CN115109117A - Multicladium algae phycoerythrin angiotensin converting enzyme inhibitory peptide and preparation method and application thereof - Google Patents
Multicladium algae phycoerythrin angiotensin converting enzyme inhibitory peptide and preparation method and application thereof Download PDFInfo
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- CN115109117A CN115109117A CN202210968563.4A CN202210968563A CN115109117A CN 115109117 A CN115109117 A CN 115109117A CN 202210968563 A CN202210968563 A CN 202210968563A CN 115109117 A CN115109117 A CN 115109117A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
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- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A61K38/00—Medicinal preparations containing peptides
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Abstract
The invention belongs to the technical field of bioactive peptide protein, and relates to a multicystis algae phycoerythrin angiotensin converting enzyme inhibitory peptide, a preparation method and application thereof. The amino acid sequence of the peptide is shown as SEQ ID NO.1, and the amino acid sequence of the peptide is Phe-Phe-Lys-Ala (FFKA). The invention screens and obtains the unreported small peptide FFKA capable of effectively inhibiting the activity of angiotensin converting enzyme from the phycoerythrin of multiclada for the first time, and defines the structure of the small peptide FFKA, and the FFKA has the advantages of safety and no toxicity, so the FFKA has good application prospect when being used as a functional component in foods, health care products and blood pressure lowering medicines.
Description
Technical Field
The invention belongs to the technical field of bioactive peptide proteins, and particularly relates to a multicladium alga phycoerythrin angiotensin converting enzyme inhibitory peptide, and a preparation method and application thereof.
Background
At present, hypertension is a common frequently encountered disease in human beings. According to statistics, the average prevalence rate of hypertension in various countries in the world is 10% -12%. The number of hypertension patients in China exceeds 1.2 hundred million. Hypertension seriously affects human health and quality of life. According to WHO reports that over 1750 million people die of cardiovascular diseases each year worldwide. Cardiovascular disease has been globally recognized as a major cause of human death. In recent years, there has been a trend toward an increase in cardiovascular diseases year by year. Hypertension is one of the significant risk factors for cardiovascular disease, with typical characteristics of age-related diseases. Chronic renal failure, stroke, etc. are also caused by persistent hypertension. Therefore, the development of hypertension prevention and treatment medicines is of great significance.
Angiotensin Converting Enzyme (ACE) is a key enzyme in the human body that regulates the renin-angiotensin system and the kinin-bradykinin system, and ACE can convert angiotensin I into angiotensin II, causing vasoconstriction and indirectly causing blood pressure to rise. Inhibiting the activity of ACE can lower blood pressure. ACE is therefore an important target for the treatment of hypertension.
At present, more than 20 ACE inhibitors clinically used for treating hypertension are synthesized by chemical synthesis. The commercially available chemically synthesized antihypertensive drugs (such as captopril and the like) achieve the antihypertensive effect by inhibiting the activity of ACE, and generally have obvious toxic and side effects, such as dizziness, renal dysfunction, hyperkalemia, cough, skin pruritus, taste disturbance or hypotension and the like. Therefore, the development of a novel antihypertensive drug which is safe and has no toxic or side effect is necessary.
ACE inhibitory peptides are polypeptides with ACE inhibitory activity, have molecular weight usually less than 3KDa, and are widely used for preventing and treating hypertension. Compared with chemical synthesis ACE inhibitors, the ACE inhibitory peptide has the advantages of being natural, good in water solubility, safe, free of toxic and side effects and the like, and can be used as functional food, health care products, medicines and the like for reducing blood pressure.
At present, various peptides with ACE (angiotensin converting enzyme) inhibiting activity are screened and identified from ulva, chlorella, laver, spirulina platensis and volutes perli. In vitro ACE inhibitory activity IC of IVWDMEK and VGPAGERPG 50 2.08mM and 4.66mM, respectively. Also, ACE inhibitory peptides AILAGDPSVLEDR and VVGGTGPVDEWGIAGAR of red algae, ACE inhibitory peptides YRD and LDY of Palmaria palmata, ACE inhibitory peptide LF of Porphyra japonica, ACE inhibitory peptide VY of Undaria pinnatifida, ACE inhibitory peptide TYA of Porphyra, ACE inhibitory peptide VTY of Porphyra japonica, and LGVP.
