Yeast cell factories for sustainable whey-to-ethanol valorisation towards a circular economy

Document Type : Review Paper

Authors

Centre of Biological Engineering, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.

Abstract

Cheese whey is the major by-product of the dairy industry, and its disposal constitutes an environmental concern. The production of cheese whey has been increasing, with 190 million tonnes per year being produced nowadays. Therefore, it is emergent to consider different routes for cheese whey utilization. The great nutritional value of cheese whey turns it into an attractive substrate for biotechnological applications. Currently, cheese whey processing includes a protein fractionating step that originates the permeate, a lactose-reach stream further used for valorisation.  In the last decades, yeast fermentation has brought several advances to the search for biorefinery alternatives. From the plethora of value-added products that can be obtained from cheese whey, ethanol is the most extensively explored since it is the alternative biofuel most used worldwide. Thus, this review focuses on the different strategies for ethanol production from cheese whey using yeasts as promising biological systems, including its integration in lignocellulosic biorefineries. These valorisation routes encompass the improvement of the fermentation process as well as metabolic engineering techniques for the introduction of heterologous pathways, resorting mainly to Kluyveromyces sp. and Saccharomyces cerevisiae strains. The solutions and challenges of the several strategies will be unveiled and explored in this review.

Graphical Abstract

Yeast cell factories for sustainable whey-to-ethanol valorisation towards a circular economy

Highlights

  • Whey is the major by-product of the dairy industry, being an environmental concern.
  • Bioethanol is the prevalent product obtained from cheese whey fermentation.
  • Kluyveromyces sp. and Saccharomyces cerevisiae are the most used hosts for whey valorisation.
  • Novel valorisation routes are rising due to the advances in metabolic engineering.
  • Integration of multi-valorisation pathways will positively impact process economics.

Keywords


  1. Abdel-Banat, B.M.A., Hoshida, H., Ano, A., Nonklang, S., Akada, R., 2010. High-temperature fermentation: how can processes for ethanol production at high temperatures become superior to the traditional process using mesophilic yeast?. Appl. Microbiol. Biotechnol. 85(4), 861-867.
  2. Abou-Zeid, A.Z.A., Baghlaf, A.O., Khan, J.A., Makhashin, S.S., 1983. Utilization of date seeds and cheese whey in production of citric acid by Candida lipolytica. Agric. Wastes. 8(3), 131-142.
  3. Addai, F.P., Lin, F., Wang, T., Kosiba, A.A., Sheng, P., Yu, F., Gu, J., Zhou, Y., Shi, H., 2020. Technical integrative approaches to cheese whey valorization towards sustainable environment. Food Funct. 11(10), 8407-8423.
  4. Aguilera, F., Peinado, R.A., Millán, C., Ortega, J.M., Mauricio, J.C., 2006. Relationship between ethanol tolerance, H+-ATPase activity and the lipid composition  of the  plasma  membrane  in different wine yeast strains. Int. J. Food Microbiol. 110(1), 34-42.
  5. Álvarez-Cao, M.E., Becerra, M., González-Siso, M.I., 2020. Biovalorization of cheese whey and molasses wastes to galactosidases by recombinant yeasts, in: Biovalorisation of Wastes to Renewable Chemicals and Biofuels. Elsevier, pp. 149-161.
  6. Andrade, R.P., Melo, C.N., Genisheva, Z., Schwan, R.F., Duarte, W.F., 2017. Yeasts from Canastra cheese production process: isolation and evaluation of their potential for cheese whey fermentation. Food Res. Int. 91, 72-79.
  7. Arous, F., Frikha, F., Triantaphyllidou, I.E., Aggelis, G., Nasri, M., Mechichi, T., 2016. Potential utilization of agro-industrial wastewaters for lipid production by the oleaginous yeast Debaryomyces etchellsii. J. Clean. Prod. 133, 899-909.
  8. Arous, F., Atitallah, I. Ben, Nasri, M., Mechichi, T., 2017. A sustainable use of low-cost raw substrates for biodiesel production by the oleaginous yeast Wickerhamomyces anomalus. 3 Biotech, 7(4), pp. 1-10.
  9. Arslan, N.P., Aydogan, M.N., Taskin, M., 2016. Citric acid production from partly deproteinized whey under non-sterile culture conditions using immobilized cells of lactose-positive and cold-adapted Yarrowia lipolytica J. Biotechnol. 231, 32-39.
  10. Asunis, F., De Gioannis, G., Dessì, P., Isipato, M., Lens, P.N., Muntoni, A., Polettini, A., Pomi, R., Rossi, A., Spiga, D., 2020. The dairy biorefinery: integrating treatment processes for cheese whey valorisation. J. Environ. Manage. 276, 111240.
  11. Audic, J.L., Chaufer, B., Daufin, G., 2003. Non-food applications of milk components and dairy co-products: a review. Le Lait. 83(6), 417-438.
  12. Bailey, R.B., Benitez, T., Woodward, A., 1982. Saccharomyces cerevisiae mutants resistant to catabolite repression: use in cheese whey hydrolysate fermentation. Appl. Environ. Microbiol. 44(3), 631-639.
  13. Balat, M., 2011. Production of bioethanol from lignocellulosic materials via the biochemical pathway: a review. Energy Convers. Manage. 52(2), 858-875.
  14. Bansal, S., Oberoi, H.S., Dhillon, G.S., Patil, R.T., 2008. Production of β-galactosidase by Kluyveromyces marxianus MTCC 1388 using whey and effect of four different methods of enzyme extraction on β-galactosidase activity. Indian J. Microbiol. 48(3), 337-341.
  15. Baptista, S.L., Costa, C.E., Cunha, J.T., Soares, P.O., Domingues, L., 2021. Metabolic engineering of Saccharomyces cerevisiae for the production of top value chemicals from biorefinery carbohydrates. Biotechnol. Adv. 47, 107697.
  16. Barile, D., Tao, N., Lebrilla, C.B., Coisson, J.D., Arlorio, M., German, J.B., 2009. Permeate from cheese whey ultrafiltration is a source of milk oligosaccharides. Dairy J. 19(9), 524-530.
  17. Becerra, M., Prado, S.D., Cerdán, E., Siso, M.G., 2001a. Heterologous Kluyveromyces lactis β-galactosidase secretion by Saccharomyces cerevisiae super-secreting mutants. Biotechnol. Lett. 23(1), 33-40.
  18. Becerra, M., Prado, S.D., Siso, M.G., Cerdán, M.E., 2001b. New secretory strategies for Kluyveromyces lactis β-galactosidase. Protein Eng. 14(5), 379-386.
  19. Becerra, M., Rodríguez-Belmonte, E., Cerdán, M.E., González Siso, M.I.G., 2004. Engineered autolytic yeast strains secreting Kluyveromyces lactis β-galactosidase for production of heterologous proteins in lactose media. J. Biotechnol. 109(1-2), 131-137.
