Novel Angiotensin-Converting Enzyme-Inhibitory Peptides From Fermented Bovine Milk Started by Lactobacillus helveticus KLDS.31 and Lactobacillus casei KLDS.105: Purification, Identification, and Interaction Mechanisms

Abstract

Fermented milks with strong angiotensin I-converting enzyme (ACE)-inhibitory activity were obtained through a culture with Lactobacillus helveticus KLDS.31 and Lactobacillus casei KLDS.105 with a fermentation and storage temperature of 37 °C. Ultrafiltration fractions with a molecular weight less than 3 kDa in fermented milk whey exhibited the strongest inhibitory activity. Correspondingly, a gastrointestinal digestion experiment showed retention of the bioactivity of these fractions with pepsin and trypsin treatment. Four ACE-inhibitory peptides from fermented milk were isolated, purified by two-step reverse chromatography, and sequenced. Furthermore, the interaction mechanisms between ACE and four isolated peptides were investigated by a molecular docking method and the Independent Gradient Model. Experimental determination of IC50 was done to verify theoretical results. The inhibitory peptide interacted with ACE as follows: Lys-Pro-Ala-Gly-Asp-Phe > Lys-Ala-Ala-Leu-Ser-Gly-Met > Lys-Lys-Ala-Ala-Met-Ala-Met > Leu-Asp-His-Val-Pro-Gly-Gly-Ala-Arg.

Lacticaseibacillus paracasei DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells

“…41 Some lactobacilli have been reported to release peptides with high affinity for ACE during milk fermentation. 42 Although the mechanism supporting the antiviral activity of L. paracasei DG observed in this study is not known, we can speculate that the unique rhamnose-rich heteroexopolysaccharide molecule that covers the cells of this bacterium may contribute to the peculiar cross-talk of DG with host cells. 43 Indeed, a limitation of our study was the inability to determine the essential molecules produced by L. paracasei DG required to inhibit SARS-CoV-2 replication.…”

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects

“…For instance, during milk fermentation, Lactobacillus helveticus and Lactobacillus casei release peptides with high affinity for ACE. Bovine milk fermented with Lactobacillus species yields fermented products enriched with ACE-inhibitory peptides ( 66 ), of which many are resistant to GI digestion and inhibit ACE in the renin-angiotensin system (RAS). In vitro and in vivo experiments have demonstrated antihypertensive effects of fermented milk products ( 67 , 68 ).…”

Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic

“…Laboratory studies have reported that certain probiotics have anti-viral effects including against other forms of coronavirus ( Chai et al, 2013 ). Others have reported the potential of probiotics to interact with ACE2, the host entry receptor of SARS-CoV-2 virus; for instance, some lactobacilli have been reported to release peptides with high affinity for ACE during milk fermentation ( Li et al, 2019 ). Recently, Paenibacillus bacteria were shown to naturally produce carboxypeptidases homologous to ACE2 in structure and function ( Minato et al, 2020 ).…”