Polysiphonia urceolata (Polysiphonia urceolata) is a higher red alga of the order Euerythrophyceae, order Dictyotales, family Arthrodinaceae. The wild multicladium aquaticum raw material in coastal areas of China is rich, and the wild multicladium aquaticum enters a breeding period in 3-5 months. Polysiphonia urceolata is rich in phycobiliproteins and other bioactive components. Phycobiliproteins of multiclada comprise three kinds of Phycoerythrin (R-Phytoerythrothrin, R-PE), Phycoerythrin and allophycocyanin, wherein the Phycoerythrin is trimodal Phycoerythrin and has a hexamer structure, good water solubility, stable property and bright fluorescence, and the absorbance at 488nm is higher than that of B-PE, so that the Phycoerythrin is excellent pigment protein, fluorescent marker and medicine. The multicladium has high R-PE content and low polysaccharide (i.e. phycocolloid) content, so that the separation and purification efficiency of R-PE is high, and the multicladium also becomes a main algae material for R-PE preparation and research. The multicladium algae phycoerythrin has high biological activity and has various biological functions of reducing blood pressure, resisting oxidation, inflammation, viruses, aging, radiation, tumors and the like, so the multicladium algae phycoerythrin is an excellent protein raw material for screening bioactive peptides. Currently, there is less research on ACE inhibitory peptides from multicladium.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides an angiospermum erythroprotein angiotensin-converting enzyme inhibitory peptide, a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the application provides a multiclada phycoerythrin angiotensin converting enzyme inhibitory peptide, wherein the amino acid sequence of the peptide is shown in SEQ ID No. 1.
The amino acid sequence of the multicladus alga phycoerythrin angiotensin converting enzyme inhibitory peptide of SEQ ID NO.1 is Phe-Phe-Lys-Ala (FFKA).
In another aspect, the present application provides a composition comprising the above peptide and a pharmaceutically, food or nutraceutical acceptable adjuvant.
In another aspect, the present application provides the use of the above peptide or composition for the preparation of an angiotensin converting enzyme inhibitor.
In another aspect, the present application provides the use of the above peptide or composition for the manufacture of a medicament for the treatment of hypertension.
In another aspect, the present application provides the use of the above peptide or composition in the preparation of a blood pressure lowering food or health product suitable for hypertensive population.
In another aspect, the present application provides a method of screening for the above peptide, the method comprising:
(1) enzymolysis: hydrolyzing the multicladium algae red protein solution by using an enzyme method to obtain a protein hydrolysate;
(2) screening: carrying out ultrafiltration treatment on the protein hydrolysate; obtaining a peptide fragment sequence with higher confidence in the ultrafiltration component by an ultrahigh pressure liquid chromatography-mass spectrometry method; virtually screening the obtained peptide fragment sequence, scoring according to bioinformatics prediction, and screening the polypeptide which is nontoxic, has high biological activity and has angiotensin converting enzyme inhibitory activity;
(3) in vitro activity assay: high pressure liquid chromatography is used for in vitro determination of angiotensin converting enzyme inhibitory activity of the polypeptide.
Further, the hydrolysis uses alkaline protease.
Further, the ultrafiltration fraction was a < 3kDa fraction.
Advantageous effects
The invention discloses a multiclada algae phycoerythrin angiotensin converting enzyme inhibitory peptide and a preparation method and application thereof, the application screens and obtains unreported small peptide FFKA capable of effectively inhibiting the activity of angiotensin converting enzyme from multiclada algae phycoerythrin for the first time, and defines the structure of the small peptide FFKA, and the FFKA has the advantages of safety, no toxic or side effect and high biological activity, so that the FFKA has good potential and application prospect when being used as a functional component in foods, health care products and blood pressure lowering medicines.
Drawings
FIG. 1 is a graph of the results of mass spectrometry analysis of FFKA.