  20. Beniwal, A., Saini, P., Kokkiligadda, A., Vij, S., 2018. Use of silicon dioxide nanoparticles for β-galactosidase immobilization and modulated ethanol production by co-immobilized marxianus and S. cerevisiae in deproteinized cheese whey. LWT. 87, 553-561.
  21. Bosso, A., Setti, A.C.I., Tomal, A.B., Guemra, S., Morioka, L.R.I., Suguimoto, H.H., 2019. Substrate consumption and beta-galactosidase production by Saccharomyces fragilis IZ 275 grown in cheese whey as a function of cell growth rate. Biocatal. Agric. Biotechnol. 21, 101335.
  22. Boze, H., Mouhn, G., Galzu, P., 1987. Galactose and Lactose Transport in Kluyveromyces lactis. Folia Microbiol. 32(2), 107.
  23. Brandelli, A., Daroit, D.J., Corrêa, A.P.F., Whey as a source of peptides with remarkable biological activities. Food Res. Int. 73, 149-161.
  24. Breunig, K.D., Bolotin-Fukuhara, M., Bianchi, M.M., Bourgarel, D.., Falcone, C., Ferrero, I., Frontali, L., Goffrini, P., Krijger, J.J., Mazzoni, C., Milkowski, C., 2000. Regulation of primary carbon metabolism in Kluyveromyces lactis. Enzyme Microb. Technol. 26(9-10), 771-780.
  25. Carota, E., Crognale, S., D’Annibale, A., Gallo, A.M., Stazi, S.R., Petruccioli, M., 2017. A sustainable use of Ricotta Cheese Whey for microbial biodiesel production. Total Environ. 584-585, 554-560.
  26. Carranza-Saavedra, D., Henao, C.P.S., Montoya, J.E.Z., 2021. Kinetic analysis and modeling of L-valine production in fermentation batch from coli using glucose, lactose and whey as carbon sources. Biotechnol. Reports. 31, e00642.
  27. Carvalho, F., Prazeres, A.R., Rivas, J., 2013. Cheese whey wastewater: characterization and treatment. Total Environ. 445-446, 385-396.
  28. Castanha, R.F., Mariano, A.P., Morais, L.A.S.D., Scramin, S., Monteiro, R.T.R., 2014. Optimization of lipids production by Cryptococcus laurentii 11 using cheese whey with molasses. J. Microbiol. 45, 379-387.
  29. Castrillo, J.I., Kaliterna, J., Weusthuis, R.A., Van Dijken, J.P., Pronk, J.T., 1996. High-cell-density cultivation of yeasts on disaccharides in oxygen-limited batch cultures. Biotechnol. Bioeng. 49(6), 621-628.
  30. Castrillo, J.I., Ugalde, U.O., 1993. Patterns of energy metabolism and growth kinetics of Kluyveromyces marxianus in whey chemostat culture. Appl. Microbiol. Biotechnol. 40(2), 386-393.
  31. Champagne, C.P., Goulet, J., 1988. Growth of bakers’ yeast (Saccharomyces cerevisiae) in lactose-hydrolyzed cheese whey ultrafiltrate. Can. Inst. Food Sci. Technol. J. 21(5), 545-548.
  32. Christensen, A.D., Kádár, Z., Oleskowicz-Popiel, P., Thomsen, M.H., 2011. Production of bioethanol from organic whey using Kluyveromyces marxianus. J. Ind. Microbiol. Biotechnol. 38(2), 283-289.
  33. Compagno, C., Tura, A., Ranzi, B.M., Martegani, E., 1993. Bioconversion of lactose/whey to fructose diphosphate with recombinant Saccharomyces cerevisiae Biotechnol. Bioeng. 42(3), 398-400.
  34. Costa, C.E., Romaní, A., Cunha, J.T., Johansson, B., Domingues, L., 2017. Integrated approach for selecting efficient Saccharomyces cerevisiae for industrial lignocellulosic fermentations: importance of yeast chassis linked to process conditions. Bioresour. Technol. 227, 24-34.
  35. Costa, D.A., De Souza, C.J., Costa, P.S., Rodrigues, M.Q., Dos Santos, A.F., Lopes, M.R., Genier, H.L., Silveira, W.B., Fietto, L.G., 2014. Physiological characterization of thermotolerant yeast for cellulosic ethanol production. Appl. Biotechnol. 98(8), 3829-3840.
  36. Cunha, J.T., Romaní, A., Costa, C.E., Sá-Correia, I., Domingues, L., 2019. Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions. Appl. Microbiol. Biotechnol. 103(1), 159-175.
  37. Cunha, J.T., Soares, P.O., Baptista, S.L., Costa, C.E., Domingues, L., 2020. Engineered Saccharomyces cerevisiae for lignocellulosic valorization: a review and perspectives on bioethanol production. Bioengineered. 11(1), 883-903.
  38. Cunha, J.T., Gomes, D.G., Romaní, A., Inokuma, K., Hasunuma, T., Kondo, A., Domingues, L., 2021. Cell surface engineering of Saccharomyces cerevisiae for simultaneous valorization of corn cob and cheese whey via ethanol production. Energy Convers. Manage. 243, 114359.
  39. Cunha, M., Romaní, A., Carvalho, M., Domingues, L., 2018. Boosting bioethanol production from Eucalyptus wood by whey incorporation. Bioresour. Technol. 250, 256-264.
  40. D’Amato, D., Droste, N., Allen, B., Kettunen, M., Lähtinen, K., Korhonen, J., Leskinen, P., Matthies, B.D., Toppinen, A., 2017. Green, circular, bio economy: a comparative analysis of sustainability avenues. J. Clean. Prod. 168, 716-734.
  41. Daniel, H.J., Otto, R.T., Binder, M., Reuss, M., Syldatk, C., 1999. Production of sophorolipids from whey: development of a two-stage process with Cryptococcus curvatus ATCC 20509 and Candida bombicola ATCC 22214 using deproteinized whey concentrates as substrates. Appl. Microbiol. Biotechnol. 51(1), 40-45.
  42. Das, B., Sarkar, S., Maiti, S., Bhattacharjee, S., 2016. Studies on production of ethanol from cheese whey using Kluyveromyces marxianus. Mater. Today: Proc. 3(10), 3253-3257.
  43. De Felice, B., Blasi, V.O., de Castro, O., Cennamo, P., Martino, L., Trifuoggi, M., Condorelli, V., Di Onofrio, V., Guida, M., 2012. Genetic structure of a novel biofuel-producing microorganism community. J. Genet. 91(2), 183-191.
  44. de Freitas, M.D.F.M. de, Hortêncio, L.C., Albuquerque, T.L. de, Rocha, M.V.P., Gonçalves, L.R.B., 2020. Simultaneous hydrolysis of cheese whey and lactulose production catalyzed by β-galactosidase from Kluyveromyces lactis NRRL Y1564. Bioprocess. Biosyst. Eng. 43(4), 711-722.
