Abstract
Lactose-free dairy products are in great demand worldwide due to the high prevalence of lactose intolerance. To make lactose-free dairy products, commercially available β-galactosidase enzymes, also termed lactases, are used to break down lactose to its constituent monosaccharides, glucose and galactose. In this mini-review, the characteristics of lactase enzymes, their origin, and ways of use are discussed in light of their potential for hydrolyzing lactose. We also discuss whole-cell lactase catalysts, which appear to have great potential in terms of cost reduction and convenience, and which are more natural alternatives to purified enzymes. Lactic acid bacteria (LAB) already used in food fermentations seem to be optimal candidates for whole-cell lactases. However, they have not been industrially exploited yet due to technical hurdles. For whole-cell lactases to be efficient, the lactase enzymes inside the cells must be made available for lactose hydrolysis, and thus, cells need to be permeabilized or disrupted prior to use. Here we review state-of-the-art approaches for disrupting or permeabilizing microorganisms. Lastly, based on recent scientific achievements, we propose a novel, resource-efficient, and low-cost scenario for achieving lactose hydrolysis at a dairy plant using a LAB whole-cell lactase.
Key points
• Lactases (β-galactosidase) are essential for producing lactose-free dairy products
• Novel permeabilization techniques facilitate the use of LAB lactases
• Whole-cell lactase catalysts have great potential for reducing costs and resources
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abesinghe AMNL, Islam N, Vidanarachchi JK, Prakash S, Silva KFST, Karim MA (2019) Effects of ultrasound on the fermentation profile of fermented milk products incorporated with lactic acid bacteria. Int Dairy J 90:1–14. https://doi.org/10.1016/j.idairyj.2018.10.006
Ansari SA, Satar R (2012) Recombinant β-galactosidases - past, present and future: a mini review. J Mol Catal B Enzym 81:1–6. https://doi.org/10.1016/j.molcatb.2012.04.012
Baret JC, Miller OJ, Taly V, Ryckelynck M, El-Harrak A, Frenz L, Rick C, Samuels ML, Hutchison JB, Agresti JJ, Link DR, Weitz DA, Griffiths AD (2009) Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. Lab Chip 9:1850–1858. https://doi.org/10.1039/b902504a
Benavente R, Pessela BC, Curiel JA, De Las RB, Muñoz R, Guisán JM, Mancheño JM, Cardelle-Cobas A, Ruiz-Matute AI, Corzo N (2015) Improving properties of a novel β-galactosidase from Lactobacillus plantarum by covalent immobilization. Molecules 20:7874–7889. https://doi.org/10.3390/molecules20057874
Bosso A, Morioka LRI, dos Santos LF, Suguimoto HH (2016) Lactose hydrolysis potential and thermal stability of commercial β-galactosidase in UHT and skimmed milk. Food Sci Technol 36:159–165. https://doi.org/10.1590/1678-457X.0085
Bunthof CJ, Van Schalkwijk S, Meijer W, Abee T, Hugenholtz J (2001) Fluorescent method for monitoring cheese starter permeabilization and lysis. Appl Environ Microbiol 67:4264–4271. https://doi.org/10.1128/AEM.67.9.4264-4271.2001
Chen J, Vestergaard M, Shen J, Solem C, Dufva M, Jensen PR (2018) Droplet-based microfluidics as a future tool for strain improvement in lactic acid bacteria. FEMS Microbiol Lett 365:1–7. https://doi.org/10.1093/femsle/fny258
