High Throughput Identification of Antihypertensive Peptides from Fish Proteome Datasets

Abstract

Antihypertensive peptides (AHTPs) are a group of small peptides with the main role to block key enzymes or receptors in the angiotensin genesis pathway. A great number of AHTPs have been isolated or digested from natural food resources; however, comprehensive studies on comparisons of AHTPs in various species from the perspective of big data are rare. Here, we established a simplified local AHTP database, and performed in situ mapping for high throughput identification of AHTPs with high antihypertensive activity from high-quality whole proteome datasets of 18 fish species. In the 35 identified AHTPs with reported high activity, we observed that Gly-Leu-Pro, Leu-Pro-Gly, and Val-Ser-Val are the major components of fish proteins, and AHTP hit numbers in various species demonstrated a similar distributing pattern. Interestingly, Atlantic salmon (Salmo salar) is in possession of far more abundant AHTPs compared with other fish species. In addition, collagen subunit protein is the largest group with more matching AHTPs. Further exploration of two collagen subunits (col4a5 and col8a1) in more fish species suggested that the hit pattern of these conserved proteins among teleost is almost the same, and their phylogeny is consistent with the evolution of these fish species. In summary, our present study provides basic information for the relationship of AHTPs with fish proteins, which sheds light on rapid discovery of marine drugs or food additives from fish protein hydrolysates to alleviate hypertension.

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

“…This point of view, although concerns the peptide QSAR modeling, can also refer to the possible differences between the theoretical (e.g., PeptideRanker Score) and experimental bioactivity of a peptide (e.g., IC 50 value). Therefore, some authors postulate unifying the concentration units when determining the inhibitory activity and establishing a standard procedure to construct an updated real-time database [61].…”

The First Genome Survey of the Antarctic Krill (Euphausia superba) Provides a Valuable Genetic Resource for Polar Biomedical Research

“…The Involucrin with the most abundant AHTPs is a keratinocyte protein [45], and keratinocytes is the major constituent of the epidermis tissue [46] of the skin's outer layer [47]. As for the whiteleg shrimp, however, both collagen alpha-1(V) chain-like protein and collagen alpha-1(XI) chain-like protein were the most abundant AHTP-containing proteins, which were revealed previously by us in fishes [13]. In fact, ACE-inhibitory peptides had been obtained from the collagen hydrolysates of many animals [48][49][50][51][52][53].…”

“…To identify potential AHTPs in the translated proteomes (from the genome or transcriptome data) of the Antarctic krill and the whiteleg shrimp, we built a local AHTP-searching database [13]. Most of the known AHTPs searched in this database have been verified in reported studies, and they are usually tripeptides with less than 10 amino acids; the top 50 AHTPs with the highest activity were chosen to identify AHTPs in the two crustacean species, as reported in our previous study [14].…”

“…The AHTPs with the top 50 inhibitory activities were compiled as a local searching reference as described in our previous study [13]. Employing a local custom Perl script pipeline, we identified matched AHTPs sequences and locations from target proteins in the transcriptomes of E. superba [1] and P. vannamei [24], as well as the genome of P. vannamei [8].…”

“…Angiotensin converting enzyme (ACE) inhibitors are preferred antihypertensive drugs, and antihypertensive peptides (AHTPs), another important representative with short sequences, are the most effective and popularly studied ACE inhibitory peptides [13]. A lot of AHTPs are usually digested from natural products, and they most frequently contain 2~10 amino acids.…”