  45. del Río, P.G., Gomes-Dias, J.S., Rocha, C.M., Romaní, A., Garrote, G., Domingues, L., 2020. Recent trends on seaweed fractionation for liquid biofuels production. Bioresour. Technol. 299, 122613.
  46. Demirel, B., Yenigun, O., Onay, T.T., 2005. Anaerobic treatment of dairy wastewaters: a review. Process Biochem. 40(8), 2583-2595.
  47. Díez-Antolínez, R., Hijosa-Valsero, M., Paniagua-García, A.I., Garita-Cambronero, J., Gómez, X., 2018. Yeast screening and cell immobilization on inert supports for ethanol production from cheese whey permeate with high lactose loads. PLoS One. 13(12), e0210002.
  48. Díez-Antolínez, R., Hijosa-Valsero, M., Paniagua A.I., Gómez, X., 2016. Very-high-gravity fermentation of non-supplemented cheese whey permeate by immobilized Kluyveromyces marxianus, in: Chemical Engineering Transactions. 49, pp. 529-534.
  49. Dinika, I., Utama, G.L., 2019. Cheese whey as potential resource for antimicrobial edible film and active packaging production. Foods Raw Mater. 7(2), 229-239.
  50. Dinika, I., Verma, D.K., Balia, R., Utama, G.L., Patel, A.R., 2020. Potential of cheese whey bioactive proteins and peptides in the development of antimicrobial edible film composite: a review of recent trends. Trends Food Sci. Technol. 103, 57-67.
  51. Diniz, R.H., Rodrigues, M.Q., Fietto, L.G., Passos, F.M., Silveira, W.B., 2014. Optimizing and validating the production of ethanol from cheese whey permeate by Kluyveromyces marxianus UFV-3. Agric. Biotechnol. 3(2), 111-117.
  52. Domingues, L., Teixeira, J.A., Lima, N., 1999a. Construction of a flocculent Saccharomyces cerevisiae fermenting lactose. Appl. Microbiol. Biotechnol. 51(5), 621-626.
  53. Domingues, Lucília, Dantas, M.M., Lima, N., Teixeira, J.A., 1999b. Continuous ethanol fermentation of lactose by a recombinant flocculating Saccharomyces cerevisiae Biotechnol. Bioeng. 64(6), 692-697.
  54. Domingues, L., Onnela, M.L., Teixera, J.A., Lima, N., Penttilä, M., 2000a. Construction of a flocculent brewer’s yeast strain secreting Aspergillus niger β-galactosidase. Appl. Microbiol. Biotechnol. 54(1), 97-103.
  55. Domingues, L, Vicente, A.A., Lima, N., Teixeira, J.A., 2000b. Applications of Yeast Flocculation in Biotechnological Processes. Biotechnol. Bioprocess Eng. 5(4), 288-305.
  56. Domingues, L., Lima, N., Teixeira, J.A., 2001. Alcohol production from cheese whey permeate using genetically modified flocculent yeast cells. Biotechnol. Bioeng. 72(5), 507-514.
  57. Domingues, L., Teixeira, J., Penttilä, M., Lima, N., 2002. Construction of a flocculent Saccharomyces cerevisiae strain secreting high levels of Aspergillus niger β-galactosidase. Appl. Microbiol. Biotechnol. 58(5), 645-650.
  58. Domingues, L., Lima, N., Teixeira, J.A., 2005. Aspergillus niger β-galactosidase production by yeast in a continuous high cell density reactor. Process Biochem. 40(3-4), 1151-1154.
  59. Domingues, L., Guimarães, P.M., Oliveira, C., 2010. Metabolic engineering of Saccharomyces cerevisiae for lactose/whey fermentation. Bioeng. Bugs. 1(3), 164-171.
  60. Donaghy, J.A., McKay, A.M., 1994. Pectin extraction from citrus peel by polygalacturonase produced on whey. Bioresour. Technol. 47(1), 25-28.
  61. Dragone, G., Mussatto, S.I., Oliveira, J.M., 2009. Characterisation of volatile compounds in an alcoholic beverage produced by whey fermentation. Food Chem. 112(4), 929-935.
  62. Dragone, G., Mussatto, S.I., e Silva, J.B.A., Teixeira, J.A., 2011. Optimal fermentation conditions for maximizing the ethanol production by Kluyveromyces fragilis from cheese whey powder. Biomass Bioenergy. 35(5), 1977-1982.
  63. Eş, I., Vieira, J.D.G., Amaral, A.C., 2015. Principles, techniques, and applications of biocatalyst immobilization for industrial application. Appl. Microbiol. Biotechnol. 99(5), 2065-2082.
  64. FAO, 2020. World milk production trends in 2018.
  65. Farahnak, F., Seki, T., Ryu, D.D.Y., Ogrydziak, D., 1986. Construction of lactose-assimilating and high-ethanol-producing yeasts by protoplast fusion. Appl. Environ. Microbiol. 51(2), 362-367.
  66. Faria, J.T.D., Rocha, P.F., Converti, A., Passos, F.M., Minim, L.A., Sampaio, F.C., 2013. Statistical investigation of Kluyveromyces lactis cells permeabilization with ethanol by response surface methodology. Braz. J. Microbiol. 44, 1067-1074.
  67. Farkas, C., Rezessy-Szabo, J.M., Gupta, V.K., Bujna, E., Pham, T.M., Pásztor-Huszár, K., Friedrich, L., Bhat, R., Thakur, V.K., Nguyen, Q.D., 2019. Batch and fed-batch ethanol fermentation of cheese-whey powder with mixed cultures of different yeasts. 12(23), 4495.
  68. Fassina, P., Nunes, G.Q., Adami, F.S., Goettert, M.I., Volken de Souza, C.F., 2019. Importance of cheese whey processing: supplements for sports activities-a review. J. Food Nutr. Sci. 69(1), 83-99.
  69. Fernández-Gutiérrez, D., Veillette, M., Giroir-Fendler, A., Ramirez, A.A., Faucheux, N., Heitz, M., 2017. Biovalorization of saccharides derived from industrial wastes such as whey: a review. Rev. Environ. Sci. Biotechnol. 16(1), 147-174.
  70. Ferreira, P.G., da Silveira, F.A., dos Santos, R.C.V., Genier, H.L.A., Diniz, R.H.S., Ribeiro, J.I., Fietto, L.G., Passos, F.M.L., da Silveira, W.B., 2015. Optimizing ethanol production by thermotolerant Kluyveromyces marxianus CCT 7735 in a mixture of sugarcane bagasse and ricotta whey. Food Sci. Biotechnol. 24(4), 1421-1427.
