What Is an Antimicrobial Peptide?

Antimicrobial peptide

Antibacterial peptides refer to a class of basic polypeptide substances with antibacterial activity that are induced by insects. They have a molecular weight of about 2000 to 7000 and consist of 20 to 60 amino acid residues. Most of these active peptides have strong alkaline, thermal stability, and broad-spectrum antibacterial properties. The first antimicrobial peptide to be discovered in the world was a peptide produced by Swedish scientist G. Boman and others in 1980, which was induced by S. guberii silkworm pupae with injection of N. spp. And E. coli. It was named Cecropins.

Initially, when studying the immune mechanism of the North American silkworm, it was discovered that after the diapause pupae were induced by external stimuli, peptides with bacteriostatic effects were produced in their hemolymphs. Such antibacterial peptides were named Cecropins. Later, antibacterial peptides with similar structures were also isolated from other insects, amphibians, and mammals, and the structures of more than 70 antibacterial peptides were determined. In the years after 1980, peptides with antibacterial activity were discovered and isolated from bacteria, fungi, amphibians, insects, higher plants, mammals, and even humans. Because such active peptides have a broad spectrum of high-efficiency bactericidal activity against bacteria, they are named "antibacterial pepitides, ABP", translated into Chinese as antibacterial peptides, and their original meaning is antibacterial peptides. With the further development of people's research work, it has been discovered that certain antibacterial peptides have a powerful killing effect on some fungi, protozoa, viruses and cancer cells. Therefore, many scholars have named these active peptides. " "peptide antibiotics"-peptide antibiotics.

In November 2013, Zhang Yun's group at the Kunming Institute of Zoology, Chinese Academy of Sciences, found that natural antibacterial peptides have selective immune activation and regulatory functions, and have good preventive and protective effects on sepsis. ^[1]

Chinese name: Antibacterial peptides
English name: antimicrobial peptide
nickname: Human defense peptides (HDPs)
Molecular weight: <10KDa

Water soluble: Water soluble fat
Exterior: -helix or -sheet
Application: The aquaculture industry is mainly used to replace antibiotics for health care; it can be used to treat immunodeficiency diseases
main effect: Antibacterial; immune regulation; repairing damage

Antimicrobial peptide classification

Antibacterial peptide structure classification

Antibacterial peptides can be divided into many types according to their structure, of which Cathelicidin and Defensin are

Main types; they can be divided into 5 categories: (1) single-chain cysteine-free -helixes, or peptides consisting of two coils of random coils connected by random coils; (2) rich in Antibacterial peptides with certain amino acid residues but no cysteine residues; (3) antibacterial peptides containing one disulfide bond; (4) having two or more disulfide bonds and having a -sheet structure (5) Peptides with antibacterial activity derived from other larger peptides with known functions. The earliest isolated Cecropins and Magainins isolated from Xenopus belong to the first class of antibacterial peptides, which are often also called Cecropin antibacterial peptides. The current research on such antibacterial peptides is also in-depth.

Classification of antimicrobial peptide sources

It can be divided into 6 categories:

(1) Insect antibacterial peptides Insects are the largest biological species in the population, and the amount of antibacterial peptides is difficult to estimate. At present, more than 200 kinds of insect antibacterial peptides have been found in 8 insects such as Lepidoptera, Diptera, Coleoptera, and Odonata, and only 40 antibacterial peptide genes have been obtained from the silkworm, the insect.

(2) Mammalian Antimicrobial Peptide Cecropin P1 was isolated from the pig small intestine for the first time in 1989. At present, at least 18 species have been isolated from pigs, at least 30 species from sheep, and at least 30 antimicrobial peptides from cattle. The defensins found in the human body belong to a large family of antibacterial peptides, and are divided into three major categories based on the differences in the spatial structure of the amino acid and the secretion site: human -defensin, human -defensin (human -defensin (HD)) and human -defensin [5], it has been found that there are more than 35 human defensins, including 10 very important defensins.

(3) Amphibian antibacterial peptides Amphibians have multiple functions. Numerous skin-active peptides present in skin secretions have diverse biological activities, most of which have certain antimicrobial activity. It is a very ancient and effective natural defense substance in evolution, which is often classified as an antibacterial peptide. There are more than a dozen antibacterial peptides in Xenopus laevis, which are not only expressed in the skin granular glands, but also in the gastric mucosa and small intestinal cells. The small-molecule antibacterial peptide found in Xenopus skin, magainins, is an earlier antibacterial peptide of amphibians and has high antibacterial activity. Since then, a variety of frog antibacterial peptides have been found. According to incomplete statistics, hundreds of antibacterial peptides have been extracted from the skins of about 40 species of amphibians in 8 genera of tailless amphibians, and 548 of them are included in the APD database. A large number of studies have found that frog antibacterial peptides have synergistic effects, but different frog antibacterial peptides rarely have homology.

