Ферментативный способ производства биоактивных пептидов из молочного белкового сырья: обзор предметного поля

Введение: На протяжении 14 лет интерес к использованию молочного сырья для производства биологически активных пептидов (БАП) с антигипертензивным, антиоксидантным и антидиабетическим действием находился в фазе стремительного роста по причине необходимости профилактики различных заболеваний. На сегодняшний день особое внимание уделяется ферментативному способу производства, так как он позволяет направленно осуществлять процесс высвобождения БАП с заданными свойствами.

Целью данного обзора предметного поля являлось обобщение и систематизация опыта международных исследований за последние 14 лет в области ферментативного гидролиза как способа высвобождения БАП из молочного сырья.

Материалы и методы: Данный обзор предметного поля был выполнен в соответствии с руководством PRISMA-ScR. Поиск научных трудов был осуществлен в базе данных Google Scholar, так как она позволяет осуществлять поиск научных источников без ограничений по их формату и виду представления научных данных (книга, диссертация, статья), а также включает в себя научные источники из других баз данных и производит сортировку по релевантности.

Результаты:  При поиске было выявлено 72 источника, опубликованных с 2007 по 2021 гг. на английском языке. Отобранные работы посвящены вопросам гидролиза микробными протеазами (МП) – 50%, и коммерческими ферментными препаратами (КФП) – 50%.

Выводы: Существует ряд задач, решение которых необходимо для повышения уровня коммерциализации научных данных о процессе производства БАП посредством направленного гидролиза. Создание новых баз данных; наращивание исследовательской базы по совместной ферментации микроорганизмами и коммерческими ферментами; определение генов протеаз методом ПЦР позволят повысить практическую применимость исследований и обоснованность проведения бóльшего количества доказательных in vivo и клинических исследований.

1. Abd El-Salam, M. H., El-Shibiny, S. (2015). Preparation, properties, and uses of enzymatic milk protein hydrolysates. Critical Reviews in Food Science and Nutrition, 57(6), 1119–1132. https://doi.org/10.1080/10408398.2014.899200

2. Adjonu, R., Doran, G., Torley, P., Agboola, S. (2013). Screening of whey protein isolate hydrolysates for their dual functionality: Influence of heat pre-treatment and enzyme specificity. Food Chemistry, 136(3–4), 1435–1443. https://doi.org/10.1016/j.foodchem.2012.09.053

3. Agarkova, E., Kruchinin, A., Zolotaryov, N., Pryanichnikova, N., Belyakova, Z., Fedorova, T. (2020). Processing cottage cheese whey components for functional food production. Foods and Raw Materials, 8(1), 52–59. https://doi.org/10.21603/2308-4057-2020-1-52-59

4. Agyei, D., He, L. (2015). Evaluation of cross-linked enzyme aggregates of Lactobacillus cell-envelope proteinases, for protein degradation. Food and Bioproducts Processing, 94, 59–69. https://doi.org/10.1016/j.fBP.2015.01.004

5. Agyei, D., Lim, W., Zass, M., Tan, D., Danquah, M. K. (2013). Bioanalytical evaluation of Lactobacillus delbrueckii subsp. lactis 313 cell-envelope proteinase extraction. Chemical Engineering Science, 95, 323–330. https://doi.org/10.1016/j.ces.2013.03.049

6. Ahn, J.E., Park, S.Y., Lee, B.H. (2007) Optimization of Whey-Based Medium for Growth and ACE-Inhibitory Activity of Lactobacillus brevis. Korean Journal of Dairy Science and Biotechnology, 25(1), 1-7.