  71. Fonseca, G.G., Heinzle, E., Wittmann, C., Gombert, A.K., 2008. The yeast Kluyveromyces marxianus and its biotechnological potential. Appl. Microbiol. Biotechnol. 79(3), 339-354.
  72. Gabardo, S., Rech, R., Ayub, M.A.Z., 2012. Performance of different immobilized-cell systems to efficiently produce ethanol from whey: fluidized batch, packed-bed and fluidized continuous bioreactors. J. Chem. Technol. Biotechnol. 87(8), 1194-1201.
  73. Gänzle, M.G., Haase, G., Jelen, P., 2008. Lactose: crystallization, hydrolysis and value-added derivatives. Int. Dairy J. 18(7), 685-694.
  74. Goffrini, P., Ferrero, I., Donnini, C., 2002. Respiration-dependent utilization of sugars in yeasts: a determinant role for sugar transporters. J. Bacteriol. 184(2), 427-432.
  75. Gomes, D.G., Teixeira, J.A., Domingues, L., 2021a. Economic determinants on the implementation of a Eucalyptus wood biorefinery producing biofuels, energy and high added-value compounds. Appl. Energy. 303, 117662.
  76. Gomes, D., Cruz, M., de Resende, M., Ribeiro, E., Teixeira, J., Domingues, L., 2021b. Very high gravity bioethanol revisited: main challenges and advances. Fermentation. 7(1), 38.
  77. Gomez-Ruiz, L., Garcia-Garibay, M., Barzana, E., 1988. Utilization of endo-polygalacturonase from Kluyveromyces fragilis in the clarification of apple juice. J. Food Sci. 53(4), 1236-1238.
  78. González-Siso, M.I., 1996. The biotechnological utilization of cheese whey: a review. Bioresour. Technol. 57(1), 1-11.
  79. González-Siso, M.I., García-Leiro, A., Tarrío, N., Cerdán, M.E., 2009. Sugar metabolism, redox balance and oxidative stress response in the respiratory yeast Kluyveromyces lactis. Cell Fact. 8(1), 46.
  80. González-Siso, M.I., Touriño, A., Vizoso, Á., Pereira-Rodríguez, Á., Rodríguez-Belmonte, E., Becerra, M., Cerdán, M.E., 2015. Improved bioethanol production in an engineered Kluyveromyces lactis strain shifted from respiratory to fermentative metabolism by deletion of NDI1. Microb. Biotechnol. 8(2), 319-330.
  81. Gosling, A., Stevens, G.W., Barber, A.R., Kentish, S.E., Gras, S.L., 2010. Recent advances refining galactooligosaccharide production from lactose. Food Chem. 121(2), 307-318.
  82. Guimarães, P.M., Teixeira, J.A., Domingues, L., 2010. Fermentation of lactose to bio-ethanol by yeasts as part of integrated solutions for the valorisation of cheese whey. Adv. 28(3), 375-384.
  83. Guimarães, Pedro M. R., Le Berre, V., Sokol, S., François, J., Teixeira, J.A., Domingues, L., 2008a. Comparative transcriptome analysis between original and evolved recombinant lactose-consuming Saccharomyces cerevisiae Biotechnol. J.: Healthcare Nutr. Technol. 3(12), 1591-1597.
  84. Guimarães, P.M., Teixeira, J.A., Domingues, L., 2008b. Fermentation of high concentrations of lactose to ethanol by engineered flocculent Saccharomyces cerevisiae. Biotechnol. Lett. 30(11), 1953-1958.
  85. Guimarães, Pedro M R, François, J., Luc, J., Teixeira, J.A., Domingues, L., 2008c. Adaptive evolution of a lactose-consuming Saccharomyces cerevisiae Appl. Environ. Microbiol. 74(6), 1748-1756.
  86. Gunasekaran, S., Ko, S., Xiao, L., 2007. Use of whey proteins for encapsulation and controlled delivery applications. J. Food Eng. 83(1), 31-40.
  87. Guo, X., Zhou, J., Xiao, D., 2010. Improved ethanol production by mixed immobilized cells of Kluyveromyces marxianus and Saccharomyces cerevisiae from cheese whey powder solution fermentation. Appl. Biochem. Biotechnol. 160(2), 532-538.
  88. Guo, X., Wang, R., Chen, Y., Xiao, D., 2012. Intergeneric yeast fusants with efficient ethanol production from cheese whey powder solution: construction of a Kluyveromyces marxianus and Saccharomyces cerevisiae AY-5 hybrid. Eng. Life Sci. 12(6), 656-661.
  89. Hou, L., Jia, L., Morrison, H.M., Majumder, E.L.W., Kumar, D., 2021. Enhanced polyhydroxybutyrate production from acid whey through determination of process and metabolic limiting factors. Bioresour. Technol. 342, 125973.
  90. Janssens, J.H., Burris, N., Woodward, A., Bailey, R.B., 1983. Lipid-enhanced ethanol production by Kluyveromyces fragilis. Appl. Environ. Microbiol. 45(2), 598-602.
  91. Jenq, W., Speckman, R.A., Crang, R.E., Steinberg, M.P., 1989. Enhanced conversion of lactose to glycerol by Kluyveromyces fragilis utilizing whey permeate as a substrate. Appl. Environ. Microbiol. 55(3), 573-578.
  92. Jeong, Y.S., Vieth, W.R., Matsuura, T., 1991. Fermentation of lactose to ethanol with recombinant yeast in an immobilized yeast membrane bioreactor. Biotechnol. Bioeng. 37(6), 587-590.
  93. Jiang, L., Cui, H., Zhu, L., Hu, Y., Xu, X., Li, S., Huang, H., 2015. Enhanced propionic acid production from whey lactose with immobilized Propionibacterium acidipropionici and the role of trehalose synthesis in acid tolerance. Green Chem. 17(1), 250-259.
  94. Juraščík, M., Guimarães, P., Klein, J., Domingues, L., Teixeira, J., Markoš, J., 2006. Kinetics of lactose fermentation using a recombinant Saccharomyces cerevisiae Biotechnol. Bioeng. 94(6), 1147-1154.
  95. Kasmi, M., 2018. Biological processes as promoting way for both treatment and valorization of dairy industry effluents. Waste Biomass Valorization. 9(2), 195-209.
  96. Kaur, R., Panesar, P.S., Singh, R.S., 2015. Utilization of whey for the production of β-galactosidase using yeast and fungal culture. World Acad. Sci. Eng. Technol. 9(7), 690-694.
  97. Kelbert, M., Romaní, A., Coelho, E., Pereira, F.B., Teixeira, J.A., Domingues, L., 2015. Lignocellulosic bioethanol production with revalorization of low-cost agroindustrial by-products as nutritional supplements. Crop. Prod. 64, 16-24.
  98. Knob, A., Izidoro, S.C., Lacerda, L.T., Rodrigues, A., de Lima, V.A., 2020. A novel lipolytic yeast Meyerozyma guilliermondii: efficient and low-cost production of acid and promising feed lipase using cheese whey. Biocatal. Agric. Biotechnol. 24, 101565.
