Natural ACE inhibitory peptides discovery from Spirulina (Arthrospira platensis) strain C1

Krittima Anekthanakul; Jittisak Senachak; Apiradee Hongsthong; Tossaton Charoonratana; Marasri Ruengjitchatchawalya

doi:10.1016/j.peptides.2019.170107

Natural ACE inhibitory peptides discovery from Spirulina (Arthrospira platensis) strain C1

Peptides. 2019 Aug:118:170107. doi: 10.1016/j.peptides.2019.170107. Epub 2019 Jun 20.

Authors

Krittima Anekthanakul¹, Jittisak Senachak², Apiradee Hongsthong², Tossaton Charoonratana³, Marasri Ruengjitchatchawalya⁴

Affiliations

¹ Biotechnology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Thailand.
² Biosciences and Systems Biology Research Team, Biochemical Engineering and Systems Biology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at King Mongkut's University of Technology Thonburi, Thailand.
³ Department of Pharmacognosy, College of Pharmacy, Rangsit University, Thailand.
⁴ Biotechnology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Thailand; Bioinformatics and Systems Biology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Thailand. Electronic address: marasri.rue@kmutt.ac.th.

PMID: 31229668
DOI: 10.1016/j.peptides.2019.170107

Abstract

Bioactive peptides from natural sources are utilized as food supplements for disease prevention and are increasingly becoming targets for drug discovery due to their specificity, efficacy and the absence of undesirable side effects, among others. Hence, the 'SpirPep' platform was developed to facilitate the in silico-based bioactive peptide discovery of these highly sought-after biomolecules from Spirulina(Arthrospira platensis) and to select the protease (thermolysin) used for in vitro digestion. Analysis of the predicted and experimentally-derived peptides suggested that they were mainly involved in ACE inhibition; thus, an ACEi assay was used to study the ACE inhibitory activity of five candidate peptides (SpirPep1-5), chosen from common peptides with multifunctional bioactivity and 100% bioactive peptide coverage, originating from phycobiliproteins. Results showed that SpirPep1 inhibited the activity of ACE with IC₅₀ of 1.748 mM and was non-toxic to fibroblasts of African green monkey kidney and human dermal skin. The molecular docking and MD simulation analysis revealed SpirPep1 had significantly lower binding scores than others and showed greater specificity to ACE. The non-bonded interaction energy of SpirPep1 and ACE was -883 kJ/mol. The SpirPep1 indirectly bound to ACE via the ACE substrate binding sites residues (D121, E123, S516, and S517) found in natural ACE inhibitory peptides (angiotensin II and bradykinin potentiating peptides). In addition, two unreported substrate binding sites including R124 and S219 were found. These results indicate that 'SpirPep' platform could increase the success rate for natural bioactive peptide discovery.

Keywords: Angiotensin I converting enzyme; Arthrospira platensis; Molecular docking; Molecular dynamic; SpirPep; Spirulina.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Angiotensin-Converting Enzyme Inhibitors / chemistry*
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Binding Sites
Molecular Docking Simulation
Peptides / chemistry*
Spirulina / chemistry*

Substances

Angiotensin-Converting Enzyme Inhibitors
Peptides