7. Ahtesh, F. B., Stojanovska, L., Apostolopoulos, V. (2017). Processing and sensory characteristics of a fermented low-fat skim milk drink containing bioactive antihypertensive peptides, a functional milk product. International Journal of Dairy Technology, 71, 230–239. https://doi.org/10.1111/1471-0307.12479

8. Augustin, M. A., Udabage, P. (2007). Influence of processing on functionality of milk and dairy proteins. In Advances in Food and Nutrition Research (pp. 1–38). Elsevier. http://dx.doi.org/10.1016/s1043-4526(07)53001-9

9. Bamdad, F., Bark, S., Kwon, C. H., Suh, J.-W., Sunwoo, H. (2017). Anti-Inflammatory and Antioxidant Properties of Peptides Released from β-Lactoglobulin by High Hydrostatic Pressure-Assisted Enzymatic Hydrolysis. Molecules, 22(6), 949. https://doi.org/10.3390/molecules22060949

10. Cheison, S. C., Bor, E. K., Faraj, A. K., Kulozik, U. (2012). Selective hydrolysis of α-lactalbumin by Acid Protease A offers potential for β-lactoglobulin purification in whey proteins. LWT, 49(1), 117–122. https://doi.org/10.1016/j.lwt.2012.03.022

11. Cimino, C. V., Colombo, M. L., Liggieri, C., Bruno, M., Vairo-Cavalli, S. (2015). Partial Molecular Characterization o Arctium minus Aspartyl Endopeptidase and Preparation of Bioactive Peptides by Whey Protein Hydrolysis. Journal of Medicinal Food, 18(8), 856–864. https://doi.org/10.1089/jmf.2014.0101

12. Daliri, E. B.-M., Lee, B. H., Park, B.-J., Kim, S.-H., Oh, D.-H. (2018). Antihypertensive peptides from whey proteins fermented by lactic acid bacteria. Food Science and Biotechnology, 27(6), 1781–1789. https://doi.org/10.1007/s10068-018-0423-0

13. de Castro, R. J. S., & Sato, H. H. (2014). Advantages of an acid protease from Aspergillus oryzae over commercial preparations for production of whey protein hydrolysates with antioxidant activities. Biocatalysis and Agricultural Biotechnology, 3(3), 58–65. https://doi.org/10.1016/j.bcab.2013.11.012

14. Donkor, O. N., Henriksson, A., Vasiljevic, T., Shah, N. P. (2007). Proteolytic activity of dairy lactic acid bacteria and probiotics as determinant of growth and in vitro angiotensin-converting enzyme inhibitory activity in fermented milk. Le Lait, 87(1), 21–38. https://doi.org/10.1051/lait:2006023

15. Farrokhi, F., Badii, F., Ehsani, M. R., & Hashemi, M. (2020). Effect of pH-dependent fibrillar structure on enzymatic hydrolysis and bioactivity of nanofibrillated whey protein. LWT, 131, 109709. https://doi.org/10.1016/j.lwt.2020.109709

16. Fernández-Fernández, A. M., Dumay, E., López-Pedemonte, T., Medrano-Fernandez, A. (2018). Bioaccessibility and cell metabolic activity studies of antioxidant low molecular weight peptides obtained by ultrafiltration of lactalbumin enzymatic hydrolysates. Food and Nutrition Sciences, 09(09), 1047–1065. https://doi.org/10.4236/fns.2018.99077

17. Fernández-Fernández, A. M., López-Pedemonte, T., Medrano-Fernandez, A. (2017). Evaluation of Antioxidant, Antiglycant and ACE-Inhibitory Activity in Enzymatic Hydrolysates of α-Lactalbumin. Food and Nutrition Sciences, 08(01), 84–98. https://doi.org/10.4236/fns.2017.81006

18. Gjorgievski, N., Tomovska, J., Dimitrovska, G., Makarjoski, B., Shariati, M.A. (2014). Determination of the antioxidant activity in yogurt. Journal of Hygienic Engineering and Design, 8, 67-73.

