Food Science and Biotechnology

, Volume 27, Issue 6, pp 1781–1789 | Cite as

Antihypertensive peptides from whey proteins fermented by lactic acid bacteria

  • Eric Banan-Mwine Daliri
  • Byong H. Lee
  • Byun-Jae Park
  • Se-Hun Kim
  • Deog-Hwan Oh


In this study, whey proteins were fermented with 34 lactic acid bacteria for 48 h at 37 °C and their ability to inhibit angiotensin 1-converting enzyme (ACE) activity were compared. All the lactic acid bacteria displayed varying proteolytic abilities in whey. Their fermentates also displayed varying abilities to inhibit ACE in vitro. Seven fermentates showed strong ACE inhibitory abilities between 84.70 ± 0.67 and 52.40 ± 2.1% with IC50 values between 19.78 ± 1.73 and 2.13 ± 0.7 mg/ml. Pediococcus acidilactici SDL1414 showed the strongest ACE inhibitory activity of 84.7 ± 0.67% (IC50 = 19.78 ± 1.73 μg/ml). Mass spectrometry revealed that more than half (57.7%) of the low molecular weight peptides (< 7 kDa) in the P. acidilactici SDL1414 fermented samples were ACE inhibitory peptides. Our results show that P. acidilactici SDL1414 could be used as a starter culture in the dairy industry to develop antihypertensive functional foods for hypertension management.