Coker JA, Brenchley JE (2006) Protein engineering of a cold-active β-galactosidase from Arthrobacter sp. SB to increase lactose hydrolysis reveals new sites affecting low temperature activity. Extremophiles 10:515–524. https://doi.org/10.1007/s00792-006-0526-z
Dahlqvist A, Asp NG, Burvall A, Rausing H (1977) Hydrolysis of lactose in milk and whey with minute amounts of lactase. J Dairy Res 44:541–548. https://doi.org/10.1017/S0022029900020495
David S, Simons G, De Vos WM (1989) Plasmid transformation by electroporation of Leuconostoc paramesenteroides and its use in molecular cloning. Appl Environ Microbiol 55:1483–1489. https://doi.org/10.1128/aem.55.6.1483-1489.1989
de Andrade BC, Timmers LFSM, Renard G, Volpato G, de Souza CFV (2020) Microbial β-galactosidases of industrial importance: computational studies on the effects of point mutations on the lactose hydrolysis reaction. Biotechnol Prog 36:1–9. https://doi.org/10.1002/btpr.2982
DeCastro M-E, Escuder-Rodriguez J-J, Cerdan M-E, Becerra M, Rodriguez-Belmonte E, Gonzalez-Siso M-I (2018) Heat-loving β-galactosidases from cultured and uncultured microorganisms. Curr Protein Pept Sci 19:1224–1234. https://doi.org/10.2174/1389203719666180809111659
Decleire M, De Cat W, Van Huynh N (1987) Comparison of various permeabilization treatments on Kluyveromyces by determining in situ β-galactosidase activity. Enzym Microb Technol 9:300–302. https://doi.org/10.1016/0141-0229(87)90008-1
Dekker PJT, Daamen CBG (2011) Enzymes exogenous to milk in dairy technology: β-d-galactosidase. IN: Fuquay JW (ed) Encyclopedia of Dairy Sciences, 2nd Editio. Elsevier Ltd., pp 276–283
Dekker PJT, Koenders D, Bruins MJ (2019) Lactose-free dairy products: market developments, production, nutrition and health benefits. Nutrients 11:1–14. https://doi.org/10.3390/nu11030551
Dong YN, Liu XM, Chen HQ, Xia Y, Zhang HP, Zhang H, Chen W (2011) Enhancement of the hydrolysis activity of β-galactosidase from Geobacillus stearothermophilus by saturation mutagenesis. J Dairy Sci 94:1176–1184. https://doi.org/10.3168/jds.2010-3775
Dong YN, Wang L, Gu Q, Chen H, Liu X, Song Y, Chen W, Hagler AT, Zhang H, Xu J (2013) Optimizing lactose hydrolysis by computer-guided modification of the catalytic site of a wild-type enzyme. Mol Divers 17:371–382. https://doi.org/10.1007/s11030-013-9437-y
Dong Q, Yan X, Zheng M, Yang Z (2014) Characterization of an extremely thermostable but cold-adaptive β-galactosidase from the hyperthermophilic archaeon Pyrococcus furiosus for use as a recombinant aggregation for batch lactose degradation at high temperature. J Biosci Bioeng 117:706–710. https://doi.org/10.1016/j.jbiosc.2013.12.002
Facioni MS, Raspini B, Pivari F, Dogliotti E, Cena H, Cena H (2020) Nutritional management of lactose intolerance: the importance of diet and food labelling. J Transl Med 18:1–9. https://doi.org/10.1186/s12967-020-02429-2
Flores MV, Voget CE, Ertola RJJ (1994) Permeabilization of yeast cells (Kluyveromyces lactis) with organic solvents. Enzym Microb Technol 16:340–346. https://doi.org/10.1016/0141-0229(94)90177-5
Food and Drug Administration (FDA) (1978) Code of Federal Regulations (CFR), Title 21, Vol. 3, §184.1560, Ox bile extract