19. Gonzalez-Gonzalez, C., Gibson, T., Jauregi, P. (2013). Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20/5. International Journal of Food Microbiology, 167(2), 131–137. https://doi.org/10.1016/j.ijfoodmicro.2013.09.002

20. Gonzalez-Gonzalez, C. R., Tuohy, K. M., Jauregi, P. (2011). Production of angiotensin-I-converting enzyme (ACE) inhibitory activity in milk fermented with probiotic strains: Effects of calcium, pH and peptides on the ACE-inhibitory activity. International Dairy Journal, 21(9), 615–622. https://doi.org/10.1016/j.idairyj.2011.04.001

21. Guo, M. (2019). Whey protein production, chemistry, functionality, and applications.

22. Gútiez, L., Gómez-Sala, B., Recio, I., del Campo, R., Cintas, L. M., Herranz, C., Hernández, P. E. (2013). Enterococcus faecalis strains from food, environmental, and clinical origin produce ACE-inhibitory peptides and other bioactive peptides during growth in bovine skim milk. International Journal of Food Microbiology, 166(1), 93–101. https://doi.org/10.1016/j.ijfoodmicro.2013.06.019

23. Hafeez, Z., Cakir-Kiefer, C., Girardet, J.-M., Jardin, J., Perrin, C., Dary, A., Miclo, L. (2013). Hydrolysis of milk-derived bioactive peptides by cell-associated extracellular peptidases of Streptococcus thermophilus. Applied Microbiology and Biotechnology, 97(22), 9787–9799. https://doi.org/10.1007/s00253-013-5245-7

24. Hayes, M., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2007). Putting microbes to work: Dairy fermentation, cell factories and bioactive peptides. Part I: Overview. Biotechnology Journal, 2(4), 426–434. https://doi.org/10.1002/biot.200600246

25. Hebert, E. M., Mamone, G., Picariello, G., Raya, R. R., Savoy, G., Ferranti, P., Addeo, F. (2008). Characterization of the Pattern of α s1 - And β-Casein Breakdown and Release of a Bioactive Peptide by a Cell Envelope Proteinase from Lactobacillus delbrueckii subsp. lactis CRL 581. Applied and Environmental Microbiology, 74(12), 3682–3689. https://doi.org/10.1128/aem.00247-08

26. Hidalgo, M. E., Folmer Côrrea, A. P., Mancilla Canales, M., Joner Daroit, D., Brandelli, A., Risso, P. (2015). Biological and physicochemical properties of bovine sodium caseinate hydrolysates obtained by a bacterial protease preparation. Food Hydrocolloids, 43, 510–520. https://doi.org/10.1016/j.foodhyd.2014.07.009

27. Kamau, S. M., Lu, R.-R., Chen, W., Liu, X.-M., Tian, F.-W., Shen, Y., Gao, T. (2010). Functional significance of bioactive peptides derived from milk proteins. Food Reviews International, 26(4), 386–401. https://doi.org/10.1080/87559129.2010.496025

28. Korhonen, H. (2009). Milk-derived bioactive peptides: From science to applications. Journal of Functional Foods, 1(2), 177–187. https://doi.org/10.1016/j.jff.2009.01.007

29. Lacroix, I. M. E., & Li-Chan, E. C. Y. (2012). Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. International Dairy Journal, 25(2), 97–102. https://doi.org/10.1016/j.idairyj.2012.01.003

30. Le Maux, S., Nongonierma, A. B., Barre, C., FitzGerald, R. J. (2016). Enzymatic generation of whey protein hydrolysates under pH-controlled and non pH-controlled conditions: Impact on physicochemical and bioactive properties. Food Chemistry, 199, 246–251. https://doi.org/10.1016/j.foodchem.2015.12.021

31. Le Maux, S., Nongonierma, A. B., FitzGerald, R. J. (2017). Peptide composition and dipeptidyl peptidase IV inhibitory properties of β-lactoglobulin hydrolysates having similar extents of hydrolysis while generated using different enzyme-to-substrate ratios. Food Research International, 99, 84–90. https://doi.org/10.1016/j.foodres.2017.05.012

32. Le Maux, S., Nongonierma, A. B., Murray, B., Kelly, P. M., FitzGerald, R. J. (2015). Identification of short peptide sequences in the nanofiltration permeate of a bioactive whey protein hydrolysate. Food Research International, 77, 534–539. https://doi.org/10.1016/j.foodres.2015.09.012

33. Li-jun, L., Chuan-he, Z., & Zheng, Z. (2008). Analyzing molecular weight distribution of whey protein hydrolysates. Food and Bioproducts Processing, 86(1), 1–6. https://doi.org/10.1016/j.fБП.2007.10.007

34. López-Fandiño R., Otte J., Camp J. van (2006). Physiological, chemical and techno-logical aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity. International Dairy Journal, 11 (16), 1277–1293.

