Peptide lana1, extracted from bacterium bacillus licheniformis vk21, having antimicrobial effect

FIELD: medicine.

SUBSTANCE: biologically active peptide is proposed with the common formula: , where OBu - residue of 2-oxobutyric acid, Abu - residue of 2-aminobutyric acid, Dha - residue of 2,3-didehydroalanine, Dhb - residue of 2,3-didehydroaminobutyric acid, besides residues are in sequence linked with amide links, residues Abu3-Ala7, Abu22-Ala27 and Abu24-Ala31 are also linked pairwise with thioether links with formation of three residues of 3-methyllanthionine, residues Ala11-Ala21 are linked with thioether link to form residue of lanthionine. This peptide has antimicrobial effect at gram-positive bacteria Bacillus subtilis, strains L1 and 1621; Bacillus pumilus, strain 2001; Bacillus globigii, strain I; Bacillus amyloliquefaciens, strain I; Bacillus megaterium, strain VKM41; Mycobacterium smegmatis, strain 1171; Mycobacterium phlei, strain 1291; Micrococcus luteus, strain B 1314; Staphylococcus aureus, strain 209p; Rhodococcus sp., strain SSI.

EFFECT: increased efficiency of peptide antimicrobial action.

4 dwg, 1 tbl, 6 ex

 

The invention relates to the field of biochemistry, namely to biologically active peptides having antimicrobial activity, which may find application in medicine, veterinary medicine and food industry.

One of the topical problems of modern medicine is the development of drugs to combat infectious diseases, resistant to existing antibiotics. In food biotechnology the development of new preservatives that inhibit the growth of microorganisms that can increase the shelf life of products, reduces the cost of the process and increases productivity by reducing the time and the temperature of heat treatment.

Over the last three decades of the twentieth century, the Arsenal of available antibiotics was only enriched by new representatives are already known classes of these substances. In 2000-ies after a long break in the market began to appear the first antibiotics with a completely new structure: oxazolidine (linezolid), cyclic lipopetides (daptomycin), glycylcyclines (tigecycline) [J.H. Song What's new on the antimicrobial horizon? // Int. J. Antimicrob. Agents. - 2008. - 32(4). - S207-13].

One of the promising classes of compounds to create antibiotics that are active against drug-resistant microorganisms, are antimicrobial peptides [Bommarius Century, Klman D. Antimicrobial and host defense peptides for therapeutic use against multidrug-resistant pathogens: a new hope on the horizon // IDrugs. - 2009. - 12(6). - 376-80]. Antimicrobial peptides prokaryotic origin are called bacteriocins. Based on the most common structural characteristics of bacteriocins of gram-positive bacteria are divided into four classes: (I) antibiotiki (lowlands, epidermin); (II) a thermostable peptides with molecular weight less than 10 kDa (Sabatini, plantaricin); (III) thermolabile proteins with a molecular mass of less than 30 kDa, close to the colicins (geneticin, millerites); IV) complex bacteriocins, including carbohydrate or lipid part [SM Asaduzzaman, Sonomoto K. Lantibiotics: diverse activities and unique modes of action. // J. Biosci. Bioeng. - 2009. - 107(5). -P.475-87]. Lantibiotic - synthesized on ribosomes and contains significant posttranslational modification of peptides, the distinguishing feature of the structure which is the presence of residues of lanthionine, metallothionine and digidrirovanny amino acids. Thioester bond created by the interaction of cysteine residues with residues 2,3-didehydrothymidine and 2,3-didehydrothymidine acids play a key role in the emergence of antibacterial properties [O. McAuliffe, Ross, R.P., Hill .Lantibiotics: structure, biosynthesis and mode of action// FEMS Environ. Rev. - 2001. - 25(3). - P.285-308].

Known lantibiotic lacticin 3147 LtnA1, isolated from the bacterium Lactococcus lactis having a molecular mA is su 3322 and possessing activity against gram-positive bacteria. Molecule lacticin 3147 LtnA1 contains 30 amino acid residues, including residues 2,3-didehydrothymidine acid and 2-aminobutyric acid. Molecular structure is stabilized by four thioester bonds [Martin NI, Sprules T, Carpenter MR, Cotter PD, Hill C, Ross RP, Vederas JC. Structural characterization of lacticin 3147, a two-peptide lantibiotic with synergistic activity. Biochemistry. - 2004. - 43(11). - P.3049-56].

