal of Agricultural and Food Chemistry. 2020;68(29):7800-7808. https://doi.org/10.1021/acs.jafc.0c02684
- Kruschitz A, Nidetzky B. Downstream processing technologies in the biocatalytic production of oligosaccharides. Biotechnology Advances. 2020;43:107568. https://doi.org/10.1016/j.biotechadv.2020.107568
- Cao T, Pazmandi M, Galambos I, Kovacs Z. Continuous production of galacto-oligosaccharides by an enzyme membrane reactor utilizing free enzymes. Membranes. 2020;10(9):203. https://doi.org/10.3390/membranes10090203
- Botelho VA, Mateus M, Petrus JCC, de Pinho MN. Membrane bioreactor for simultaneous synthesis and fractionation of oligosaccharides. Membranes. 2022;12(2):171. https://doi.org/10.3390/membranes12020171
- Cordova A, Astudillo C, Giorno L, Guerrero C, Conidi C, et al. Nanofltration potential for the purifcation of highly concentrated enzymatically produced oligosaccharides. Food and Bioproducts Processing 2016;98:50-61. https://doi.org/10.1016/ j.fbp.2015.11.005
- Information on EC 3.2.1.23 - beta-galactosidase. BRENDA. [cited 2025 Apr 21]. (In Russ.) Available from: https://www.brenda-enzymes.org/enzyme.php?ecno=3.2.1.23
- Храмцов А. Г., Рябцева С. А., Панфилова А. А., Родная А. Б., Лодыгин А. Д. Применение дрожжей-продуцентов бета-галактозидаз для получения галактоолигосахаридов из лактозосодержащего сырья. Хранение и переработка сельхозсырья. 2012. № 8. С. 36-39. https://elibrary.ru/PDHUFT
- Qiu Y, Lei P, Wang R, Sun L, Luo Z, et al. Kluyveromyces as promising yeast cell factories for industrial bio¬production: From bio-functional design to applications. Biotechnology Advances. 2023;64:108125. https://doi.org/10.1016/j.biotechadv.2023.108125
- Allende A, Alvarez-Ordonez A, Bolton D, Bover-Cid S, Chemaly M, et al. Update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA 15: Suitability of taxonomic units notified to EFSA until September 2021. EFSA Journal. 2022;20(1):e07045.
- Spohner SC, Schaum V, Quitmann H, Czermak P. Kluyveromyces lactis: An emerging tool in biotechnology. Journal of Biotechnology. 2016;222:104-116. https://doi.org/10.1016/j.jbiotec.2016.02.023
- Reina-Posso D, Gonzales-Zubiate FA. Expanding horizons: The untapped potential of Kluyveromyces marxianus in biotechnological applications. Fermentation. 2025;11(2):98. https://doi.org/10.3390/fermentation11020098
- Pereira-Rodriguez A, Fernandez-Leiro R, Gonzalez-Siso MI, Cerdan ME, Becerra M, et al. Structural basis of specificity in tetrameric Kluyveromyces lactis β-galactosidase. Journal of Structural Biology. 2012;177(2):392-401. https://doi.org/10.1016/j.jsb.2011.11.031
- P00723 (BGAL_KLULA). SWISS-MODEL. [cited 2025 Apr 21]. (In Russ.) Available from: https://swissmodel.expasy.org/repository/uniprot/P00723?template=3ob8
- O’Connell S, Walsh G. Purification and properties of a β-galactosidase with potential application as a digestive supplement. Applied Biochemistry and Biotechnology. 2007;141:1-14. https://doi.org/10.1007/s12010-007-9206-4
- Yin H, Bultema JB, Dijkhuizen L, van Leeuwen SS. Reaction kinetics and galactooligosaccharide product profiles of the в-galactosidases from Bacillus circulans, Kluyveromyces lactis and Aspergillus oryzae. Food Chemistry. 2017;225:230-238. https://doi.org/10.1016/j.foodchem.2017.01.030