  99. Kokkiligadda, A., Beniwal, A., Saini, P., Vij, S., 2016. Utilization of cheese whey using synergistic immobilization of β-galactosidase and Saccharomyces cerevisiae cells in dual matrices. Appl. Biochem. Biotechnol. 179(8), 1469-1484.
  100. Korhonen, H., 2009. Milk-derived bioactive peptides: from science to applications. J. Funct. Foods. 1(2), 177-187.
  101. Koushki, M., Jafari, M., Azizi, M., 2012. Comparison of ethanol production from cheese whey permeate by two yeast strains. J. Food Sci. Technol. 49(5), 614-619.
  102. Kumari, S., Panesar, P.S., Kaur, R., Bera, M.B., 2019. Statistical modeling of β-galactosidase production from novel yeast isolate using cheese whey. J. Sci. Ind. Res. 78(2), 81-85.
  103. Lappa, I.K., Kachrimanidou, V., Papadaki, A., Stamatiou, A., Ladakis, D., Eriotou, E., Kopsahelis, N., 2021. A comprehensive bioprocessing approach to foster cheese whey valorization: on-site β-galactosidase secretion for lactose hydrolysis and sequential bacterial cellulose production. Fermentation. 7(3), 184.
  104. Lappa, I.K., Papadaki, A., Kachrimanidou, V., Terpou, A., Koulougliotis, D., Eriotou, E., Kopsahelis, N., 2019. Cheese whey processing: integrated biorefinery concepts and emerging food applications. Foods. 8(8), 347.
  105. Lawton, M.R., Alcaine, S.D., 2019. Leveraging endogenous barley enzymes to turn lactose-containing dairy by-products into fermentable adjuncts for Saccharomyces cerevisiae-based ethanol fermentations. J. Dairy Sci. 102(3), 2044-2050.
  106. Lee, S.E., Lee, C.G., Kang, D.H., Lee, H.Y., Jung, K.H., 2012.Preparation of corncob grits as a carrier for immobilizing yeast cells for ethanol production. J. Microbiol. Biotechnol. 22(12), 1673-1680.
  107. Liu, J.J., Zhang, G.C., Oh, E.J., Pathanibul, P., Turner, T.L., Jin, Y.S., 2016. Lactose fermentation by engineered Saccharomyces cerevisiae capable of fermenting cellobiose. J. Biotechnol. 234, 99-104.
  108. Liu, J.J., Zhang, G.C., Kwak, S., Oh, E.J., Yun, E.J., Chomvong, K., Cate, J.H., Jin, Y.S., 2019. Overcoming the thermodynamic equilibrium of an isomerization reaction through oxidoreductive reactions for biotransformation. Nat. Commun. 10(1), 1-8.
  109. Magalhães, K., Pereira, M., Nicolau, A., Dragone, G., 2010. Production of fermented cheese whey-based beverage using kefir grains as starter culture: evaluation of morphological and microbial variations. Bioresour. Technol. 101(22), 8843-8850.
  110. Magalhães, K.T., Dias, D.R., de Melo Pereira, G.V., Oliveira, J.M., Domingues, L., Teixeira, J.A., de Almeida e Silva, J.B., Schwan, R.F., 2011a. Chemical composition and sensory analysis of cheese whey-based beverages using kefir grains as starter culture. Int. J. Food Sci. Technol. 46(4), 871-878.
  111. Magalhães, K.T., Dragone, G., De Melo Pereira, G.V., Oliveira, J.M., Domingues, L., Teixeira, J.A., e Silva, J.B.A., Schwan, R.F., 2011b. Comparative study of the biochemical changes and volatile compound formations during the production of novel whey-based kefir beverages and traditional milk kefir. Food Chem. 126(1), 249-253.
  112. Magalhães-Guedes, K., Rodrigues, A.K., Gervasio, I.M., Gervasio, I., Peraro Do Nascimento, A., Schwan, R.F., 2013. Ethanol production from deproteinized cheese whey fermentations by co-cultures of Kluyveromyces marxianus and Saccharomyces cerevisiae. Afr. J. Microbiol. Res. 7(13), 1121-1127.
  113. Mangiagalli, M., Lotti, M., 2021. Cold-active β-galactosidases: insight into cold adaptation mechanisms and biotechnological exploitation. Mar. Drugs. 19(1), 43.
  114. Mansour, M.H., Ghaly, A.E., Ben-Hassan, R.M., Nassar, M.A., 1993. Modeling batch production of single cell protein from cheese whey. Appl. Biochem. Biotechnol. 43(1), 1-14.
  115. Modler, W., 2009. Value-added components derived from whey. Am. Dairy Sci. Assoc. 1.
  116. Mollea, C., Marmo, L., Bosco, F., 2013. Valorisation of cheese whey, a by-product from the dairy industry, in: Food Industry.
  117. Mudgil, D., Barak, S., 2019. Dairy-based functional beverages, in: Milk-Based Beverages. Woodhead Publishing, 67-93.
  118. Murari, C.S., Machado, W.R.C., Schuina, G.L., Del Bianchi, V.L., 2019. Optimization of bioethanol production from cheese whey using Kluyveromyces marxianus URM 7404. Biocatal. Agric. Biotechnol. 20, 101182.
  119. Myers R.H., Montgomery, D.C., Anderson-Cook., C.M., 2016. Response surface methodology: process and product optimization using designed experiments, 4th John Wiley & Sons.
  120. Nagarajan, D., Nandini, A., Dong, C.D., Lee, D.J., Chang, J.S., 2020. Lactic acid production from renewable feedstocks using poly(vinyl alcohol)-Immobilized lactobacillus plantarum Ind. Eng. Chem. Res. 59(39), 17156-17164.
  121. Nasrabadi, M.R.N., Razavi, S.H., 2011. Optimization of β-carotene production by a mutant of the lactosepositive yeast Rhodotorula acheniorum from whey ultrafiltrate. Food Sci. Biotechnol. 20(2), 445-454.
  122. Nayak, J., Pal, P., 2013. Transforming waste cheese-whey into acetic acid through a continuous membrane-integrated hybrid process. Ind. Eng. Chem. Res. 52(8), 2977-2984.
  123. Nehlin, J.O., Carlberg, M., Ronne, H., 1989. Yeast galactose permease is related to yeast and mammalian glucose transporters. 85(2), 313-319.
  124. Nicolás, P., Ferreira, M.L., Lassalle, V., 2019. A review of magnetic separation of whey proteins and potential application to whey proteins recovery, isolation and utilization. J. Food Eng. 246, 7-15.
  125. Obruca, S., Marova, I., Melusova, S., Mravcova, L., 2011. Production of polyhydroxyalkanoates from cheese whey employing Bacillus megaterium CCM 2037. Ann. Microbiol. 61(4), 947-953.