35. Lorenzetti, A., Penha, F. M., Cunha Petrus, J. C., Rezzadori, K. (2020). Low purity enzymes and ultrasound pretreatment applied to partially hydrolyze whey protein. Food Bioscience, 38, 100784. https://doi.org/10.1016/j.fbio.2020.100784

36. Madureira, A. R., Tavares, T., Gomes, A. M. P., Pintado, M. E., Malcata, F. X. (2010). Invited review: Physiological properties of bioactive peptides obtained from whey proteins. Journal of Dairy Science, 93(2), 437–455. https://doi.org/10.3168/jds.2009-2566

37. Mann, B., Athira, S., Sharma, R., Kumar, R., Sarkar, P. (2019). Bioactive peptides from whey proteins. In Whey Proteins (pp. 519–547). Elsevier. http://dx.doi.org/10.1016/b978-0-12-812124-5.00015-1

38. Mazorra-Manzano, M. A., Mora-Cortes, W. G., Leandro-Roldan, M. M., González-Velázquez, D. A., Torres-Llanez, M. J., Ramírez-Suarez, J. C., González-Córdova, A. F., Vallejo-Córdoba, B. (2020). Production of whey protein hydrolysates with angiotensin-converting enzyme-inhibitory activity using three new sources of plant proteases. Biocatalysis and Agricultural Biotechnology, 28, 101724. https://doi.org/10.1016/j.bcab.2020.101724

39. Mazorra-Manzano, M. A., Robles-Porchas, G. R., González-Velázquez, D. A., Torres-Llanez, M. J., Martínez-Porchas, M., García-Sifuentes, C. O., González-Córdova, A. F., Vallejo-Córdoba, B. (2020). Cheese whey fermentation by its native microbiota: Proteolysis and bioactive peptides release with ace-inhibitory activity. Fermentation, 6(1), 19. https://doi.org/10.3390/fermentation6010019

40. Miclo, L., Roux, É., Genay, M., Brusseaux, É., Poirson, C., Jameh, N., Perrin, C., & Dary, A. (2012). Variability of Hydrolysis of β-, αs1-, and αs2-Caseins by 10 Strains of Streptococcus thermophilus and Resulting Bioactive Peptides. Journal of Agricultural and Food Chemistry, 60(2), 554–565. https://doi.org/10.1021/jf202176d

41. Monari, S., Ferri, M., Russo, C., Prandi, B., Tedeschi, T., Bellucci, P., Zambrini, A. V., Donati, E., Tassoni, A. (2019). Enzymatic production of bioactive peptides from scotta, an exhausted by-product of ricotta cheese processing. PLOS ONE, 14(12), e0226834. https://doi.org/10.1371/journal.pone.0226834

42. Morais, H. A., Silvestre, M. P. C., Silva, M. R., Silva, V. D. M., Batista, M. A., Simões e Silva, A. C., Silveira, J. N. (2013). Enzymatic hydrolysis of whey protein concentrate: Effect of enzyme type and enzyme:substrate Ratio on peptide profile. Journal of Food Science and Technology, 52(1), 201–210. https://doi.org/10.1007/s13197-013-1005-z

43. Morales García, J., Herrera‐Rocha, F., Cavajalino, A. S., Duran Baron, R., González Barrios, A. F., Udenigwe, C. C. (2021). Effects of processing conditions on hydrolysates of proteins from whole whey and formation of Maillard reaction products. Journal of Food Processing and Preservation, 45(9). https://doi.org/10.1111/jfpp.15469