- Gonzalez-Delgado I, Lopez-Munoz M-J, Morales G, Segura Y. Optimisation of the synthesis of high galacto-oligo-saccharides (GOS) from lactose with β-galactosidase from Kluyveromyces lactis. International Dairy Journal. 2016;61:211-219. https://doi.org/10.1016/j.idairyj.2016.06.007
- Rico-Rodriguez F, Noriega MA, Lancheros R, Serrato-Bermudez JC. Kinetics of galactooligosaccharide (GOS) production with two β-galactosidases combined: Mathematical model and raw material effects. International Dairy Journal. 2021;118:105015. https://doi.org/10.1016/j.idairyj.2021.105015
- Fischer C, Kleinschmidt T. Synthesis of galactooligosaccharides using sweet and acid whey as a substrate. International Dairy Journal. 2015;48:15-22. https://doi.org/10.1016/j.idairyj.2015.01.003
- Frenzel M, Zerge K, Clawin-Radecker I, Lorenzen PC. Comparison of the galacto-oligosaccharide forming activity of different β-galactosidases. LWT - Food Science and Technology. 2015;60(2, Part 1):1068-1071. https://doi.org/10.1016/ j.lwt.2014.10.064
- Botvynko A, Bednarova A, Henke S, Shakhno N, Curda L. Production of galactooligosaccharides using various combinations of the commercial β-galactosidases. Biochemical and Biophysical Research Communications. 2019;517(4):762-766. https://doi.org/10.1016/j.bbrc.2019.08.001
- Singh P, Arora S, Rao PS, Kathuria D, Sharma V, et al. Effect of process parameters on the β-galactosidase hydrolysis of lactose and galactooligosaccharide formation in concentrated skim milk. Food Chemistry. 2022;393:133355. https:// doi.org/10.1016/j.foodchem.2022.133355
- Mano MCR, Paulino BN, Pastore GM. Whey permeate as the raw material in galacto-oligosaccharide synthesis using commercial enzymes. Food Research International. 2019;124:78-85. https://doi.org/10.1016/j.foodres.2018.09.019
- Padilla B, Ruiz-Matute AI, Belloch C, Cardelle-Cobas A, Corzo N, et al. Evaluation of oligosaccharide synthesis from lactose and lactulose using β-galactosidases from Kluyveromyces isolated from artisanal cheeses. Journal of Agricultural and Food Chemistry. 2012;60(20):5134-5141. https://doi.org/10.1021/jf300852s
- Petrova VY, Kujumdzieva AV. Thermotolerant yeast strains producers of galacto-oligosaccharides. Biotechnology & Biotechnological Equipment. 2010;24(1):1612-1619. https://doi.org/10.2478/V10133-010-0014-6
- Srivastava A, Mishra S, Chand S. Synthesis of galacto-oligosaccharides from lactose using immobilized cells of Kluyveromyces marxianus NCIM 3551. Journal of Molecular Catalysis B: Enzymatic. 2016;123:147-153. https://doi.org/ 10.1016/j.molcatb.2015.11.017
- Srivastava A, Rastogi A, Jaswal AS, Sahu JK, Agarwal GP, et al. Nanofiltration-based purification process for whole-cell transformed prebiotic galactooligosaccharides. Bioprocess and Biosystems Engineering. 2025;48:621-631. https:// doi.org/10.1007/s00449-025-03132-6
- Srivastava A, Mishra S, Chand S. Transgalactosylation of lactose for synthesis of galacto-oligosaccharides using Kluyveromyces marxianus NCIM 3551. New Biotechnology. 2015;32(4):412-418. https://doi.org/10.1016/j.nbt.2015.04.004
- Botvynko A, Synytsya A, Curda L. Synthesis of galactooligosaccharides with four β-galactosidases: Structural comparison of the products by HPLC, ESI-MS and NMR. Biochemical and Biophysical Research Communications. 2025;744:151204. https://doi.org/10.1016/j.bbrc.2024.151204