Food and Drug Administration (FDA) (1988) Code of Federal Regulations (CFR), Title 21, Vol. 3, §184.1538, Nisin Preparation
Geciova J, Bury D, Jelen P (2002) Methods for disruption of microbial cells for potential use in the dairy industry - a review. Int Dairy J 12:541–553. https://doi.org/10.1016/S0958-6946(02)00038-9
Genari AN, Passos FV, Passos FML (2003) Configuration of a bioreactor for milk lactose hydrolysis. J Dairy Sci 86:2783–2789. https://doi.org/10.3168/jds.S0022-0302(03)73875-2
Greenberg NA, Mahoney RR (1982) Production and characterization of β-galactosidase from Streptococcus thermophilus. J Food Sci 47:1824–1835. https://doi.org/10.1111/j.1365-2621.1982.tb12891.x
Greenberg NA, Mahoney RR (1984) The activity of lactase (Streptococcus thermophilus) in milk and sweet whey. Food Chem 15:307–313. https://doi.org/10.1016/0308-8146(84)90114-6
Guimarães JT, Balthazar CF, Scudino H, Pimentel TC, Esmerino EA, Ashokkumar M, Freitas MQ, Cruz AG (2019) High-intensity ultrasound: a novel technology for the development of probiotic and prebiotic dairy products. Ultrason Sonochem 57:12–21. https://doi.org/10.1016/j.ultsonch.2019.05.004
Gyawali R, Oyeniran A, Zimmerman T, Aljaloud SO, Krastanov A, Ibrahim SA (2020) A comparative study of extraction techniques for maximum recovery of β-galactosidase from the yogurt bacterium Lactobacillus delbrueckii ssp. bulgaricus. J Dairy Res 87:123–126. https://doi.org/10.1017/S0022029919001031
Hanne Vang, Hendrikson, Ernst S, Wilting R, Tams JW, Runge MO, Guldager HS (2010) Method for producing a dairy product. WO 2009/071539 A1.
Harju M, Kallioinen H, Tossavainen O (2012) Lactose hydrolysis and other conversions in dairy products: technological aspects. Int Dairy J 22:104–109. https://doi.org/10.1016/j.idairyj.2011.09.011
Horner TW, Dunn ML, Eggett DL, Ogden LV (2011) β-Galactosidase activity of commercial lactase samples in raw and pasteurized milk at refrigerated temperatures. J Dairy Sci 94:3242–3249. https://doi.org/10.3168/jds.2010-3742
Hoyoux A, Jennes I, Dubois P, Genicot S, Dubail F, François JM, Baise E, Feller G, Gerday C (2001) Cold-adapted β-galactosidase from the antarctic psychrophile Pseudoalteromonas haloplanktis. Appl Environ Microbiol 67:1529–1535. https://doi.org/10.1128/AEM.67.4.1529-1535.2001
Hu X, Robin S, O’Connell S, Walsh G, Wall JG (2010) Engineering of a fungal β-galactosidase to remove product inhibition by galactose. Appl Microbiol Biotechnol 87:1773–1782. https://doi.org/10.1007/s00253-010-2662-8
Ibrahim SA, O’Sullivan DJ (2000) Use of chemical mutagenesis for the isolation of food grade β-galactosidase overproducing mutants of bifidobacteria, lactobacilli and Streptococcus thermophilus. J Dairy Sci 83:923–930. https://doi.org/10.3168/jds.S0022-0302(00)74955-1
Iskandar CF, Cailliez-Grimal C, Borges F, Revol-Junelles AM (2019) Review of lactose and galactose metabolism in lactic acid bacteria dedicated to expert genomic annotation. Trends Food Sci Technol 88:121–132. https://doi.org/10.1016/j.tifs.2019.03.020
Joshi MS, Gowda LR, Bhat SG (1987) Permeabilization of yeast cells (KIuyveromyces fragilis) to lactose by cetyltrimethylammonium bromide. Biotechnol Lett 9:549–554
Joshi MS, Gowda LR, Katwa LC, Bhat SG (1989) Permeabilization of yeast cells (Kluyveromyces fragilis) to lactose by digitonin. Enzym Microb Technol 11:439–443. https://doi.org/10.1016/0141-0229(89)90140-3