44. Naik, L., Mann, B., Bajaj, R., Sangwan, R. B., Sharma, R. (2013). Process optimization for the production of bio-functional whey protein hydrolysates: Adopting response surface methodology. International Journal of Peptide Research and Therapeutics, 19(3), 231–237. https://doi.org/10.1007/s10989-012-9340-x

45. Nongonierma, A. B., FitzGerald, R. J. (2017). Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins. Analytical and Bioanalytical Chemistry, 410(15), 3407–3423. https://doi.org/10.1007/s00216-017-0793-9

46. Nongonierma, A. B., Gaudel, C., Murray, B. A., Flynn, S., Kelly, P. M., Newsholme, P., FitzGerald, R. J. (2013). Insulinotropic properties of whey protein hydrolysates and impact of peptide fractionation on insulinotropic response. International Dairy Journal, 32(2), 163–168. https://doi.org/10.1016/j.idairyj.2013.05.014

47. Noren, N.E. (2015). Creation of a sticky coating of dairy proteins containing bioactive peptides to reduce dental caries.

48. Oh, N. S., Lee, J. Y., Oh, S., Joung, J. Y., Kim, S. G., Shin, Y. K., Lee, K.-W., Kim, S. H., Kim, Y. (2016). Improved functionality of fermented milk is mediated by the synbiotic interaction between Cudrania tricuspidata leaf extract and Lactobacillus gasseri strains. Applied Microbiology and Biotechnology, 100(13), 5919–5932. https://doi.org/10.1007/s00253-016-7414-y

49. O’Keeffe, M. B., FitzGerald, R. J. (2015). Identification of short peptide sequences in complex milk protein hydrolysates. Food Chemistry, 184, 140–146. https://doi.org/10.1016/j.foodchem.2015.03.077

50. Ortiz-Chao, P., Gómez-Ruiz, J. A., Rastall, R. A., Mills, D., Cramer, R., Pihlanto, A., Korhonen, H., Jauregi, P. (2009). Production of novel ACE inhibitory peptides from β-lactoglobulin using Protease N Amano. International Dairy Journal, 19(2), 69–76. https://doi.org/10.1016/j.idairyj.2008.07.011

51. Pa’ee, K. F., Gibson, T., Marakilova, B., Jauregi, P. (2015). Production of acid whey hydrolysates applying an integrative process: Effect of calcium on process performance. Process Biochemistry, 50(2), 302–310. https://doi.org/10.1016/j.procbio.2014.11.011

52. Panayotova, T., Pashova-Baltova, K., Dimitrov, Z. (2018). Production of ACE-inhibitory peptides in milk fermented with selected lactic acid bacteria. Journal of BioScience and Biotechnology. 7(1), 31-37.

53. Park, Y. W., Nam, M. S. (2015). Bioactive Peptides in Milk and Dairy Products: A Review. Korean journal for food science of animal resources, 35(6), 831–840. https://doi.org/10.5851/kosfa.2015.35.6.831

54. Pihlanto, A., Virtanen, T., Korhonen, H. (2010). Angiotensin I converting enzyme (ACE) inhibitory activity and antihypertensive effect of fermented milk. International Dairy Journal, 20(1), 3–10. https://doi.org/10.1016/j.idairyj.2009.07.003

55. Quirós, A., Ramos, M., Muguerza, B., Delgado, M. A., Miguel, M., Aleixandre, A., Recio, I. (2007). Identification of novel antihypertensive peptides in milk fermented with Enterococcus faecalis. International Dairy Journal, 17(1), 33–41. https://doi.org/10.1016/j.idairyj.2005.12.011

56. Quirós, A., Contreras, M. del M., Ramos, M., Amigo, L., Recio, I. (2009). Stability to gastrointestinal enzymes and structure–activity relationship of β-casein-peptides with antihypertensive properties. Peptides, 30(10), 1848–1853. https://doi.org/10.1016/j.peptides.2009.06.031