- Rodriguez-Colinas B, de Abreu MA, Fernandez-Arrojo L, de Beer R, Poveda A, et al. Production of galacto-oligosaccharides by the β-galactosidase from Kluyveromyces lactis: Comparative analysis of permeabilized cells versus soluble enzyme. Journal of Agricultural and Food Chemistry. 2011;59(19):10477-10484. https://doi.org/10.1021/jf2022012
- van Trijp MPH, Rios-Morales M, Logtenberg MJ, Keshtkar S, Afman LA, et al. Detailed analysis of prebiotic fructo- and galacto-oligosaccharides in the human small intestine. Journal of Agricultural and Food Chemistry. 2024;72(38):21152-21165. https://doi.org/10.1021/acs.jafc.4c03881
- Ferreira-Lazarte A, Gallego-Lobillo P, Moreno FJ, Villamiel M, Hernandez-Hernandez O. In vitro digestibility of galactooligosaccharides: Effect of the structural features on their intestinal degradation. Journal of Agricultural and Food Chemistry. 2019;67(16):4662-4670. https://doi.org/10.1021/acs.jafc.9b00417
- Akbari P, Fink-Gremmels J, Willems RHAM, Difilippo E, Schols HA, et al. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: Insight into the role of structure and size. European Journal of Nutrition. 2017;56(5):1919-1930. https://doi.org/10.1007/s00394-016-1234-9
- Figueroa-Lozano S, Ren C, Yin H, Pham H, van Leeuwen S, et al. The impact of oligosaccharide content, glycosidic linkages and lactose content of galacto-oligosaccharides (GOS) on the expression of mucus-related genes in goblet cells. Food & Function. 2020;11(4):3506-3515. https://doi.org/10.1039/d0fo00064g
- Teymennet-Ramnez KV, Martinez-Morales F, Trejo-Hernandez MR. Yeast surface display system: Strategies for improvement and biotechnological applications. Frontiers in Bioengineering and Biotechnology. 2022;9:794742. https://doi.org/10.3389/fbioe.2021.794742
- Sun H, You S, Wang M, Qi W, Su R, et al. Recyclable strategy for the production of high-purity galacto-oligosaccharides by Kluyveromyces lactis. Journal of Agricultural and Food Chemistry. 2016;64(28):5679-5685. https://doi.org/10.1021/acs.jafc.6b01531
- Gonzalez-Catano F, Tovar-Castro L, Castano-Tostado E, Regalado-Gonzalez C, Garcia-Almendarez B, et al. Im¬provement of covalent immobilization procedure of β-galactosidase from Kluyveromyces lactis for galactooligosaccharides production: Modeling and kinetic study. Biotechnology Progress. 2017;33(6):1568-1578. https://doi.org/10.1002/btpr.2509
- Misson M, Dai S, Jin B, Chen BH, Zhang H. Manipulation of nanofiber-based β-galactosidase nanoenvironment for enhancement of galacto-oligosaccharide production. Journal of Biotechnology. 2016;222:56-64. https://doi.org/10.1016/j.jbiotec.2016.02.014
- Misson M, Jin B, Dai S, Zhang H. Interfacial biocatalytic performance of nanofiber-supported β-galactosidase for production of galacto-oligosaccharides. Catalysts. 2020;10(1):81. https://doi.org/10.3390/catal10010081
- Majore K, Ciprovica I. Bioconversion of lactose into glucose-galactose syrup by two-stage enzymatic hydrolysis. Foods. 2022;11(3):400. https://doi.org/10.3390/foods11030400
- Bolognesi LS, Gabardo S, Dall Cortivo PR, Ayub MAZ. Biotechnological production of galactooligosaccharides (GOS) using porungo cheese whey. Food Science and Technology. 2022;42:e64520. https://doi.org/10.1590/fst.64520