Kolars JC, Levitt MD, Aouji M, Savaiano DA (1984) Yogurt — an autodigesting source of lactose. N Engl J Med 310:1–3. https://doi.org/10.1056/NEJM198401053100101
Kosseva MR, Panesar PS, Kaur G, Kennedy JF (2009) Use of immobilised biocatalysts in the processing of cheese whey. Int J Biol Macromol 45:437–447. https://doi.org/10.1016/j.ijbiomac.2009.09.005
Kourkoutas Y, Bekatorou A, Banat IM, Marchant R, Koutinas AA (2004) Immobilization technologies and support materials suitable in alcohol beverages production: a review. Food Microbiol 21:377–397. https://doi.org/10.1016/j.fm.2003.10.005
Lim J, Vrignon J, Gruner P, Karamitros CS, Konrad M, Baret JC (2013) Ultra-high throughput detection of single cell β-galactosidase activity in droplets using micro-optical lens array. Appl Phys Lett 103:1–4. https://doi.org/10.1063/1.4830046
Liu JM, Chen L, Dorau R, Lillevang SK, Jensen PR, Solem C (2020) From waste to taste - efficient production of the butter aroma compound acetoin from low-value dairy side streams using a natural (nonengineered) Lactococcus lactis dairy isolate. J Agric Food Chem 68:5891–5899. https://doi.org/10.1021/acs.jafc.0c00882
Lomer MCE, Parkes GC, Sanderson JD (2008) Review article: Lactose intolerance in clinical practice - myths and realities. Aliment Pharmacol Ther 27:93–103. https://doi.org/10.1111/j.1365-2036.2007.03557.x
Mastrobattista E, Taly V, Chanudet E, Treacy P, Kelly BT, Griffiths AD (2005) High-throughput screening of enzyme libraries: in vitro evolution of a β-galactosidase by fluorescence-activated sorting of double emulsions. Chem Biol 12:1291–1300. https://doi.org/10.1016/j.chembiol.2005.09.016
Mateo C, Monti R, Pessela BCC, Fuentes M, Torres R, Guisán JM, Fernández-Lafuente R (2004) Immobilization of lactase from Kluyveromyces lactis greatly reduces the inhibition promoted by glucose. full hydrolysis of lactose in milk. Biotechnol Prog 20:1259–1262
Matthews SB, Waud JP, Roberts AG, Campbell AK (2005) Systemic lactose intolerance: a new perspective on an old problem. Postgrad Med J 81:167–173. https://doi.org/10.1136/pgmj.2004.025551
McCain HR, Kaliappan S, Drake MA (2018) Invited review: sugar reduction in dairy products. J Dairy Sci 101:8619–8640. https://doi.org/10.3168/jds.2017-14347
Moll GN, Konings WN, Driessen AJM (1999) Bacteriocins: mechanism of membrane insertion and pore formation. Antonie Van Leeuwenhoek 76:185–198. https://doi.org/10.1023/A:1002002718501
Morioka LRI, de Colognesi GO, Suguimoto HH (2016) Permeabilization of Saccharomyces fragilis IZ 275 cells with ethanol to obtain a biocatalyst with lactose hydrolysis capacity. Acta Sci - Biol Sci 38:149–155. https://doi.org/10.4025/actascibiolsci.v38i2.29220
Morioka LRI, Viana CDS, de Alves ÉP, Paião FG, Takihara AM, ASS K, Suguimoto HH (2019) Concentrated beta-galactosidase and cell permeabilization from Saccharomyces fragilis IZ 275 for beta-galactosidase activity in the hydrolysis of lactose. Food Sci Technol 39:524–530. https://doi.org/10.1590/fst.06017
Morisi F, Pastore M, Viglia A (1973) Reduction of lactose content of milk by entrapped β-galactosidase. I. characteristics of β-galactosidase from yeast and Escherichia coli. J Dairy Sci 56:1123–1127. https://doi.org/10.3168/jds.S0022-0302(73)85320-2