57. Raikos, V., Dassios, T. (2013). Health-promoting properties of bioactive peptides derived from milk proteins in infant food: A review. Dairy Science Technology, 94(2), 91–101. https://doi.org/10.1007/s13594-013-0152-3

58. Rasika, D., Ueda, T., Jayakody, L., Suriyagoda, L., Silva, K., Ando, S., Vidanarachchi, J. (2015). ACE-inhibitory activity of milk fermented with Saccharomyces cerevisiae K7 and Lactococcus lactis subsp. lactis NBRC 12007. Journal of the National Science Foundation of Sri Lanka, 43(2), 141. https://doi.org/10.4038/jnsfsr.v43i2.7942

59. Raveschot, C., Cudennec, B., Coutte, F., Flahaut, C., Fremont, M., Drider, D., Dhulster, P. (2018). Production of bioactive peptides by lactobacillus species: From gene to application. Frontiers in Microbiology, 9. https://doi.org/10.3389/fmicb.2018.02354

60. Robinson, R. C., Nielsen, S. D., Dallas, D. C., Barile, D. (2021). Can cheese mites, maggots and molds enhance bioactivity? Peptidomic investigation of functional peptides in four traditional cheeses. Food & Function, 12(2), 633–645. https://doi.org/10.1039/d0fo02439b

61. Rodríguez-Figueroa, J. C., González-Córdova, A. F., Torres-Llanez, M. J., Garcia, H. S., Vallejo-Cordoba, B. (2012). Novel angiotensin I-converting enzyme inhibitory peptides produced in fermented milk by specific wild Lactococcus lactis strains. Journal of Dairy Science, 95(10), 5536–5543. https://doi.org/10.3168/jds.2011-5186

62. Rossini, K., Noreña, C. P. Z., Cladera-Olivera, F., Brandelli, A. (2009). Casein peptides with inhibitory activity on lipid oxidation in beef homogenates and mechanically deboned poultry meat. LWT - Food Science and Technology, 42(4), 862–867. https://doi.org/10.1016/j.lwt.2008.11.002

63. Rubak, Y. T., Nuraida, L., Iswantini, D., Prangdimurti, E. (2020). Angiotensin-I-converting enzyme inhibitory peptides in milk fermented by indigenous lactic acid bacteria., Carpathian Journal of Food Science and Technology, 13(2), 345–353. https://doi.org/10.14202/vetworld.2020.345-353

64. Rubak, Y. T., Nuraida, L., Iswantini, D., Prangdimurti, E. (2019). Production of antihypertensive bioactive peptides in fermented food by lactic acid bacteria - a review. Carpathian Journal of Food Science and Technology, 11(4), 29-44. https://doi.org/10.34302/2019.11.4.3

65. Schalk, J. (2009). Optimization of the bioconvertion of the Angiotensin I Converting Enzyme inhibitors IPP and VPP. In Advances in Experimental Medicine and Biology. 275–276. Springer New York. http://dx.doi.org/10.1007/978-0-387-73657-0_123

66. Shi, M., Ahtesh, F., Mathai, M., McAinch, A. J., Su, X. Q. (2016). Effects of fermentation conditions on the potential anti-hypertensive peptides released from yogurt fermented by Lactobacillus helveticusand Flavourzyme®. International Journal of Food Science & Technology, 52(1), 137–145. https://doi.org/10.1111/ijfs.13253

67. Skrzypczak, K., Gustaw, W., Szwajgier, D., Fornal, E., Waśko, A. (2017). κ-Casein as a source of short-chain bioactive peptides generated by Lactobacillus helveticus. Journal of Food Science and Technology, 54(11), 3679–3688. https://doi.org/10.1007/s13197-017-2830-2

68. Subrota, H., Sreeja, V., Solanki, J., Prajapati, J.B. (2015). Significance of proteolytic microorganisms on ACE-inhibitory activity and release of bioactive peptides during fermentation of milk. Indian Journal of Dairy Science, 68(6), 584-591