Detailed Description
Hereinafter, the present invention will be described in detail. Before the description is made, it should be understood that the terms used in the present specification and the appended claims should not be construed as limited to general and dictionary meanings, but interpreted based on the meanings and concepts corresponding to technical aspects of the present invention on the basis of the principle that the inventor is allowed to define terms appropriately for the best explanation. Accordingly, the description proposed herein is just a preferable example for the purpose of illustrations only, not intended to limit the scope of the invention, so it should be understood that other equivalents and modifications could be made thereto without departing from the spirit and scope of the invention.
The following examples are given by way of illustration of embodiments of the invention and are not to be construed as limiting the invention, and it will be understood by those skilled in the art that modifications may be made without departing from the spirit and scope of the invention. Unless otherwise specified, reagents and equipment used in the following examples are commercially available products.
Example 1 extraction of phycoerythrin from Polysiphonia urceolata
(1) The multitubular algae is added according to the proportion of 1: dispersing in distilled water at a ratio (w/v) of 5-10, soaking for 6-12 hr, freezing, thawing in running water or 37 deg.C water bath, and repeating for 3 times. Centrifuging at 6000rpm for 15min, and collecting supernatant to obtain crude protein extractive solution.
(2) Ground ammonium sulfate powder was added to the crude protein extract to make the saturation degree 60%. Stirring while adding until the ammonium sulfate powder is completely dissolved, and then continuously stirring for 1-2 hours. Then placing the mixture in a refrigerating chamber of a refrigerator, and standing for 6-12 hours. 10000-12000rpm for 15min, and taking the precipitate. The precipitate was reconstituted with a suitable amount of 20mM acetate buffer (pH5.8, containing 50mM NaCl), centrifuged, the precipitate discarded, and the resuspension was dialyzed against a dialysis bag, with the acetate buffer (20mM, pH5.8, containing 50mM NaCl) being replaced frequently during dialysis. Collecting dialysate, centrifuging, and collecting supernatant. The supernatant is the crude extract of phycoerythrin from Polysiphonia urceolata.
(3) The crude extract of phycoerythrin was extracted in a suitable amount and added to DEAE Sepharose Fast Flow column equilibrated with acetic acid buffer (20mM, pH5.8, containing 50mM NaCl) to purify phycoerythrin by anion exchange chromatography. The column was washed with acetic acid buffer (20mM, pH5.8, containing 50mM NaCl) to remove impurities and excess sample, and then eluted with 20mM acetic acid buffer (pH 4.0, containing 50mM NaCl) to collect the eluted red liquid (i.e., Dunaliella red protein). Dialyzing with dialysis bag, and replacing ultrapure water for 3 times during dialysis. Centrifuging the dialyzate, and taking supernatant to obtain purified phycoerythrin solution.
Example 2 preparation of Polysiphonia urceolata phycoerythrin peptide
(1) Adjusting the pH value of the multicladus algae hemoglobin solution to 10.5, then adding 3000U/g of alkaline protease, mixing uniformly, placing in a shaking table for oscillating enzymolysis, wherein the rotation speed of the shaking table is 100-.
(2) And (4) after enzymolysis, boiling the enzymolysis liquid in a water bath for 10min to inactivate residual enzyme.
(3) Centrifuging at 10000-12000rpm at 4 ℃ for 15min, collecting supernatant, and discarding precipitate. The supernatant is the multicladium algae phycoerythrin peptide solution.
(4) And (3) centrifuging at 6000rpm for 30min by using an ultrafiltration centrifugal tube with the molecular weight cutoff of 3kDa, and sucking the solution cutoff in the ultrafiltration tube, namely the ultrafiltration component with the molecular weight less than 3 kDa.
(5) Collecting ultrafiltration components with molecular weight less than 3kDa, and freeze-drying under vacuum to obtain multicladium algae phycoerythrin peptide lyophilized powder.