  126. Oda, Y., Nakamura, K., 2009. Production of ethanol from the mixture of beet molasses and cheese whey by a 2-deoxyglucose-resistant mutant of Kluyveromyces marxianus. FEMS Yeast Res. 9(5), 742-748.
  127. Oliveira, C., Teixeira, J.A., Lima, N., Da Silva, N.A., Domingues, L., 2007. Development of stable flocculent Saccharomyces cerevisiae strain for continuous Aspergillus niger β-galactosidase production. J. Biosci. Bioeng. 103(4), 318-324.
  128. Oliveira, C., Guimarães, P.M.R., Domingues, L., 2011. Recombinant microbial systems for improved β-galactosidase production and biotechnological applications. Biotechnol. Adv. 29(6), 600-609.
  129. Omwene, P.I., Yağcıoğlu, M., Öcal-Sarihan, Z.B., Ertan, F., Keris-Sen, Ü.D., Karagunduz, A., Keskinler, B., 2021. Batch fermentation of succinic acid from cheese whey by Actinobacillus succinogenes under variant medium composition. 3 Biotech. 11(8), 1-10.
  130. Otto, R.T., Daniel, H.J., Pekin, G., Müller-Decker, K., Fürstenberger, G., Reuss, M., Syldatk, C., 1999. Production of sophorolipids from whey: II. product composition, surface active properties, cytotoxicity and stability against hydrolases by enzymatic treatment. Microbiol. Biotechnol. 52(4), 495-501.
  131. Pais, J., Serafim, L.S., Freitas, F., Reis, M.A., 2016. Conversion of cheese whey into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by Haloferax mediterranei. New Biotechnol. 33(1), 224-230.
  132. Pandey, A., Srivastava, S., Rai, P., Duke, M., 2019. Cheese whey to biohydrogen and useful organic acids: a non-pathogenic microbial treatment by acidophilus. Sci. Rep. 9(1), 1-9.
  133. Panesar, P.S., Kennedy, J.F., Gandhi, D.N., Bunko, K., 2007. Bioutilisation of whey for lactic acid production. Food Chem. 105(1), 1-14.
  134. Parashar, A., Jin, Y., Mason, B., Chae, M., Bressler, D.C., 2016. Incorporation of whey permeate, a dairy effluent, in ethanol fermentation to provide a zero waste solution for the dairy industry. J. Dairy Sci. 99(3), 1859-1867.
  135. Paterson, A.H.J., 2009. Production and uses of lactose, in: Adv. Dairy Chem. pp. 105-120.
  136. Pereira, F.B., Guimarães, P.M., Teixeira, J.A., Domingues, L., 2011a. Robust industrial Saccharomyces cerevisiae strains for very high gravity bio-ethanol fermentations. J. Biosci. Bioeng. 112(2), 130-136.
  137. Pereira, F.B, Guimarães, P.M., Gomes, D.G., Mira, N.P., Teixeira, M.C., Sá-Correia, I., Domingues, L., 2011b. Identification of candidate genes for yeast engineering to improve bioethanol production in very high gravity and lignocellulosic biomass industrial fermentations. Biotechnol. Biofuels. 4(1), 57.
  138. Pescuma, M., de Valdez, G.F., Mozzi, F., 2015. Whey-derived valuable products obtained by microbial fermentation. Appl. Microbiol. Biotechnol. 99(15), 6183-6196.
  139. Petrova, V.Y., Kujumdzieva, A.V., 2010. Thermotolerant yeast strains producers of galacto-oligosaccharides. Biotechnol. Biotechnol. Equip. 24(1), 1612-1619.
  140. Perini, B.L.B., Souza, H.C.M., Kelbert, M., Apati, G.P., Pezzin, A.P.T., Schneider, A.L.S., Production of β-galactosidase from cheese whey using Kluyveromyces marxianus CBS 6556, Chem. Eng. Trans. 32, 991-996.
  141. Pignatelli, R., Vai, M., Alberghina, L., Popolo, L., 1998. Expression and secretion of Beta-galactosidase in Saccharomyces cerevisiae using the signal sequences of ggpi, the major yeast glycosylphosphatidylinositol-containing protein. Biotechnol. Appl. Biochem. 27(2), 81-88.
  142. Pinheiro, T., Lip, K.Y.F., García-Ríos, E., Querol, A., Teixeira, J., van Gulik, W., Guillamón, J.M., Domingues, L., 2020. Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions. Sci. Rep. 10(1), 1-17.
  143. Pires, A.F., Marnotes, N.G., Rubio, O.D., Garcia, A.C., Pereira, C.D., 2021. Dairy by-products: a review on the valorization of whey and second cheese whey. Foods. 10(5), 1067.
  144. Plessas, S., Bosnea, L., Psarianos, C., Koutinas, A.A., Marchant, R., Banat, I.M., 2008. Lactic acid production by mixed cultures of Kluyveromyces marxianus, Lactobacillus delbrueckii ssp. bulgaricus and Lactobacillus helveticus. Bioresour. Technol. 99(13), 5951-5955.
  145. Poch, O., L’Hôte, H., Dallery, V., Debeaux, F., , Fleer, R., Sodoyer, R., 1992Sequence of the Kluyveromyces lactis β-galactosidase: comparison with prokaryotic enzymes and secondary structure analysis. Gene. 118(1), 55-63.
  146. Porro, D., Martegani, E., Ranzi, B.M., Alberghina, L., 1992. Lactose/whey utilization and ethanol production by transformed Saccharomyces cerevisiae Biotechnol. Bioeng. 39(8), 799-805.
  147. Pouliot, Y., 2008. Membrane processes in dairy technology-From a simple idea to worldwide panacea. Dairy J. 18(7), 735-740.
  148. Prazeres, A.R., Carvalho, F., Rivas, J., 2012. Cheese whey management: a review. J. Environ. Manage. 110, 48-68.
  149. Rama, G.R., Kuhn, D., Beux, S., Maciel, M.J., Volken de Souza, C.F.V., 2019. Potential applications of dairy whey for the production of lactic acid bacteria cultures. Int. Dairy J. 98, 25-37.
  150. Rao, R., Basak, N., 2021. Fermentative molecular biohydrogen production from cheese whey: present prospects and future strategy. Appl. Biochem. Biotechnol. 193, 2297-2330.
  151. Rapin, J.D., Marison, I.W., von Stockar, U., Reilly, P.J., 1994. Glycerol production by yeast fermentation of whey permeate. Enzyme Microb. Technol. 16(2), 143-150.
  152. Rocha, J.M., Guerra, A., 2020. On the valorization of lactose and its derivatives from cheese whey as a dairy industry by-product: an overview. Eur. Food Res. Technol. 246, 2161-2174.