- Chenafa A, Abdo AAA, Mahdi AA, Zhang Q, Chen C, et al. Functionalized electrospun nanofibers to enhance β-Galactosidase immobilization and catalytic activity for efficient galactooligosaccharide synthesis. International Journal of Biological Macromolecules. 2024;270:132312. https://doi.org/10.1016/j.ijbiomac.2024.132312
- Xuan Z, Wang K, Duan F, Lu L. Non-carrier immobilization of yeast cells by genipin crosslinking for the synthesis of prebiotic galactooligosaccharides from plant-derived galactose. International Journal of Biological Macromolecules. 2024; 277(Part 1):133991. https://doi.org/10.1016/j.ijbiomac.2024.133991
- Ren H, Fei J, Shi X, Zhao T, Cheng H, et al. Continuous ultrafiltration membrane reactor coupled with nanofiltration for the enzymatic synthesis and purification of galactosyl-oligosaccharides. Separation and Purification Technology. 2015;144: 70-79. https://doi.org/10.1016/j.seppur.2015.02.020
- Рябцева С. А., Котова А. А., Скрипнюк А. А. Синтез галактоолигосахаридов с использованием дрожжей Kl. marxianus и термофильного стрептококка. Молочная промышленность. 2017. № 6. С. 62-64. https://elibrary.ru/YULXGF
- Fischer C, Kleinschmidt T. Combination of two β-galactosidases during the synthesis of galactooligosaccharides may enhance yield and structural diversity. Biochemical and Biophysical Research Communications. 2018;506(1):211-215. https://doi.org/10.1016/j.bbrc.2018.10.091
- Fischer C, Kleinschmidt T. Effect of glucose depletion during the synthesis of galactooligosaccharides using a trienzymatic system. Enzyme and Microbial Technology. 2019;121:45-50. https://doi.org/10.1016/j.enzmictec.2018.10.009
- Rico-Rodriguez F, Serrato JC, Montilla A, Villamiel M. Impact of ultrasound on galactooligosaccharides and gluconic acid production throughout a multienzymatic system. Ultrasonics Sonochemistry. 2018;44:177-183. https://doi.org/10.1016/j.ultsonch.2018.02.022
- Ponnusamy V, Sankaranarayanan M. Targeted gene manipulation of Leloir pathway genes for the constitutive expression of β-galactosidase and its transgalactosylation product galacto-oligosaccharides from Kluyveromyces lactis GG799 and knockout strains. Enzyme and Microbial Technology. 2023;169:110263. https://doi.org/10.1016/j.enzmictec.2023.110263
- Kaczynski LK, Cais-Sokolinska D, Szwengiel A. Kinetics of lactose hydrolysis and galactooligosaccharides formation in beverages based on goat’s milk and its permeate. Food Science and Biotechnology. 2019;28(5):1529-1534. https://doi.org/ 10.1007/s10068-019-00600-0
- Limnaios A, Tsevdou M, Tsika E, Korialou N, Zerva A, et al. Production of prebiotic galacto-oligosaccharides from acid whey catalyzed by a novel β-galactosidase from Thermothielavioides terrestris and commercial lactases: A comparative study. Catalysts. 2023;13(10):1360. https://doi.org/10.3390/catal13101360
- Limnaios A, Tsevdou M, Zafeiri E, Topakas E, Taoukis P. Cheese and yogurt by-products as valuable ingredients for the production of prebiotic oligosaccharides. Dairy. 2024;5(1):78-92. https://doi.org/10.3390/dairy5010007
- Guron GKP, Hotchkiss ATJr, Bodnar BH, Harron A, Renye JAJr, et al. Oligosaccharide production using β-galactosidase from Lactobacillus bulgaricus and Kluyveromyces lactis in sweetened reconstituted nonfat dry milk. Journal of Dairy Science. 2025;108(6):5696-5704. https://doi.org/10.3168/jds.2025-26396