Example 3 Structure identification of Polysiphonia urceolata phycoerythrin peptide
(1) Dissolving multiclada phycoerythrin peptide freeze-dried powder with the molecular weight less than 3kDa in ultrapure water, filtering by using a 0.22um water system needle filter to remove particles, and then performing mass spectrum identification on the phycoerythrin peptide by using an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-TOF-MS/MS) method. The UPLC has a mobile phase A of water solution (containing 0.1% formic acid), a mobile phase B of acetonitrile solution (containing 0.1% formic acid), an elution time of 60min, gradient elution conditions shown in Table 1, a sample amount of 5 μ L, and a flow rate of 300 μ L/min.
TABLE 1 ultra high performance liquid chromatography elution conditions
Tandem mass spectrometry was performed in positive ion mode, secondary mass spectrometry, and 100-2000m/z full MS scan at 120000 resolution, with the specific mass spectrometry parameters set as shown in Table 2.
TABLE 2 tandem Mass Spectrometry conditions
(2) Mass spectrometry data analysis
Converting an original File obtained by UPLC-MS/MS analysis into a mass spectrum universal File in an MGF format by using MM File Conversion software, retrieving protein data in an uniport database (http:// www.uniprot.org/taxonomy/8139) by using a Mascot mass spectrum data online analysis platform (http:// www.matrixscience.com /), and analyzing mass spectrum information in the MGF File, wherein the specific retrieval parameters are as follows: fixed Modifications (Carbamidomethyl, C), Variable Modifications (Oxidation, M), enzyme (none), Maximum modified Cleages (1), Peptide Mass Clearance (1.2Da), Fragment Mass Clearance (0.6Da), Mass valves (MonoSotopic), Peptide charge (1+,2+ and 3+), Signal threshold (0.05).
(3) The amino acid sequence of the phycoerythrin peptide is Phe-Phe-Lys-Ala (FFKA) identified by UPLC-ESI-TOF-MS/MS. The results of mass spectrometry are shown in FIG. 1. The results of molecular weight and hydrophobicity are shown in Table 3.
Example 4 bioinformatics prediction of multiclada phycoerythrin peptide FFKA
(1) Prediction of potential biological activity of peptides
The potential biological activity of the obtained polypeptide sequence was analyzed using the PeptideRanker online platform (http:// distilldeep. ucd). Ranking according to the biological activity prediction probability of the polypeptide, wherein the preset threshold value of the PeptideRanker prediction model is 0.5, and the polypeptide is considered to have biological activity if the threshold value is more than 0.5. The predicted value of the new peptide FFKA selected by the application is 0.91 (see Table 3 for details). The result of predictive analysis of bioinformatics shows that the potential biological activity of FFKA is high.
TABLE 3 Mass Spectrometry and biological Activity prediction results for FFKA
(2) Prediction of potential toxicity of peptides
Using ToxinPrep (https://webs.iiitd.edu.in/raghava/toxinpred/multi_ submitPhp) platform, based on SVM (Swiss-Port) algorithm, to predict potential toxicity of new peptides.
According to potential toxicity analysis, the FFKA is a nontoxic peptide.
(3) Peptide FFKA and ACE molecule docking test
And carrying out an ACE molecular docking test on the screened peptide FFKA with no toxicity and high potential bioactivity. Using pepsite 2.0(http:// pepsite2. russellab. org /), AutoDock 1.5.6 and the accession number PDB ID from the PDB database: 1O8A and calculating docking score, using Swiss-PdbViewer 4.1.0 to look at the binding sites of the molecular docks and polypeptides with ACE. Peptide docking affinity to ACE (p < 0.05) and potential binding sites were calculated by pepsite 2.0 for ACE inhibitory peptides.
ACE interaction with its ligands involves mainly three active pockets: the S1 pocket contains Ala354, Glu384, and Tyr523 residues; the S2 pocket contains Gln281, His353, Lys511, His513 and Tyr520 residues; the S1' pocket includes only Glu162 residues. In addition, other amino acid residues, such as Glu411, Glu162, His383, and His387, also play an important role in ACE activity.