Mota MJ, Lopes RP, Koubaa M, Roohinejad S, Barba FJ, Delgadillo I, Saraiva JA (2018) Fermentation at non-conventional conditions in food- and bio-sciences by the application of advanced processing technologies. Crit Rev Biotechnol 38:122–140. https://doi.org/10.1080/07388551.2017.1312272
Nakagawa T, Fujimoto Y, Uchino M, Miyaji T, Takano K, Tomizuka N (2003) Isolation and characterization of psychrophiles producing cold-active β-galactosidase. Lett Appl Microbiol 37:154–157. https://doi.org/10.1046/j.1472-765X.2003.01369.x
Nakagawa T, Ikehata R, Uchino M, Miyaji T, Takano K, Tomizuka N (2006) Cold-active acid β-galactosidase activity of isolated psychrophilic-basidiomycetous yeast Guehomyces pullulans. Microbiol Res 161:75–79. https://doi.org/10.1016/j.micres.2005.07.003
Nguyen TMP, Lee YK, Zhou W (2009) Stimulating fermentative activities of bifidobacteria in milk by highintensity ultrasound. Int Dairy J 19:410–416. https://doi.org/10.1016/j.idairyj.2009.02.004
Nguyen TMP, Lee YK, Zhou W (2012) Effect of high intensity ultrasound on carbohydrate metabolism of bifidobacteria in milk fermentation. Food Chem 130:866–874. https://doi.org/10.1016/j.foodchem.2011.07.108
Nolan GP, Fiering S, Nicholas J-F, Herzenberg LA (1988) Fluorescence-activated cell analysis and sorting of viable mammalian cells based on beta-galactosidase activity after transduction of Escherichia coli lacZ. Proc Natl Acad Sci 85:2603–2607. https://doi.org/10.1073/pnas.85.8.2603
Ojha KS, Mason TJ, O’Donnell CP, Kerry JP, Tiwari BK (2017) Ultrasound technology for food fermentation applications. Ultrason Sonochem 34:410–417. https://doi.org/10.1016/j.ultsonch.2016.06.001
Panesar PS, Panesar R, Singh RS, Kennedy JF, Kumar H (2006) Microbial production, immobilization and applications of β-D-galactosidase. J Chem Technol Biotechnol 81:530–543. https://doi.org/10.1002/jctb.1453
Panesar R, Panesar PS, Singh RS, Kennedy JF, Bera MB (2007) Production of lactose-hydrolyzed milk using ethanol permeabilized yeast cells. Food Chem 101:786–790. https://doi.org/10.1016/j.foodchem.2006.02.064
Pastore M, Morisi F (1976) Lactose reduction of milk by fiber-entrapped β-galactosidase. pilot-plant experiments. Methods Enzymol 44:822–830. https://doi.org/10.1016/S0076-6879(76)44059-4
Pastore M, Morisi F (1978) Reduction of lactose in milk by entrapped β-galactosidase IV. Results of long term experiments with a pilot plant. In: Kendall Pye E, Weetall HH (eds) Enzyme Engineering. Springer US, pp 537–542
Pastore M, Morisi F, Viglia A (1974) Reduction of lactose of Milk by entrapped β-galactosidase. II. Conditions for an Industrial Continuous Process. J Dairy Sci 57:269–272. https://doi.org/10.3168/jds.S0022-0302(74)84875-7
Pavani A, Prabhakar T, Girija Sankar G, Kamala Kumari PV (2009) Strain improvement studies of Aspergillus flavus for enhanced β-galactosidase production. J Pure Appl Microbiol 3:279–284
Peralta GH, Bergamini CV, Hynes ER (2019) Disruption treatments on two strains of Streptococcus thermophilus: Levels of lysis/permeabilisation of the cultures and influence of treated cultures on the ripening profiles of Cremoso cheese. Int Dairy J 92:11–20. https://doi.org/10.1016/j.idairyj.2019.01.002