Known closest to the claimed isolated from the bacterium Bacillus licheniformis ATCC 14580 peptide lichenized Bliα with a molecular mass of 3250,5 Yes, active against gram-positive bacteria [Begley, M., Cotter P.D., Hill, C., Ross R.P. Rational genome mining for LanM proteins leads to the identification of a novel two-peptide lantibiotic, lichenicidin // Appl. Environ. Environ. - 2009]. Model molecules limenitidinae Bliα was built using strategies in silico on the basis of nucleotide sequence that encodes a precursor peptide, and data structure known lantibiotics. Probable structure Bliα includes a 32 amino acid residue, including the remains of 2-aminobutyric acid, 2,3-didehydrothymidine, 2,3-didehydrothymidine acid, and four stable thioester bonds.

The invention solves the problem of expanding the range of antimicrobial peptides.

The problem is solved by peptide LanA1 having antimicrobial activity, of General formula:

where OBu - balance 2-oxomalonate to the slots, Abu - balance 2-aminobutyric acid, Dha is the residue of 2,3-didehydrothymidine, Dhb residue of 2,3-didehydrothymidine acid.

The structure of the peptide includes the N-terminal residue of 2-oxomalonate acid and 31 amino acid residue, United in the sequence of amide bonds. The composition of the amino acid sequence along with the remnants of the genetically encoded amino acids include balances of non-canonical amino acids Abu Dha and Dhb. In addition, the structure of the peptide stabilizes four thioester linkages: the remnants of the Abu3and Ala7Abu22and Ala27Abu24and Ala31connected in pairs thioester bonds with the formation of three residues 3-metallothionine (MeLan), and residues Ala11and Ala21connected by thioester bond with the formation of the remainder of lanthionine (Lan). Thus, the claimed peptide belongs to the class of lantibiotics.

The presence of these non-canonical amino acid residues and thioester linkages, as well as N-terminal residue of 2-oxomalonate acid makes it impossible to determine the primary structure of the peptide traditional methods - step degradation of the amino acid chain Admino and mass spectrometric analysis. Complete primary structure of the e can be derived only on the basis of the data on the nucleotide sequence, encoding the peptide and its predecessor, including those involving information on the structure of other members of the class of lantibiotics and currently available information about the specificity of modifying enzymes. Complete primary structure of the inventive peptide can be reliably determined by comparing the results of sequencing the nucleotide sequence that encodes a precursor peptide, and data NMR spectroscopy.

The molecular mass of peptide LanA1 is 3249,5 Yes.

The inventive peptide LanA1 has a number of significant differences from its nearest analogue - limenitidinae Bliα. Thus, in the structure of limenitidinae Bliα as N-terminal residue is alanine, and the claimed peptide contains in this position, the remainder of the 2-oxomalonate acid. In addition, limenitidinae Bliα residues Ala1and Ala7connected by thioester bond with the formation of lanthionine (Lan), and in the claimed peptide such a connection connects the remnants of the Abu3and Ala7with the formation of 3-metallothionine (MeLan). An advantage of the claimed peptide LanA1 is the possibility of its use against sensitive strains of microorganisms resistant to the peptide-analogue. An advantage of the claimed peptide LanA1 is also the possibility of its receipt from the culture fluid of producing strains of the Bacillus licheniformis VK21, and not from the cell sediment that can simplify the purification of the peptide.

Peptide LanA1 with the stated structure possesses antimicrobial activity against gram-positive bacteria Bacillus subtilis, strains L1 and 1621; Bacillus pumilus, strain 2001; Bacillus globigii, strain I; Bacillus amyloliquefaciens strain I; B. megaterium Bacillus, strain VKM41; Mycobacterium smegmatis strain 1171; Mycobacterium phlei, strain 1291; Micrococcus luteus strain W; Staphylococcus aureus, strain 209p; Rhodococcus sp., strain SS1.

Peptide LanA1 can be obtained from a natural source - thermophilic gram-positive bacterium Bacillus licheniformis VK21.

The invention is illustrated graphics.