  153. Rodríguez, Á.P., Leiro, R.F., Cristina, M.C., Cerdán, M.E., Siso, M.I.G., Becerra, M., 2006. Secretion and properties of a hybrid Kluyveromyces lactis-Aspergillus niger β-galactosidase. Microb. Cell Fact. 5(1), 41.
  154. Jelen, P., 2003. Whey processing, utilization and products. Encycl. Dairy Sci. Academic Press, London. pp. 2739-2745.
  155. Rollini, M., Musatti, A., Cavicchioli, D., Bussini, D., Farris, S., Rovera, C., Romano, D., De Benedetti, S., Barbiroli, A., 2020. From cheese whey permeate to Sakacin-A/bacterial cellulose nanocrystal conjugates for antimicrobial food packaging applications: a circular economy case study. Sci. Rep. 10(1), 1-14.
  156. Roohina, F., Mohammadi, M., Najafpour, G.D., 2016. Immobilized Kluyveromyces marxianus cells in carboxymethyl cellulose for production of ethanol from cheese whey: experimental and kinetic studies. Bioprocess. Biosyst. Eng. 39(9), 1341-1349.
  157. Rosa, J.C.C., Colombo, L.T., Alvim, M.C.T., Avonce, N., Van Dijck, P., Passos, F.M.L., 2013. Metabolic engineering of Kluyveromyces lactis for L-ascorbic acid (vitamin C) biosynthesis. Microb. Cell Fact. 12(1), 59.
  158. Rubio-Texeira, M., Castrillo, J.I., Adam, A.C., Ugalde, U.O., Polaina, J., 1998. Highly efficient assimilation of lactose by a metabolically engineered strain of Saccharomyces cerevisiae. Yeast. 14(9), 827-837.
  159. Ryan, M.P., Walsh, G., 2016. The biotechnological potential of whey. Rev. Environ. Sci. Biotechnol. 15(3), 479-498.
  160. Ryu, Y.W., Jang, H.W., Lee, H.S., 1991. Enhancement of ethanol tolerance of lactose assimilating yeast strain by protoplast fusion. J. Microbiol. Biotechnol. 1(3), 151-156.
  161. Saini, P., Beniwal, A., Kokkiligadda, A., Vij, S., 2017a. Evolutionary adaptation of Kluyveromyces marxianus strain for efficient conversion of whey lactose to bioethanol. Process Biochem. 62, 69-79.
  162. Saini, P., Beniwal, A., Vij, S., 2017b. Comparative analysis of oxidative stress during aging of Kluyveromyces marxianus in synthetic and whey media. Appl. Biochem. Biotechnol. 183(1), 348-361.
  163. Sampaio, F.C., Faria, J.T., Silva, M.F., de Souza Oliveira, R.P., Converti, A., 2019. Cheese whey permeate fermentation by Kluyveromyces lactis: a combined approach to wastewater treatment and bioethanol production. Environ. Technol. 41(24), 3210-3218.
  164. Sansonetti, S., Curcio, S., Calabrò, V., Iorio, G., 2009. Bio-ethanol production by fermentation of ricotta cheese whey as an effective alternative non-vegetable source. Biomass Bioenergy. 33(12), 1687-1692.
  165. Sanz, P., Randez‐Gil, F., Prieto, J.A., 1994. Molecular characterization of a gene that confers 2‐deoxyglucose resistance in yeast. Yeast. 10(9), 1195-1202.
  166. Saqib, S., Akram, A., Halim, S.A., Tassaduq, R., 2017. Sources of β-galactosidase and its applications in food industry. 3 Biotech. 7(1), 79.
  167. Schultz, N., Chang, L., Hauck, A., Reuss, M., Syldatk, C., 2006. Microbial production of single-cell protein from deproteinized whey concentrates. Appl. Microbiol. Biotechnol. 69(5), 515-520.
  168. Seo, Y.H., Lee, I., Jeon, S.H., Han, J.I., 2014. Efficient conversion from cheese whey to lipid using Cryptococcus curvatus. Eng. J. 90, 149-153.
  169. Silva, A.C., Guimarães, P.M., Teixeira, J.A., Domingues, L., 2010. Fermentation of deproteinized cheese whey powder solutions to ethanol by engineered Saccharomyces cerevisiae: effect of supplementation with corn steep liquor and repeated-batch operation with biomass recycling by flocculation. J. Ind. Microbiol. Biotechnol. 37(9), 973-982.
  170. Silveira, W.B., Passos, F.J.V., Mantovani, H.C., 2005. Ethanol production from cheese whey permeate by Kluyveromyces marxianus UFV-3: a flux analysis of oxido-reductive metabolism as a function of lactose. Enzyme Microb. Technol. 36(7), 930-936.
  171. Silveira, F.A., Oliveira Soares, D.L., Bang, K.W., Balbino, T.R., de Moura Ferreira, M.A., Diniz, R.H.S., de Lima, L.A., Brandão, M.M., Villas-Bôas, S.G., da Silveira, W.B., 2020. Assessment of ethanol tolerance of Kluyveromyces marxianus CCT 7735 selected by adaptive laboratory evolution. Appl. Microbiol. Biotechnol. 104(17), 7483-7494.
  172. Smithers, G.W., 2008. Whey and whey proteins-From “gutter-to-gold”. Int. Dairy J. 18(7), 695-704.
  173. Smithers, G.W., 2015. Whey-ing up the options-yesterday, today and tomorrow. Int. Dairy J. 48, 2-14.
  174. Snoek, I.I., Steensma, H., 2006. Why does Kluyveromyces lactis not grow under anaerobic conditions? comparison of essential anaerobic genes of Saccharomyces cerevisiae with the Kluyveromyces lactis FEMS yeast Res. 6(3), 393-403.
  175. Soupioni, M., Golfinopoulos, A., Kanellaki, M., Koutinas, A.A., 2013. Study of whey fermentation by kefir immobilized on low cost supports using 14C-labelled lactose. Bioresour. Technol. 145, 326-330.
  176. Sreekrishna, K., Dickson, R.C., 1985. Construction of strains of Saccharomyces cerevisiae that grow on lactose. Proc. Natl. Acad. Sci. U.S.A. 82(23), 7909-7913.
  177. Sun, H., You, S., Wang, M., Qi, W., Su, R., He, Z., 2016. Recyclable strategy for the production of high-purity galacto-oligosaccharides by Kluyveromyces lactis. J. Agric. Food Chem. 64(28), 5679-5685.
  178. Taskin, M., Saghafian, A., Aydogan, M.N., Arslan, N.P., 2015. Microbial lipid production by cold-adapted oleaginous yeast Yarrowia lipolytica B9 in non-sterile whey medium. Biofuels, Bioprod. Biorefin. 9(5), 595-605.
  179. Taya, M., Honda, H., Kobayashi, T., 1984. Lactose-utilizing hybrid strain derived from Saccharomyces cerevisiae and Kluyveromyces lactis by protoplast fusion. Agric. Biol. Chem. 48(9), 2239-2243.