Petzelbauer I, Kuhn B, Splechtna B, Kulbe KD, Nidetzky B (1999) Development of an ultrahigh-temperature process for the enzymatic hydrolysis of lactose. I. The properties of two thermostable β-glycosidases. Biotechnol Bioeng 64:322–332. https://doi.org/10.1002/bit.10110
Petzelbauer I, Zeleny R, Reiter A, Kulbe KD, Nidetzky B (2000) Development of an ultrahigh-temperature process for the enzymatic hydrolysis of lactose. II. Oligosaccharide Formation by Two Thermostable β-Glycosidases. Biotechnol Bioeng 69:140–149. https://doi.org/10.1002/bit.10110
Petzelbauer I, Kuhn B, Splechtna B, Kulbe KD, Nidetzky B (2002a) Development of an ultrahigh-temperature process for the enzymatic hydrolysis of lactose. IV. Immobilization of two thermostable β-glycosidases and optimization of a packed-bed reactor for lactose conversion. Biotechnol Bioeng 77:619–631. https://doi.org/10.1002/bit.10110
Petzelbauer I, Splechtna B, Nidetzky B (2002b) Development of an ultrahigh-temperature process for the enzymatic hydrolysis of lactose. III. Utilization of two thermostable β-glycosidases in a continuous ultrafiltration membrane reactor and galacto-oligosaccharide formation under steady-state conditio. Biotechnol Bioeng 77:394–404. https://doi.org/10.1002/bit.10106
Pulicherla KK, Kumar PS, Manideep K, Rekha VPB, Ghosh M, Rao KRSS (2013) Statistical approach for the enhanced production of cold- active β-galactosidase from Thalassospira frigidphilosprofundus: a novel marine psychrophile from deep water of bay of bengal. Prep Biochem Biotechnol 43:766–780. https://doi.org/10.1080/10826068.2013.773341
Ramana Rao MV, Dutta SM (1977) Production of beta-galactosidase from Streptococcus thermophilus grown in whey. Appl Environ Microbiol 34:185–188. https://doi.org/10.1128/aem.34.2.185-188.1977
Ramana Rao MV, Dutta SM (1978) Lactase activity of microorganisms. Folia Microbiol (Praha) 23:210–215. https://doi.org/10.1007/BF02876581
Raol GG, Raol BV, Pandya PD (2010) Improved production of β-galactosidase from the mutated Aspergillus sp. on deproteinized cheese whey. Nat Environ Pollut Technol 9:699–705
Rentschler E, Schwarz T, Stressler T, Fischer L (2016) Development and validation of a screening system for a β-galactosidase with increased specific activity produced by directed evolution. Eur Food Res Technol 242:2129–2138. https://doi.org/10.1007/s00217-016-2709-x
Rico-Díaz A, Álvarez-Cao ME, Escuder-Rodríguez JJ, González-Siso MI, Cerdán ME, Becerra M (2017) Rational mutagenesis by engineering disulphide bonds improves Kluyveromyces lactis beta-galactosidase for high-temperature industrial applications. Sci Rep 7:1–11. https://doi.org/10.1038/srep45535
Sakakibara M, Wang D, Ikeda K, Suzuki K (1994) Effect of ultrasonic irradiation on production of fermented milk with Lactobacillus delbrueckii. Ultrason Sonochem 1:107–110. https://doi.org/10.1016/b0-12-227235-8/00243-1
Saqib S, Akram A, Halim SA, Tassaduq R (2017) Sources of β-galactosidase and its applications in food industry. 3. Biotech 7:1–7. https://doi.org/10.1007/s13205-017-0645-5
Sasaki Y, Horiuchi H, Kawashima H, Mukai T, Yamamoto Y (2014) NADH oxidase of Streptococcus thermophilus 1131 is required for the effective yogurt fermentation with Lactobacillus delbrueckii subsp. bulgaricus 2038. Biosci Microbiota, Food Heal 33:31–40. https://doi.org/10.12938/bmfh.33.31