Figure 1 shows the chromatogram of purification LanA1 on column Xterra MS C18. Figure 2 presents a fragment of two-dimensional NMR TOCSY spectrum of peptide LanA1 in methanol (27°C, pH 3.5): the vertical dashed lines indicate the spin system of individual residues of the peptide; for some signal peptide is observed the presence of two or more spin systems, which is associated with the conformational heterogeneity of the N-terminal fragment of the peptide, namely cis-trans-isomerism of the peptide bond Lys12-Pro13and the presence of multiple conformations of the portion of the molecule OBu1-Ile7; the signals for the different conformations of the peptide are connected by horizontal dotted lines, and names of corresponding residues of the molecule are underlined. Figure 3 presents a fragment of a two-dimensional Airspace NOESY peptide LanA1 in methanol (27°C, pH 3.5); frequency signals residues Lan and MeLan shown in dotted lines; AEO cross-peaks, which allows to make a conclusion about the location of the thioester linkages in the molecule peptide, a dotted ellipses. 4 shows the mass spectrum of the high-resolution peptide LanA1.

The invention is illustrated by the examples.

Example 1.

Culturing cells of a strain of Bacillus licheniformis VK21

Culture grown on LB-agar at 45°C overnight, then washed with 10 ml growth medium C2Mn (Kazarinova acid - 0,15%; KCl - 0,02%; K2HPO4to 0.3%; KH2PO4- 0,1%; MgSO4×7H2O - 0,02%; MnSO4×5H2O - 0,001%). Aliquots of cell suspension volume of 1.5 ml added to a flask with 750 ml containing 150 ml of medium C2Mn, and incubated on a rotary shaker at 45°C and the rotation speed of 200 rpm for 6 h until the culture optical density OD6201.5 (exit culture in the stationary phase of growth).

Example 2.

The selection of antimicrobial peptide LanA1 from the culture fluid of thermophilic gram-positive bacterium Bacillus licheniformis VK21

After culturing the cells of thermophilic bacteria Bacillus licheniformis VK21 separated by centrifugation at 8000 g for 50 min, the Supernatant was concentrated in 20 times on a rotary vacuum evaporator. To the resulting solution was added two volumes of acetone and remove sediment centrifuger the cation at 8000 g for 40 minutes The obtained supernatant evaporated on a rotary vacuum evaporator to dryness and pererastayut in 50 ml of water. Next, perform a single extraction with equal volumes of n-butanol, after which the aqueous phase is removed using a separating funnel, and the resulting organic extract is evaporated to dryness.

Dry extract pererastayut in 50 ml of buffer A1(30 mm ammonium acetate, pH 5,6, 30% acetonitrile and applied to a column with a carrier Silasorb C8, equilibrated with buffer A1. After washing the column with 100 ml of buffer A1contacting a carrier substances elute with 50 ml of buffer B1(30 mm ammonium acetate, pH 5,6, 80% acetonitrile) at a flow rate of 2 ml/min

The obtained eluate was diluted with 30 mm ammonium acetate, pH 5,6, reducing the concentration of acetonitrile to 30%, and applied on the column with the carrier Diasorb-130C8T. After washing the column with buffer A1prior to the zero line carry out the separation in a linear gradient of buffer B1from 0 to 100% within 95 minutes (1,05% min-1) at a flow rate of 2 ml/min Detection is carried out at a wavelength of 214 nm.

The active fraction collected in the period from 50 to 55 min, concentrated and subjected to further fractionation using reversed-phase high-performance liquid chromatography on a column Xterra MS C18counterbalanced to a buffer And2(5% acetonitrile, 60% m is tanol), in a linear gradient of buffer In2(35% acetonitrile, 60% methanol) from 0 to 100% over 40 min (2,5% min-1) at a flow rate of 0.5 ml/min Detection is carried out at a wavelength of 214 nm.

The content of peptides in fractions estimated using MALDI-TOF mass spectrometric analysis instrument Reflex III (Bruker Daltonics). As a matrix, use 0,15M 2,5-dihydroxybenzoic acid in a mixture containing 25% methanol and 0.1% triperoxonane acid. The sample is irradiated with a UV laser with a wavelength of 337 nm.

In the chromatographic separation on a column Xterra MS C18the active fractions revealed a main peak emerging from the column with acetonitrile 17% (figure 1).

Example 3.