69. Sultan, S., Huma, N., Butt, M. S., Aleem, M., Abbas, M. (2017). Therapeutic potential of dairy bioactive peptides: A contemporary perspective. Critical Reviews in Food Science and Nutrition, 58(1), 105–115. https://doi.org/10.1080/10408398.2015.1136590

70. Szwajkowska, M., Wolanciuk, A., Barłowska, J., Król, J., Litwińczuk, Z. (2011). Bovine milk proteins as the source of bioactive peptides influencing the consumers' immune system - a review. Animal Science Papers and Reports, 29(4), 269-280

71. Tavares, T., Contreras, M. del M., Amorim, M., Pintado, M., Recio, I., Malcata, F. X. (2011). Novel whey-derived peptides with inhibitory effect against angiotensin-converting enzyme: In vitro effect and stability to gastrointestinal enzymes. Peptides, 32(5), 1013–1019. https://doi.org/10.1016/j.peptides.2011.02.005

72. Tricco, A. C., Lillie, E., Zarin, W., O’Brien, K. K., Colquhoun, H., Levac, D., Moher, D., Peters, M. D. J., Horsley, T., Weeks, L., Hempel, S., Akl, E. A., Chang, C., McGowan, J., Stewart, L., Hartling, L., Aldcroft, A., Wilson, M. G., Garritty, C., Straus, S. E. (2018). PRISMA extension for scoping reviews (prisma-scr): Checklist and explanation. Annals of Internal Medicine, 169(7), 467–473. https://doi.org/10.7326/m18-0850

73. Tu, M., Liu, H., Zhang, R., Chen, H., Fan, F., Shi, P., Xu, X., Lu, W., Du, M. (2018). Bioactive hydrolysates from casein: Generation, identification, and in silico toxicity and allergenicity prediction of peptides. Journal of the Science of Food and Agriculture, 98(9), 3416–3426. https://doi.org/10.1002/jsfa.8854

74. Udenigwe, C., Abioye, R., Okagu, I.U., Joy, O.N. (2021). Bioaccessibility of bioactive peptides: recent advances and perspectives. Current Opinion in Food Science, 39, 182-189.

75. Ulug, S. K., Jahandidfh, F., Wu, J. (2021). Novel technologies for the production of bioactive peptides. Trends in Food Science, 108, 27–39. https://doi.org/10.1016/j.tifs.2020.12.002

76. Venegas‐Ortega, M. G., Flores‐Gallegos, A. C., Martínez‐Hernández, J. L., Aguilar, C. N., Nevárez‐Moorillón, G. V. (2019). Production of bioactive peptides from lactic acid bacteria: A sustainable approach for healthier foods. Comprehensive Reviews in Food Science and Food Safety, 18(4), 1039–1051. https://doi.org/10.1111/1541-4337.12455

77. Villadóniga, C., Macció, L., Cantera, A. M. B. (2018). Acid whey proteolysis to produce angiotensin-I converting enzyme inhibitory hydrolyzate. Environmental Sustainability, 1(3), 267–278. https://doi.org/10.1007/s42398-018-0027-x

78. Vicente, C.M.R.R.S. (2008). Valorisation of the Peptidic Fraction of Cheese Whey.

79. Wakai, T., Yamaguchi, N., Hatanaka, M., Nakamura, Y., Yamamoto, N. (2012). Repressive processing of antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro, in Lactobacillus helveticus fermented milk by added peptides. Journal of Bioscience and Bioengineering, 114(2), 133–137. https://doi.org/10.1016/j.jbiosc.2012.03.015

80. Worsztynowicz, P., Białas, W., & Grajek, W. (2020). Integrated approach for obtaining bioactive peptides from whey proteins hydrolysed using a new proteolytic lactic acid bacterium. Food Chemistry, 312, 126035. https://doi.org/10.1016/j.foodchem.2019.126035