Fermentates Angiotensin1-converting enzyme Bioactive peptides 



This work was funded by the Ministry of Small and Medium scale Enterprises and Startups. Grant Number C0502529. We also thank the central laboratory of Kangwon National University for their assistance in LC-MS analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abdel-Hamid M, Otte J, De Gobba C, Osman A, Hamad E. Angiotensin I-converting enzyme inhibitory activity and antioxidant capacity of bioactive peptides derived from enzymatic hydrolysis of buffalo milk proteins. Int Dairy J. 66:91–98 (2017)CrossRefGoogle Scholar
  2. Ahn J, Park S, Atwal A, Gibbs B, Lee B. Angiotensin I‐converting enzyme (ACE) inhibitory peptides from whey fermented by Lactobacillus species. J Food Biochem. 33:587–602 (2009)CrossRefGoogle Scholar
  3. Bounouala FZ, Roudj S, Karam N-E, Recio I, Miralles B. Casein hydrolysates by Lactobacillus brevis and Lactococcus lactis proteases. Peptide profile discriminates strain-dependent enzyme specificity. J. Agric. Food Chem. 65: 9324–9332 (2017)CrossRefGoogle Scholar
  4. Brzozowski B, Lewandowska M. Prolyl endopeptidase-Optimization of medium and culture conditions for enhanced production by Lactobacillus acidophilus. Electron J Biotechnol.17:204–210 (2014)CrossRefGoogle Scholar
  5. Chang OK, Roux É, Awussi AA, Miclo L, Jardin J, Jameh N, Dary A, Humbert G, Perrin C. Use of a free form of the Streptococcus thermophilus cell envelope protease PrtS as a tool to produce bioactive peptides. Int Dairy J. 38:104–115 (2014)CrossRefGoogle Scholar
  6. Church FC, Swaisgood HE, Porter DH, Catignani GL. Spectrophotometric assay using O-phthaldialdehyde for determination of proteolysis in milk and isolated milk proteins. J Dairy Sci. 66:1219–1227 (1983)CrossRefGoogle Scholar
  7. Cushman D, Cheung H. Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem. Pharmacol. 20:1637–1648 (1971)CrossRefGoogle Scholar
  8. Daliri EB-M, Oh DH, Lee BH. Bioactive peptides. Foods 6:32–42 (2017a)CrossRefGoogle Scholar
  9. Daliri EB-M, Lee BH, Oh DH. Current trends and perspectives of bioactive peptides. Crit. Rev. Food. Sci. Nutr. (2017b). CrossRefPubMedGoogle Scholar
  10. Daliri EB-M, Lee BH, Oh DH. Current perspectives on antihypertensive probiotics. Probiotics Antimicro Prot. 9:91–101 (2017c)CrossRefGoogle Scholar
  11. Georgalaki M, Zoumpopoulou G, Mavrogonatou E, Van Driessche G, Alexandraki V, Anastasiou R, Papadelli M, Kazou M, Manolopoulou E, Kletsas D, Devreese B. Evaluation of the antihypertensive angiotensin-converting enzyme inhibitory (ACE-I) activity and other probiotic properties of lactic acid bacteria isolated from traditional Greek dairy products. Int Dairy J. 75:10–21 (2017)CrossRefGoogle Scholar
  12. Griffiths MW, Tellez AM. Lactobacillus helveticus: the proteolytic system. Front Microbiol. 4:30 (2013). CrossRefPubMedPubMedCentralGoogle Scholar
  13. Ha GE, Chang OK, Jo S-M, Han G-S, Park B-Y, Ham J-S, Jeong S-G. Identification of antihypertensive peptides derived from low molecular weight casein hydrolysates generated during fermentation by Bifidobacterium longum KACC 91563. Korean J Food Sci Anim Resour. 35:738 (2015)CrossRefGoogle Scholar
  14. Hayes M, Stanton C, Slattery H, O’Sullivan O, Hill C, Fitzgerald G, Ross R. Casein fermentate of Lactobacillus animalis DPC6134 contains a range of novel propeptide angiotensin-converting enzyme inhibitors. Appl. Environ. Microbiol. 73:4658–4667 (2007)CrossRefGoogle Scholar
  15. Ibrahim HR, Ahmed AS, Miyata T. Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk. J. Adv. Res. 8:63–71 (2017)CrossRefGoogle Scholar
  16. Jauhiainen T, Rönnback M, Vapaatalo H, Wuolle K, Kautiainen H, Groop P, Korpela R. Long-term intervention with Lactobacillus helveticus fermented milk reduces augmentation index in hypertensive subjects. Eur J Clin Nutr. 64: 424–431 (2010)CrossRefGoogle Scholar
  17. Jin Y, Yu Y, Qi Y, Wang F, Yan J, Zou H. Peptide profiling and the bioactivity character of yogurt in the simulated gastrointestinal digestion. J. Proteom. 141:24–46 (2016)CrossRefGoogle Scholar
  18. Juillard V, Laan H, Kunji E, Jeronimus-Stratingh CM, Bruins AP, Konings WN. The extracellular PI-type proteinase of Lactococcus lactis hydrolyzes beta-casein into more than one hundred different oligopeptides. J. Bacteriol. 177:3472–3478 (1995)CrossRefGoogle Scholar