Determination of the nucleotide sequence that encodes a precursor peptide LanA1

Genomic DNA of Bacillus licheniformis VK21 extracted from 20 ml of bacterial culture, which is obtained according to the method described in example 1. The culture fluid centrifuged at 3000 g for 5 minutes Cellular precipitate is washed with a 0.85% solution of sodium chloride, followed by re-centrifugation. Sediment resuspended 1 ml of TEN buffer [0,15M NaCl, 0.1 M Tris-HCl (pH 8.0), 0.1 M EDTA], in which is dissolved lysozyme at a concentration of 4 mg/ml of the resulting suspension is incubated for 45 min at 37°C, then add 0.25 ml of 8.5% sodium dodecyl sulfate and vyd ribaut 30 min at 75°C. To the resulting lysate add 375 ál of 5 M potassium acetate (pH 5.2), incubated the mixture for 20 min at 4°C and then centrifuged at 10,000 g for 5 minutes, the Resulting supernatant is poured, the precipitate is dissolved in 100 μl of buffer TE [10 mm Tris-HCl (pH 8.0), 1 mm EDTA]. Then hold clearing the obtained genomic DNA with a mixture of phenol-chloroform (1:1), precipitated DNA by alcohol and pererastayut in 200 μl of water.

Amplification of DNA encoding a precursor peptide LanA1, performed using primers 1-4 (SEQ ID Nos. 1-4) in two stages by the method of "nested" PCR. In the composition of the reaction mixture in both reactions containing 2 ál of 10x buffer for DNA polymerase Taq Advantage 2 (Clontech), 3 μl of a solution of equimolar mixture of dNTP (1.25 µm), 1 µl of DNA solution matrix, 0,5 µl of a solution of DNA polymerase Taq Advantage 2 (Clontech), 1 μl of solutions of two gene-specific primers (10 pmol/μl) and 12 μl of water; total volume of the mixture is 20.5 mm. In the first reaction mixture add primers 1 (SEQ ID No. 1) and 2 (SEQ ID No. 2) and a solution of genomic DNA Century licheniformis as a DNA template. The second reaction mixture add primers 3 (SEQ ID No. 3) and 4 (SEQ ID No. 4) and the products of the first reaction at a dilution of 1:20 as DNA template. Temperature of both reactions: 94°C - 2 min (hot start); then 30 cycles of: 94°C 30 s, 52°C for 40 s, 72°C - 60 C. the PCR Products separated on an agarose gel and visualize using bromide those who Oia. The product of the second reaction size 698 gel elute from agarose and is sequenced.

DNA sequencing is performed using an assay kit ABI PRISM BigDye Terminator v.3.1 with subsequent analysis of the reaction products on an automated DNA sequencing machine (ABI PRISM 3100-Avant (Applied Biosystem). The result is the nucleotide sequence of SEQ ID No. 5, part of which encodes amino acid sequence SEQ ID No. 6 predecessor antimicrobial peptide LanA1.

Example 4.

The primary structure of the selected peptide LanA1

To define the structure of the selected antibiotic used method of NMR spectroscopy. Peptide antibiotic LanA1 dissolved in methanol (2.0 mg/450 ál, pH 3.5). The NMR spectra of peptide receive at a temperature of 27°C on a spectrometer Bruker Avance-700 (Germany) with an operating frequency of 700 MHz. For the measurement of NMR spectra using the sensor triple resonance (1H,13C,15N) with cryogenic cooled1N coil (Bruker, Germany).

Based on the analysis of two-dimensional1H-NMR TOCSY spectra (figure 2) and NOESY (figure 3) using standard procedures [Wuthrich K. NMR of Proteins and Nucleic Acids. // New York: John Wiley Sons, 1986] provide a full assignment of the signals of nuclei1H sample. Based on the analysis of two-dimensional13C-NMR HSQC spectrum spend a full assignment of the signals13With nuclei, atoms which are covalently bound to prisoedinyaemoy.

Compare the results of the classification with the results of sequencing the nucleotide sequence of the gene antimicrobial peptide LanA1 from strain VK21 thermophilic bacteria Bacillus lichenifbrmis allows us to conclude that the peptide antibiotic LanA1 has the following primary structure:

which is obtained by post-translational modification propeptide having the sequence SEQ ID No. 6.

The presence of N-terminal groups OBu1confirm, using two-dimensional NMR TOCSY spectra and13C-HSQC, by observing the characteristic signals from the fragment CH3-CH2-(1N 2,93 and 1.09 MD;13With 30.1 and 5.8 MD).