Savaiano DA (2014) Lactose digestion from yogurt: mechanism and relevance. Am J Clin Nutr 99:1251–1255. https://doi.org/10.3945/ajcn.113.073023
Shah N, Jelen P (1990) Survival of lactic acid bacteria and their lactases under acidic conditions. J Food Sci 55:506–509. https://doi.org/10.1111/j.1365-2621.1990.tb06797.x
Shah NO, Nickerson TA (1978) Functional properties of hydrolyzed lactose: relative sweetness. J Food Sci 43:1575–1576. https://doi.org/10.1111/j.1365-2621.1978.tb15238.x
Silanikove N, Leitner G, Merin U (2015) The interrelationships between lactose intolerance and the modern dairy industry: global perspectives in evolutional and historical backgrounds. Nutrients 7:7312–7331. https://doi.org/10.3390/nu7095340
Somkuti GA, Steinberg DH (1994) Permeabilization of Streptococcus thermophilus and the expression of beta-galactosidase. Enzym Microb Technol 16:573–576. https://doi.org/10.1016/0141-0229(94)90121-X
Somkuti GA, Dominiecki ME, Steinberg DH (1998) Permeabilization of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus with Ethanol. Curr Microbiol 36:202–206. https://doi.org/10.1007/s002849900294
Teraguchi S, Ono J, Kiyosawa I, Okonogi S (1987) Oxygen uptake activity and aerobic metabolism of Streptococcus thermophilus STH450. J Dairy Sci 70:514–523. https://doi.org/10.3168/jds.S0022-0302(87)80036-X
Toba T, Hayasaka I, Taguchi S, Adachi S (1990) A new method for manufacture of lactose-hydrolysed fermented milk. J Sci Food Agric 52:403–407. https://doi.org/10.1002/jsfa.2740520313
Troise AD, Bandini E, De Donno R, Meijer G, Trezzi M, Fogliano V (2016) The quality of low lactose milk is affected by the side proteolytic activity of the lactase used in the production process. Food Res Int 89:514–525. https://doi.org/10.1016/j.foodres.2016.08.021
Ureta MM, Martins GN, Figueira O, Pires PF, Castilho PC, Gomez-Zavaglia A (2020) Recent advances in β-galactosidase and fructosyltransferase immobilization technology. Crit Rev Food Sci Nutr1–32. doi: https://doi.org/10.1080/10408398.2020.1783639
Van Dam B, Revallier-Warffemius JG, Dam-Schermerhorn LCV (1950) Preparation of lactase from Saccharomyces fragilis. Ned Melk- en Zuiveltijdschr 4:96–114
Vasiljevic T, Jelen P (2001) Production of β-galactosidase for lactose hydrolysis in milk and dairy products using thermophilic lactic acid bacteria. Innov Food Sci Emerg Technol 2:75–85. https://doi.org/10.1016/S1466-8564(01)00027-3
Vasiljevic T, Jelen P (2003) Oligosaccharide production and proteolysis during lactose hydrolysis using crude cellular extracts from lactic acid bacteria. Lait 83:453–467. https://doi.org/10.1051/lait:2003025
Vincent V, Aghajari N, Pollet N, Boisson A, Boudebbouze S, Rhimi RH, Maguin E, Rhimi M (2013) The acid tolerant and cold-active galactosidase from Lactococcus lactis strain is an attractive biocatalyst for lactose hydrolysis. Antonie Van Leeuwenhoek 103:701–712. https://doi.org/10.1007/s10482-012-9852-6
Vlach D, Prenosil JE (1984) Yeast cells with high beta-galactosidase activity and their immobilization. J Mol Catal 26:173–185. https://doi.org/10.1016/0304-5102(84)85001-4
VLOG - Verband Lebensmittel ohne Gentechnik e.V. https://www.ohnegentechnik.org/. Accessed 23 Dec 2020