  180. Terrell, S.L., Bernard, A., Bailey, R.B., 1984. Ethanol from whey: continuous fermentation with a catabolite repression-resistant Saccharomyces cerevisiae Appl. Environ. Microbiol. 48(3), 577-580.
  181. Tomaszewska, M., Białończyk, L., 2016. Ethanol production from whey in a bioreactor coupled with direct contact membrane distillation, in: Catal. Today. Elsevier. 268 pp. 156-163.
  182. Turner, T.L., Kim, E., Hwang, C., Zhang, G., Liu, J., Jin, Y., 2017. Short communication: conversion of lactose and whey into lactic acid by engineered yeast. J. Dairy Sci. 100(1), 124-128.
  183. Uncu, O.N., Cekmecelioglu, D., 2011. Cost-effective approach to ethanol production and optimization by response surface methodology. Waste Manage. 31(4), 636-643.
  184. Castillo, V.M., Pachapur, L., Kaur Brar, S., Naghdi, M., Arriaga, S., Ávalos Ramirez, A., 2020.Yeast-driven whey biorefining to produce value-added aroma, flavor, and antioxidant compounds: technologies, challenges, and alternatives. Crit. Rev. Biotechnol. 40(7), 930-950.
  185. van Dijk, M., Mierke, F., Nygård, Y., Olsson, L., 2020. Nutrient-supplemented propagation of Saccharomyces cerevisiae improves its lignocellulose fermentation ability. AMB Express. 10(1), 1-10.
  186. van Ooyen, A.J., Dekker, P., Huang, M., Olsthoorn, M.M., Jacobs, D.I., Colussi, P.A., Taron, C.H., 2006. Heterologous protein production in the yeast Kluyveromyces lactis. FEMS Yeast Res. 6(3), 381-392.
  187. Venturini, M., Morrione, A., Pisarra, P., Martegani, E., Vanoni, M., 1997. In Saccharomyces cerevisiae a short amino acid sequence facilitates excretion in the growth medium of periplasmic proteins. Mol. Microbiol. 23(5), 997-1007.
  188. Vyas, S., Chhabra, M., 2019. Assessing oil accumulation in the oleaginous yeast Cystobasidium oligophagum JRC1 using dairy waste cheese whey as a substrate. 3 Biotech. 9(5), 173.
  189. Wanarska, M., Kur, J., 2012. A method for the production of D-tagatose using a recombinant Pichia pastoris strain secreting β-D-galactosidase from Arthrobacter chlorophenolicus and a recombinant L-arabinose isomerase from Arthrobacter sp. 22c. Microb. Cell Fact. 11(1), 113.
  190. Watanabe, T., Shinozaki, Y., Suzuki, K., Koitabashi, M., Yoshida, S., Sameshima-Yamashita, Y., Kuze Kitamoto, H.K., 2014. Production of a biodegradable plastic-degrading enzyme from cheese whey by the phyllosphere yeast Pseudozyma antarctica GB-4(1)W. J. Biosci. 118(2), 183-187.
  191. Wen-qiong, W., Yun-chao, W., Xiao-feng, Z., Rui-xia, G., Mao-lin, L., 2019. Whey protein membrane processing methods and membrane fouling mechanism analysis. Food Chem. 289, 468-481.
  192. Wolf, K., Zimmermann, M., Sipiczki, M., 1996. Protoplast fusion of yeasts, in: Nonconventional yeasts in biotechnology. Springer Berlin Heidelberg, pp. 83-99.
  193. Yadav, J.S.S., Bezawada, J., Ajila, C.M., Yan, S., Tyagi, R.D., Surampalli, R.Y., 2014. Mixed culture of Kluyveromyces marxianus and Candida krusei for single-cell protein production and organic load removal from whey. Bioresour. Technol. 164, 119-127.
  194. Yadav, J.S.S., Yan, S., Pilli, S., Kumar, L., Tyagi, R.D., Surampalli, R.Y., 2015. Cheese whey: a potential resource to transform into bioprotein, functional/nutritional proteins and bioactive peptides. Biotechnol. Adv. 33(6), 756-774.
  195. You, K.M., Rosenfield, C.L., Knipple, D.C., 2003. Ethanol tolerance in the yeast Saccharomyces cerevisiae is dependent on cellular oleic acid content. Appl. Environ. Microbiol. 69(3), 1499-1503.
  196. You, S., Zhang, J., Yin, Q., Qi, W., Su, R., He, Z., 2017. Development of a novel integrated process for co-production of Β-galactosidase and ethanol using lactose as substrate. Bioresour. Technol. 230, 15-23.
  197. Zafar, S., Owais, M., 2006. Ethanol production from crude whey by Kluyveromyces marxianus. Biochem. Eng. J. 27(3), 295-298.
  198. Zara, G., Angelozzi, D., Belviso, S., Bardi, L., Goffrini, P., Lodi, T., Budroni, M., Mannazzu, I., 2009. Oxygen is required to restore flor strain viability and lipid biosynthesis under fermentative conditions. FEMS Yeast Res. 9(2), 217-225.
  199. Zhou, X., Hua, X., Huang, L., Xu, Y., 2019. Bio-utilization of cheese manufacturing wastes (cheese whey powder) for bioethanol and specific product (galactonic acid) production via a two-step bioprocess. Bioresour. Technol. 272, 70-76.
  200. Zikmanis, P., Kolesovs, S., Semjonovs, P., 2020. Production of biodegradable microbial polymers from whey. Bioresour. Bioprocess. 7(1), 36.
  201. Zohri, A.N.A., Ragab, S.W., Mekawi, M.I., Mostafa, O.A.A., 2017. Comparison between batch, fed-batch, semi-continuous and continuous techniques for bio-ethanol production from a mixture of egyptian cane and beet molasses. Sugar J. 9, 89-111.
  202. Zoppellari, F., Bardi, L., 2013. Production of bioethanol from effluents of the dairy industry by Kluyveromyces marxianus. N. Biotechnol. 30(6), 607-613.
  203. Zotta, T., Solieri, L., Iacumin, L., Picozzi, C., Gullo, M., 2020. Valorization of cheese whey using microbial fermentations. Appl. Microbiol. Biotechnol. 104(7), 2749-2764.
  204. Zou, J., Guo, X., Shen, T., Dong, J., Zhang, C., Xiao, D., 2013. Construction of lactose-consuming Saccharomyces cerevisiae for lactose fermentation into ethanol fuel. J. Ind. Microbiol. Biotechnol. 40(3-4), 353-363.
  205. Zou, J., Chen, X., Hu, Y., Xiao, D., Guo, X., Chang, X.,  Zhou, L., 2021. Uncoupling glucose sensing from GAL metabolism for heterologous lactose fermentation in Saccharomyces cerevisiae. Biotechnol. Lett., 43(8), 1607-1616.