Location thioester linkages in the molecule peptide LanA1 is determined on the basis of the analysis of two-dimensional NMR NOESY spectrum (figure 3), watching AEO cross-peaks between the aliphatic protons in residues Lan or MeLan. The presence of AAA cross-peaks allows us to conclude that the peptide LanA1 thioester links connect pairs of residues Ala11and Ala21Abu3and Ala7Abu22and Ala27Abu24and Ala31with the formation of a residue Lan and three residues MeLan.

Example 5.

Determination of the molecular mass of the peptide by the method of mass spectrometry

Mass spectra get on a hybrid mass spectrometer LTQ FT (Thermo Electron, Germany), which consists of a linear quadrupole ion the trap and the mass spectrometer ion cyclotron resonance Fourier transform (DDI PF). As an ion source using a universal source of ionization Finnigan Ion Max Source (Thermo Electron, Germany) in mode elektrorazpredelenie. For peptide LanA1 see set dasarani and treasurary ions corresponding to the monoisotopic molecular mass of the peptide 3249,51±0,01 Yes (figure 4). The resulting mass with regard to the accuracy of measurement coincides with the calculated monoisotopic molecular mass of the peptide LanA1 (3249,515 Yes). The measured mass of the peptide LanA1 is consistent with the calculated mass of propeptide (3374,605 Yes) subject to 7 sites dehydration (-126,074 Yes) and one of the deamination reaction with the addition of a water molecule (+0,984 Yes). Mass spectrometric analysis confirms the claimed structure of the peptide LanA1.

Example 6.

Determination of antimicrobial activity of selected peptide LanA1 Antimicrobial activity of the selected peptide determined by radial diffusion of the peptide in agarose gel with gram-positive bacteria:

Bacillus subtilis strains L1 and 1621; Bacillus pumilus, strain 2001; Bacillus globigii, strain I; Bacillus amyloliquefaciens strain I; B. megaterium Bacillus, strain VKM41; Mycobacterium smegmatis strain 1171; Mycobacterium phlei, strain 1291; Micrococcus luteus strain W; Staphylococcus aureus, strain 209p; Rhodococcus sp., strain SS1. The test culture grown over night in a dense environment. Grown colonies are transferred into 3 ml of liquid medium and incubated on a rotary shaker until the culture optical density OD6201,2 Aliquot cell suspension is added to 12 ml of molten and cooled depleted medium (9 mm phosphate buffer, pH 6.5; 0,03% TSB, 1% agarose), and the mixture is poured cups with a diameter of 90 mm Final concentration of bacteria is 2·105CFU/ml In the layer of agarose drill holes with a diameter of 2 mm and contribute 5 µl of the sample solution in 20% methanol. As a control using 20% methanol. Cup incubated, without turning for 3 h, after which the first layer of the agarose layer 12 ml of enriched environment (2LB, 1% agarose). Antimicrobial activity of the peptide is fixed after 20 h in the presence of zones of inhibition of growth of test cultures (see table).

Antimicrobial activity of the peptide LanA1
The test microorganismActivity
Bacillus subtilis strain L1+
Bacillus subtilis strain 1621+
Bacillus pumilus, strain 2001+
Bacillus globigii, strain I+
Bacillus amyloliquefaciens strain I+
B. megaterium Bacillus, strain VKM41++
Mycobacterium smegmatis strain 1171+
Mycbacterium phlei, strain 1291+
Micrococcus luteus strain W+++
Staphylococcus aureus, strain R+
Rhodococcus sp., strain SS1+
(+) - diameter of zone of inhibition of growth of less than 0.5 cm;
(++) - the diameter of zone of inhibition of growth of 0.5 to 1 cm;
(+++) - diameter of zone of inhibition of growth of more than 1 cm

It is shown that the selected peptide LanA1 in the amount of 4 μg/well exhibits antimicrobial activity and inhibits the growth of all tested gram-positive bacteria. The most sensitive to the selected peptide crops are .luteus and .megaterium. The least pronounced inhibitory effect of the selected peptide in relation .globigii, .smegmatis, .phlei and Rhodococcus sp.