- Hoyos JD, Noriega MA, Riascos CAM. Modeling and simulation of the enzymatic kinetics for the production of Galactooligosaccharides (GOS) using an Artificial Neural Network hybrid model. Digital Chemical Engineering. 2023;9:100132. https://doi.org/10.1016/j.dche.2023.100132
- Rico-Rodriguez F, Villamiel M, Ruiz-Aceituno L, Serrato JC, Montilla A. Effect of the lactose source on the ultrasound-assisted enzymatic production of galactooligosaccharides and gluconic acid. Ultrasonics Sonochemistry. 2020;67:104945. https://doi.org/10.1016/j.ultsonch.2019.104945
- Cordova A, Astudillo-Castro C, Henriquez P, Manriquez N, Nunez H, et al. Ultrasound-assisted enzymatic synthesis of galacto-oligosaccharides using native whey with two commercial β-galactosidases: Aspergillus oryzae and Kluyveromyces var lactis. Food Chemistry. 2023;426:136526. https://doi.org/10.1016/j.foodchem.2023.136526
- Jarrard TR, Brock E, Hansen LD, Kenealey JD. Measuring β-galactosidase activity in opaque dairy solutions under optimum conditions for galactooligosaccharide synthesis by isothermal titration calorimetry. Journal of Dairy Science. 2023; 106(12):8312-8320. https://doi.org/10.3168/jds.2023-23400
- Yeo I-S, Yoon Y-J, Seo N, An HJ, Kim J-H. Biopurification of oligosaccharides by immobilized Kluyveromyces lactis. Applied Sciences. 2019;9(14):2845. https://doi.org/10.3390/app9142845
- Tokosova S, Hronska H, Rosenberg M. Production of high-content galacto-oligosaccharides mixture using β-galactosidase and Kluyveromyces marxianus entrapped in polyvinylalcohol gel. Chemical Papers. 2016;70:1445-1451. https://doi.org/ 10.1515/chempap-2016-0081
- Santibanez L, Guerrero C, Illanes A. Raw galacto-oligosaccharide purification by consecutive lactose hydrolysis and selective bioconversion. International Dairy Journal. 2017;75:91-100. https://doi.org/10.1016/j.idairyj.2017.07.008
- Guerrero C, Vera C, Illanes A. Selective bioconversion with yeast for the purifcation of raw lactulose and trans-galactosylated oligosaccharides. International Dairy Journal. 2018;81:131-137. https://doi.org/10.1016/j.idairyj.2018.02.003
- Srivastava A, Mishra S. Enrichment and evaluation of galactooligosaccharides produced by whole cell treatment of sugar reaction mixture. Molecular Biology Reports. 2019;46:1181-1188. https://doi.org/10.1007/s11033-019-04585-1
- Pazmandi M, Kovacs Z, Balga E, Kovacs M, Maraz A. Production of high-purity galacto-oligosaccharides by depleting glucose and lactose from galacto-oligosaccharide syrup with yeasts. Yeast. 2020;37(9-10):515-530. https://doi.org/10.1002/yea.3507
- Zhang X, Yao C, Wang T, Zhao H, Zhang B. Production of high-purity galacto-oligosaccharides (GOS) by Lacto-bacillus-derived в-galactosidase. European Food Research and Technology. 2021;247:1501-1510. https://doi.org/10.1007/s00217-021-03727-9
- Li Z, Tian-Tian L, Aziz T, Min Z, Sarwar A, et al. Purification of galacto-oligosaccharide (GOS) by fermentation with Kluyveromyces lactis and interaction between GOS and casein under simulated acidic fermentation conditions. World Journal of Microbiology and Biotechnology. 2023;39(12):342. https://doi.org/10.1007/s11274-023-03791-1
- Cao L, Bultsma M, Wissing J, Gerhard BE, Ziegler M, et al. High purity galacto-oligosaccharides: Optimal process design and prebiotic effect. Bioactive Carbohydrates and Dietary Fibre. 2023;30:100387. https://doi.org/10.1016/j.bcdf.2023.100387