Performing molecular docking analysis on the identified peptide FFKA and ACE (PDBID: 1O8A), taking the binding degree of the peptide FFKA and an ACE active site as a mark for predicting the ACE inhibitory activity of the polypeptide, and selecting the peptide with obvious p-value difference and more amino acid residues bound with the ACE active site as a molecular docking result.
The results of the molecular docking analysis of the peptide FFKA and ACE are detailed in Table 4. The number of active sites interfacing FFKA with ACE molecules is 13.
TABLE 4 results of docking analysis of potential ACE inhibitory peptides with ACE molecules
In conclusion, the prediction result of bioinformatics shows that FFKA is a novel ACE inhibitory peptide which is safe, non-toxic, high in biological activity and has ACE inhibitory activity.
Example 5 chemical Synthesis of Polysiphonia urceolata phycoerythrin peptide FFKA and in vitro determination of ACE inhibitory Activity thereof
(1) Utilizes Fmoc amino acid solid phase synthesis technology to artificially and chemically synthesize the polypeptide FFKA. The peptide was synthesized by Nanjing peptide cereal Biotechnology GmbH. The purity of the synthetic peptide was > 95%.
(2) High Performance Liquid Chromatography (HPLC) method for determining in-vitro ACE inhibitory activity of polypeptide
The drugs and instruments used in this example are commercially available without specific reference.
Principle of determination of ACE inhibitory activity by HPLC method: ACE hydrolyzes the substrate hippuryl-histidyl-leucine (Hip-His-Leu, HHL, Sigma) to hippuric acid. When ACE inhibitors are added, the production of hippuric acid is correspondingly reduced. The inhibition rate of the inhibitor on ACE can be determined by detecting the absorption peak area of hippuric acid at the wavelength of 228 nm.
Reagent: 0.2U/mL of ACE solution (0.1M boric acid buffer, pH 8.3, containing 0.4M NaCl), 12.5mM HHL (0.1M boric acid buffer, pH 8.3, containing 0.4M NaCl), FFKA solution.
The method comprises the following steps: mu.L of peptide solution and 20. mu.L of ACE solution were taken, mixed well, bathed in water at 37 ℃ for 5min, added with 10. mu.L of HHL and 33. mu.L of 0.1M boric acid buffer (pH 8.3, containing 0.4M NaCl), mixed well, bathed in water at 37 ℃ for 60min, and then added with 100. mu.L of 1M HCl to terminate the reaction. Centrifuge at 13000rpm for 15 min. The supernatant was filtered through a 0.22 μm syringe filter, and the peak area of the product hippuric acid was determined by HPLC. The HPLC analytical parameters were: c18 column: athena C18-WP
Column temperature: 30 ℃, sample introduction: 10uL, mobile phase water: acetonitrile 1:1(v/v, 0.1% trifluoroacetic acid), flow rate: 0.4mL/min, detection wavelength: 228 nm.
The formula for calculating the ACE inhibition rate is as follows:
I(％)＝(A control -A inhibition )/A control ×100
in the formula A control Peak area of hippuric acid without addition of inhibitory peptide, A inhibition The peak area of hippuric acid generated by peptide is added.
Adjusting final concentration of polypeptide in ACE enzyme activity reaction system to 0.5, 1, 2, 4, 10mM, determining FFKA inhibition rate according to the above experiment method, setting 3 parallels for each concentration, and calculating peptide IC 50 Value, i.e. the concentration of peptide that is able to inhibit 50% of ACE activity. The results are shown in Table 4.
TABLE 4 ACE inhibition of FFKA polypeptides at different concentrations
Substituting the formula to calculate the IC of the ACE inhibitory peptide FFKA of the multicladium 50 The value was 2.31 mM.
In vitro test results show that the multicladium ACE inhibitory peptide FFKA has good ACE inhibitory activity, and can be used for researching and developing medicines, functional foods, health care products and the like for treating hypertension.
The above examples are only intended to illustrate the technical solution of the present invention, and not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described in the foregoing embodiments, or equivalents may be substituted for some of the features thereof; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions.