The peptide having antimicrobial activity, of General formula:

where JVI - balance 2-oxomalonate acid, Abu - balance 2-aminobutyric acid, Dha is the residue of 2,3-didehydrothymidine, Dhb residue of 2,3-didehydrothymidine acid, and residues in the sequence are connected by amide bonds, the remnants of the Abu3-Ala7Abu22-Ala27and Abu24-Ala3111-Ala21connected by thioester bond with the formation of the remainder of lanthionine.



 

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3 dwg, 5 ex

FIELD: biotechnologies.

SUBSTANCE: in modified molecule IL-4RA, which inhibits mediated IL-4 and IL-13 activity, amino-acid remains 37, 38 or 104 represent cysteine. Polynucleotide, which codes specified antagonist, in composition of expression vector, is used to transform host cell and produce IL-4RA. Produced molecule IL-4RA is PEGylated and used to eliminate abnormalities that are related to high activity of IL-4 and IL-13.

EFFECT: invention makes it possible to produce antagonist with longer period of half-decay compared to non-modified IL-4RA.

17 cl, 1 dwg, 7 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: in dissolvent, which contains from 55% to 70% of water (wt/wt), precursor of insulin or precursor of insulin derivative is exposed to fermentative splitting at alkaline values of pH. In process of fermentative splitting, they use tripsin or lysil-specific protease, preferably Achromobacter lyticus protease I. Then without separation of intermediate product from reaction mixture, mentioned intermediate product is fermentatively complemented with nucleophilic compound, which represents aminoacid ether, aminoacid amide, peptide, peptide ether or peptide amide in reaction mixture, having water content in the range from 10% to 50% of water (wt/wt), at acidic values of pH, close to neutral pH value. If required, protective group (s) is/are removed.

EFFECT: preparation of insulin compound from its precursor by efficient improved method.

24 cl, 5 ex

FIELD: medicine.

SUBSTANCE: invention is related to nucleic acids and multidomain proteins, which are able to bind vessel endotheliocyte growth factor (VEGF), and may be used in medicine. Recombinant method is used to produce polypeptide, which consists of component (R1R2)X and, unnecessarily, multidomain component (MC), which represents aminoacid sequence with length from 1 to 200 of amino acids, having at least one remainder of cysteine, where X≥1, R1 means antibody-like (Ig) domain 2 of VEGF receptor Llt-1, and R2 means Ig-domain 3 of VEGF receptor Flk-1. Produced fused polypeptide does not contain multidomain component in case, when X=2, and in case when X=1, multidomain component represents aminoacid sequence with length from 1 to 15 amino acids. Produced polypeptide is used in composition of pharmaceutical compound for VEGF-mediated disease or condition.

EFFECT: invention makes it possible to produce highly efficient trap of VEGF, special structure of which is suitable for local introduction into specific organs, tissues or cells.

16 cl, 3 tbl, 7 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology, specifically to a method of producing recombinant protein human albumin-interleukin-2 or recombinant protein human albumin-alpha 16-interferon, modified by attachment of human albumin. The method involves technology of culturing yeast strain Pichia pastoris PS106/pPIC9HAbIL-2 or yeast strain Pichia pastoris PS106/pPIC9HAbIFNa-16 in modified culture medium BMGY, after which induction synthesis of target proteins is carried out at low temperature. Further, cells are removed and the medium is concentrated. Target proteins are then precipitated using ammonium sulphate or polyethyleneglycol 3350. Target proteins are then separated by gel filtration on Sephacryl HR 200 or BioRad P-300 sorbents. Finally, affinity chromatography is then done on Cibacron F3GA sorbent.

EFFECT: invention simplifies and increases efficiency of the technology of purifying target proteins, and also allows for obtaining biologically active hybrid proteins, suitable for making medicinal agents.

3 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: described is a peptide having antimicrobic action, which has general formula: , where OBu is a 2-oxobutyric acid residue, Abu is a 2-aminobutyric acid residue, Dha is a 2,3-didehydroanaline residue, Dhb is a 2,3-didehydroaminobutyric acid residue, where residues in the sequence are joined by amide bonds, residues Ala7 and Ala11, Ala19 and Ala23 are joined in pairs by thioester bonds to form two lanthionine (Lan) residues, Abu25 and Ala28, Abu29 and Ala32 are joined in pairs by thioester bonds to form two 3-methyllanthionine (MeLan) residues.

EFFECT: high antimicrobic action of the peptide.

4 dwg, 1 tbl, 6 ex

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