  19. Kaspari A, Diefenthal T, Grosche G, Schierhorn A, Demuth H-U. Substrates containing phosphorylated residues adjacent to proline decrease the cleavage by proline-specific peptidases. Biochim Biophys Acta Protein Struct Molec Enzym. 1293:147–153 (1996)CrossRefGoogle Scholar
  20. Koyama M, Hattori S, Amano Y, Watanabe M, Nakamura K. Blood pressure-lowering peptides from neo-fermented buckwheat sprouts: a new approach to estimating ACE-inhibitory activity. PloS one. 9:e105802 (2014)CrossRefGoogle Scholar
  21. Kumar R, Chaudhary K, Sharma M, Nagpal G, Chauhan JS, Singh S, Gautam A, Raghava GP. AHTPDB: a comprehensive platform for analysis and presentation of antihypertensive peptides. Nucleic acids research. 43:D956-D62 (2014)CrossRefGoogle Scholar
  22. Liu M, Bayjanov JR, Renckens B, Nauta A, Siezen RJ. The proteolytic system of lactic acid bacteria revisited: a genomic comparison. BMC genomics. 11:36 (2010)CrossRefGoogle Scholar
  23. Manzanares P, Salom JB, García-Tejedor A, Fernández-Musoles R, Ruiz-Giménez P, Gimeno-Alcañíz JV. Unraveling the mechanisms of action of lactoferrin-derived antihypertensive peptides: ACE inhibition and beyond. Food & function. 6:2440–52 (2015)CrossRefGoogle Scholar
  24. Miclo L, Roux Em, Genay M, Brusseaux Em, Poirson C, Jameh N, Perrin C, Dary A. Variability of hydrolysis of β-, αs1-, and αs2-caseins by 10 strains of Streptococcus thermophilus and resulting bioactive peptides. J. Agric. Food Chem. 60:554–565 (2012)CrossRefGoogle Scholar
  25. Minkiewicz P, Dziuba J, Iwaniak A, Dziuba M, Darewicz M. BIOPEP database and other programs for processing bioactive peptide sequences. J. AOAC Int. 91:965–980 (2008)PubMedPubMedCentralGoogle Scholar
  26. Nagpal R, Behare P, Rana R, Kumar A, Kumar M, Arora S, Morotta F, Jain S, Yadav H. Bioactive peptides derived from milk proteins and their health beneficial potentials: an update. Food & function. 2:18–27 (2011)CrossRefGoogle Scholar
  27. Nakamura K, Naramoto K, Koyama M. Blood-pressure-lowering effect of fermented buckwheat sprouts in spontaneously hypertensive rats. J Funct Foods.5:406–415 (2013)CrossRefGoogle Scholar
  28. Nakamura Y, Yamamoto N, Sakai K, Takano T. Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J Dairy Sci. 78:1253–1257 (1995)CrossRefGoogle Scholar
  29. Oh NS, Lee JY, Oh S, Joung JY, Kim SG, Shin YK, Lee K-W, Kim SH, Kim Y. Improved functionality of fermented milk is mediated by the synbiotic interaction between Cudrania tricuspidata leaf extract and Lactobacillus gasseri strains. Appl Microbiol Biotechnol. 100:5919-5932 (2016)CrossRefGoogle Scholar
  30. Sánchez A, Vázquez A. Bioactive peptides: A review. Food Quality Safety.1:29–46 (2017)CrossRefGoogle Scholar
  31. Svanborg S, Johansen A-G, Abrahamsen RK, Schüller RB, Skeie SB. Caseinomacropeptide influences the functional properties of a whey protein concentrate. Int Dairy J. 60:14–23 (2016)CrossRefGoogle Scholar
  32. Tavares T, del Mar Contreras M, Amorim M, Pintado M, Recio I, Malcata FX. Novel whey-derived peptides with inhibitory effect against angiotensin-converting enzyme: in vitro effect and stability to gastrointestinal enzymes. Peptides. 32:1013–1019 (2011)CrossRefGoogle Scholar
  33. Torres-Llanez M, González-Córdova A, Hernandez-Mendoza A, Garcia H, Vallejo-Cordoba B. Angiotensin-converting enzyme inhibitory activity in Mexican Fresco cheese. J Dairy Sci. 94:3794–800 (2011)CrossRefGoogle Scholar
  34. Tsakalidou E, Anastasiou R, Vandenberghe I, Van Beeumen J, Kalantzopoulos G. Cell-wall-bound proteinase of Lactobacillus delbrueckii subsp. lactis ACA-DC 178: characterization and specificity for β-casein. Appl. Environ. Microbiol. 65:2035–2040 (1999)PubMedPubMedCentralGoogle Scholar
  35. Zahraa N. Le peptide κ-CN (f106-109) du lait: propriétés nutritionnelles, biologiques et techno-fonctionnelles. Mémoire de M2 UHP Nancy 1, France (2010)Google Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Eric Banan-Mwine Daliri
    • 1
  • Byong H. Lee
    • 1
    • 2
  • Byun-Jae Park
    • 1
  • Se-Hun Kim
    • 1
  • Deog-Hwan Oh
    • 1
  1. 1.Department of Food Science and BiotechnologyKangwon National UniversityChuncheonSouth Korea
  2. 2.Department of Food Science/Agricultural ChemistryMcGill UniversitySte-Anne-de-BellevueCanada

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