A novel five-amino-acid peptide (IDYRY) isolated from the microalga Chlamydomonas reinhardtii lowered blood pressure in hypertensive rats through a unique binding mechanism distinct from existing ACE inhibitors like captopril.
IC50 = 18.54 μMACE inhibitory potency of the novel microalgal peptide IDYRY — the first ACE-inhibitory peptide discovered from Chlamydomonas reinhardtii
What the researchers found
From eight protease hydrolysates of Chlamydomonas reinhardtii, the alkaline protease hydrolysate (CRPA) showed the strongest ACE inhibitory activity. The first ACE-inhibitory peptide identified from this microalga — a five-amino-acid sequence called IDYRY (ID-5) — had an IC50 of 18.54 ± 5.57 μM.
ID-5 was characterized as a noncompetitive ACE inhibitor, meaning it binds to the enzyme at a different site than the substrate. It demonstrated significant antihypertensive activity both in vitro and in spontaneously hypertensive rats (SHRs), with an effective dose corresponding to a human-equivalent dose of approximately 16 mg/kg/day. Molecular dynamics simulations revealed that ID-5 forms unique hydrogen bonds with Asp415 and Arg522 on ACE, a binding mechanism distinct from captopril or lisinopril.
Why it matters
ACE inhibitors are among the most widely prescribed medications for high blood pressure, but they can cause side effects like dry cough and angioedema. Discovering a food-derived peptide that inhibits ACE through a completely different binding mechanism opens the door to new therapeutic approaches with potentially different side effect profiles. Additionally, sourcing bioactive peptides from microalgae — which can be cultivated sustainably — aligns with growing interest in sustainable functional food ingredients.
How the study worked
Researchers prepared eight different protease hydrolysates from Chlamydomonas reinhardtii protein. ACE inhibitory activity was screened in vitro, and the most potent hydrolysate was tested in vivo using spontaneously hypertensive rats (SHRs). Bioassay-guided fractionation was used to isolate the active peptide. The peptide's binding mechanism was characterized through molecular docking and molecular dynamics simulation, and its inhibition type (noncompetitive) was determined through enzyme kinetics.
What this study cannot tell us
The antihypertensive effect was demonstrated only in spontaneously hypertensive rats, not in humans. The IC50 value of 18.54 μM is moderate compared to pharmaceutical ACE inhibitors. Oral bioavailability, gastrointestinal stability, and absorption of the peptide in humans are unknown. The human-equivalent dose is an estimate based on animal scaling and has not been validated clinically. Molecular dynamics simulations model binding in silico and may not perfectly reflect in vivo conditions.
How to read the evidence
This study combines in vitro enzyme assays, in vivo animal testing in hypertensive rats, and computational modeling, providing multi-level preclinical evidence. However, there are no human data, and the peptide's oral bioavailability is uncharacterized.
When this study was published
Published in 2026, this is a very recent discovery representing the cutting edge of microalgae-derived bioactive peptide research.
The bigger picture
This study sits at the intersection of two growing fields: food-derived bioactive peptides and sustainable microalgal biotechnology. While numerous ACE-inhibitory peptides have been discovered from milk, fish, and plant sources, microalgae remain relatively untapped. The unique noncompetitive binding mechanism distinguishes this peptide from known inhibitors and could inspire new drug design. As microalgae are already being developed as sustainable protein sources, identifying high-value bioactive peptides within them adds economic and health value to algal farming.
Questions still open
- Does the IDYRY peptide survive human digestion intact and reach the bloodstream at effective concentrations?
- How does the antihypertensive potency of this microalgal peptide compare to established food-derived ACE inhibitors from milk or fish sources?
- Could the noncompetitive binding mechanism of ID-5 reduce the side effects commonly seen with traditional ACE inhibitors?
Common questions
What is Chlamydomonas reinhardtii and why are scientists looking for peptides in it?
How is this peptide different from existing blood pressure medications?
Read the original research
Discovery and molecular mechanism of a novel antihypertensive peptide from Chlamydomonas reinhardtii based on molecular docking, molecular dynamics simulation, in vitro, and in vivo analysis.
Food research international (Ottawa, Ont.), 229, 118477
Citation
Suo, Qishan; Yue, Yang; Wang, Jing; Wu, Ning; Geng, Lihua; Zhang, Quanbin. (2026). Discovery and molecular mechanism of a novel antihypertensive peptide from Chlamydomonas reinhardtii based on molecular docking, molecular dynamics simulation, in vitro, and in vivo analysis.. Food research international (Ottawa, Ont.), 229, 118477. https://doi.org/10.1016/j.foodres.2026.118477