Production of angiotensin-I-converting enzyme inhibitory peptides from β-lactoglobulin- and casein-derived peptides: an integrative approach

Biotechnol Prog. May-Jun 2012;28(3):746-55. doi: 10.1002/btpr.1541. Epub 2012 May 21.


Angiotensin I-converting enzyme (ACE) inhibition is one of the mechanisms by which reduction in blood pressure is exerted. Whey proteins are a rich source of ACE inhibitory peptides and have shown a blood pressure reduction effect i.e. antihypertensive activity. The aim of this work was to develop a simplified process using a combination of adsorption and microfiltration steps for the production of hydrolysates from whey with high ACE inhibitory activity and potency; the latter was measured as the IC50, which is the peptide concentration required to reduce ACE activity by half. This process integrates the selective separation of β-lactoglobulin- and casein-derived peptides (CDP) from rennet whey and their hydrolysis, which results in partially pure, less complex hydrolysates with high bioactive potency. Hydrolysis was carried out with protease N "Amano" in a thermostatically controlled membrane reactor operated in a batch mode. By applying the integrative approach it was possible to produce from the same feedstock two different hydrolysates that exhibited high ACE inhibition. One hydrolysate was mainly composed of casein-derived peptides with IC50=285 μg/mL. In this hydrolysate we identified the well-known potent ACE-inhibitor and antihypertensive tripeptide Ile-Pro-Pro (IPP) and another novel octapeptide Gln-Asp-Lys-Thr-Glu-Ile-Pro-Thr (QDKTEIPT). The second hydrolysate was mainly composed of β-lactoglobulin derived peptides with IC50=28 μg/mL. This hydrolysate contained a tetrapeptide (Ile-Ile-Ala-Glu) IIAE as one of the two major peptides. A further advantage to this process is that enzyme activity was substantially increased as enzyme product inhibition was reduced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Caseins / chemistry*
  • Chromatography, High Pressure Liquid
  • Hydrolysis
  • Lactoglobulins / chemistry*
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / pharmacology
  • Peptide Hydrolases / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry


  • Angiotensin-Converting Enzyme Inhibitors
  • Caseins
  • Lactoglobulins
  • Peptide Fragments
  • Peptide Hydrolases