Wang D, Sakakibara M (1997) Lactose hydrolysis and β-galactosidase activity in sonicated fermentation with Lactobacillus strains. Ultrason Sonochem 4:255–261. https://doi.org/10.1016/S1350-4177(96)00042-9
Wang D, Sakakibara M, Kondoh N, Suzuki K (1996) Ultrasound-enhanced lactose hydrolysis in milk fermentation with Lactobacillus bulgaricus. J Chem Technol Biotechnol 65:86–92. https://doi.org/10.1002/(SICI)1097-4660(199601)65:1<86::AID-JCTB394>3.0.CO;2-L
Wang Q, Lillevang SK, Rydtoft SM, Xiao H, Fan M, Solem C, Liu J, Jensen PR (2020) No more cleaning up - efficient lactic acid bacteria cell catalysts as a cost-efficient alternative to purified lactase enzymes. Appl Microbiol Biotechnol 104:6315–6323. https://doi.org/10.1007/s00253-020-10655-3
Wierzbicki LE, Kosikowski FV (1973) Lactase potential of various microorganisms grown in whey. J Dairy Sci 56:26–32. https://doi.org/10.3168/jds.S0022-0302(73)85110-0
Willett WC, Ludwig DS (2020) Milk and health. N Engl J Med 382:644–654. https://doi.org/10.1056/NEJMra1903547
Woodley JM (2020) Advances in biological conversion technologies: new opportunities for reaction engineering. React Chem Eng 5:632–640. https://doi.org/10.1039/c9re00422j
Yu L, O’Sullivan DJ (2018) Immobilization of whole cells of Lactococcus lactis containing high levels of a hyperthermostable β-galactosidase enzyme in chitosan beads for efficient galacto-oligosaccharide production. J Dairy Sci 101:1–10. https://doi.org/10.3168/jds.2017-13770
Zendo T, Yoneyama F, Sonomoto K (2010) Lactococcal membrane-permeabilizing antimicrobial peptides. Appl Microbiol Biotechnol 88:1–9. https://doi.org/10.1007/s00253-010-2764-3
Zhang W, Liu F, Yang M, Liang Q, Zhang Y, Ai D, An Z (2014) Enhanced β-galactosidase production of Aspergillus oryzae mutated by UV and LiCl. Prep Biochem Biotechnol 44:310–320. https://doi.org/10.1080/10826068.2013.829496
Zhang Z, Zhang F, Song L, Sun N, Guan W, Liu B, Tian J, Zhang Y, Zhang W (2018) Site-directed mutation of β-galactosidase from Aspergillus candidus to reduce galactose inhibition in lactose hydrolysis. 3 Biotech 8:1–7. https://doi.org/10.1007/s13205-018-1418-5
Zhao G, Liu J, Zhao J, Dorau R, Jensen PR, Solem C (2021) Efficient production of nisin a from low-value dairy side streams using a nonengineered dairy Lactococcus lactis with low lactate dehydrogenase activity. J Agric Food Chem
Availability of data and material
Not applicable.
Code availability
Not applicable.
Funding
This work was supported by the Innovation Fund Denmark (Grant No. 6150-00036B), DTU PoC Fund (“Sweet as Sugar”), and a grant from ARLA Foods.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. RD and CS performed the literature search and data analysis. RD wrote the first draft of the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors have filed a patent application (European Patent Application No. 20157131.2) regarding the use of nisin as a food-grade permeabilization agent for gram-positive bacteria and its application for producing lactose-free dairy products with whole-cell lactase catalysts.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Dorau, R., Jensen, P.R. & Solem, C. Purified lactases versus whole-cell lactases—the winner takes it all. Appl Microbiol Biotechnol 105, 4943–4955 (2021). https://doi.org/10.1007/s00253-021-11388-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-021-11388-7