Claims (10)
1. A multicladium alga phycoerythrin angiotensin converting enzyme inhibitory peptide is characterized in that the amino acid sequence of the peptide is shown in SEQ ID NO. 1;
the amino acid sequence of the peptide is Phe-Phe-Lys-Ala (FFKA).
2. A multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide composition, characterized in that the composition comprises the multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide of claim 1 and auxiliary materials acceptable in food, drugs or health products.
3. Use of the multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide of claim 1 or the multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide composition of claim 2 in the preparation of a product having the effect of treating hypertension.
4. Use according to claim 3, wherein the product comprises a food, pharmaceutical or nutraceutical product.
5. A preparation method of multicladium algae phycoerythrin angiotensin converting enzyme inhibitory peptide is characterized by comprising the following steps:
(1) extracting phycoerythrin from multiclada: extracting phycoerythrin from the multiclada to obtain multiclada phycoerythrin solution;
(2) enzymolysis: hydrolyzing the multiclada algae phycoerythrin solution obtained in the step (1) by using an enzyme method to obtain a multiclada algae phycoerythrin peptide solution;
(3) and (3) ultrafiltration: carrying out ultrafiltration treatment on the multiclada phycoerythrin peptide solution obtained in the step (2) to obtain an ultrafiltration component;
(4) screening: and (4) screening the ultrafiltration component obtained in the step (3) to obtain the multicladium algae phycoerythrin angiotensin-converting enzyme inhibitory peptide.
6. The method for preparing multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide according to claim 5, wherein the step (1) of extracting multiclada alga phycoerythrin specifically comprises the steps of:
dispersing Polysiphonia urceolata in distilled water, soaking, freezing, thawing, repeating for multiple times, centrifuging, and collecting supernatant to obtain crude protein extractive solution;
adding ammonium sulfate powder into the crude protein extractive solution, standing, centrifuging, collecting precipitate, redissolving the precipitate, dialyzing, centrifuging dialysate, and collecting supernatant to obtain crude protein extractive solution of Polysiphonia algae;
taking a proper amount of the crude multiclada phycoerythrin extract, and purifying phycoerythrin by an anion exchange chromatography to obtain a purified phycoerythrin solution.
7. The method for preparing multicladium algae phycoerythrin angiotensin converting enzyme inhibitory peptide according to claim 5, wherein the enzymatic hydrolysis in step (3) comprises the following steps:
adjusting the pH value of the multiclada phycoerythrin solution to 10.5, then adding alkaline protease, mixing uniformly, and then placing in a shaking table for oscillating enzymolysis;
after enzymolysis, carrying out boiling water bath on the enzymolysis liquid to inactivate residual enzyme;
centrifuging, collecting supernatant, and removing precipitate to obtain supernatant as multicladus algae phycoerythrin peptide solution.
8. The method for preparing the multicladus phycoerythrin angiotensin converting enzyme inhibitory peptide according to claim 5, wherein the ultrafiltration in the step (3) is specifically: and (3) using an ultrafiltration centrifugal tube with the molecular weight cutoff of 3kDa, centrifuging, and sucking the solution cutoff in the ultrafiltration tube, namely the ultrafiltration component with the molecular weight less than 3 kDa.
9. The method for preparing multicladium alga phycoerythrin angiotensin converting enzyme inhibitory peptide according to claim 5, wherein said screening in step (4) comprises the steps of:
obtaining a peptide segment sequence with high confidence in the ultrafiltration component by ultra-high performance liquid chromatography-tandem mass spectrometry;
and virtually screening the obtained peptide fragment sequence, and screening the polypeptide which has no toxicity, high biological activity and angiotensin-converting enzyme inhibitory activity according to bioinformatics prediction scoring, namely the multicladium algae phycoerythrin angiotensin-converting enzyme inhibitory peptide.
10. The method for preparing multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide according to claim 5, wherein the in vitro activity of said multiclada alga phycoerythrin angiotensin converting enzyme inhibitory peptide is determined by: high performance liquid chromatography is used for in vitro determination of angiotensin converting enzyme inhibitory activity of the polypeptide.
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