(4) Antimicrobial peptides derived from fish, mollusks and crustaceans. In 1986, an antimicrobial peptide containing 35 amino acid residues, Pardaxin, was isolated from leopard pupa. A peptide with transmembrane action. The peptide is an ionic neurotoxin. A series of peptides with stronger antibacterial activity and lower hemolytic activity than melittin are derived from the peptide. In 1998, it was reported that parasilurus asotus secreted a 19-amino acid residue histone H2A antibacterial peptide parasin when the epithelial mucosa cell layer was injured. Its antibacterial activity was 12% of that of bombesin mainin 2. ~ 100 times. At present, more than 49 antibacterial peptides have been isolated from fish. Defensins are important antimicrobial peptides of marine molluscs such as mussels. The mussel defensins discovered so far are classified into Defensin, mytilin and myticin according to their primary structure, properties and shared cysteine sequences. Shrimp infected with bacteria can induce a variety of gene expression, including a variety of antibacterial peptide genes. Since the complete amino acid sequence of crustacean antimicrobial peptides was first reported in 1997, a variety of antimicrobial peptides have been isolated from crustaceans such as shrimp blood cells.

(5) Plant antibacterial peptides There are also some plant antibacterial peptides which are similar in structure to insect and mammal defensins in plants, and are called phytoalexins. Most plant antimicrobial peptides have good activity against plant pathogens, and some plant antimicrobial peptides are toxic to Gram-positive bacteria, negative bacteria, fungi, yeast, and mammalian cells. Thi-onins are the first antimicrobial peptides isolated from plants.

(6) Bacterial antibacterial peptides Bacterial antibacterial peptides, also known as bacteriocin, include cationic peptides and neutral peptides. Both Gram-positive and Gram-negative bacteria can be secreted. There are four types of antibacterial peptides found in bacteria: Bacitracin, Gramicidin S, Polymyxin E and Nisin. At present, there are 119 bacteriocins included in the APD database. Nisin is a short peptide containing 3 to 4 amino acid residues produced by Lactococcus. It is an acid-resistant substance, even in the stomach. It is also highly stable in low pH environments and can inhibit Gram-positive bacteria such as Clostridium and Listeria. The bacitracin mersacidin produced by Bacillus spp. Has a good inhibitory effect on "super-resistant bacteria"-methicillin-resistant Staphylococcus (MRSA). It can clear the blood, lung, liver and kidney of MRSA-infected mice by intraperitoneal administration And spleen, and did not cause significant damage to the mouse organs.

Antibacterial peptide function

Antibacterial peptides have broad-spectrum antibacterial activity, which can quickly detect and kill targets, and many of them are pure natural peptides, which makes it a potential therapeutic drug. , Fungi, parasites, tumor cells, etc. ^[2] .

Antibacterial peptides similar products

Among similar products in the industry, the number of peptide antibacterial peptides ^[3] technology is relatively mature. Is the benchmark for the veterinary medicine industry!

Antibacterial peptide effect

Antibacterial peptides have broad-spectrum antibacterial activity and have a strong killing effect on bacteria, especially their killing effect on certain drug-resistant pathogens.

In addition, people have also discovered that certain antibacterial peptides have a killing effect on some viruses, fungi, protozoa and cancer cells, and can even improve immunity and accelerate the wound healing process.

The extensive biological activity of antibacterial peptides shows its good application prospects in medicine.

Antibacterial peptide mechanism of action

Since the discovery of antimicrobial peptides, a great deal of research has been conducted on the mechanism of action of antimicrobial peptides. It is currently known that antibacterial peptides work by acting on bacterial cell membranes. Based on this, a number of models of antibacterial peptides interacting with cell membranes have been proposed. But strictly speaking, the mechanism by which antibacterial peptides kill bacteria has not yet been fully understood.

At present, it is generally believed that Cecropin antibacterial peptides act on cell membranes, forming transmembrane ion channels on the membrane, destroying the integrity of the membrane, causing leakage of cell contents, thereby killing the cells.

The idea that antibacterial peptides destroy the integrity of the membrane and cause the loss of the internal and external barriers of cells to kill bacteria has been basically unified, but its specific action process, whether there are specific membrane receptors, and whether other factors cooperate Other issues are not very clear, and there are different views. The mechanism of action of different antimicrobial peptides may be different and needs further study

Antibacterial peptide genetic engineering

Antibacterial peptides are found in very small amounts in animals. Extraction of antibacterial peptides from animals has low yield, time-consuming, complicated technology, and high cost, and it is impossible to achieve large-scale production, which has become the biggest obstacle that restricts antibacterial peptides from entering practical applications. Therefore, it is of great significance to carry out research on genetic engineering of antibacterial peptides.

At present, most of the genetically engineered drugs that have entered clinical applications are produced using prokaryotic expression systems. However, due to the killing effect of antibacterial peptides on bacteria, it is not possible to directly express biologically active antibacterial peptides with prokaryotic expression systems. Expression will bring great trouble to the post-processing of expression products. Therefore, researchers at home and abroad mostly use eukaryotic expression systems for genetic engineering research of antibacterial peptides.

In recent years, research on yeast as a genetically engineered recipient has attracted much attention. Yeast has a more complete gene expression regulation mechanism than Escherichia coli and the ability to process and modify expression products. It does not produce endotoxin. It is a gene Good eukaryotic gene recipient bacteria in engineering. Since Hinnen and others first tested yeast transformation successfully in 1978, dozens of foreign genes such as human interferon gene, hepatitis B surface antigen gene, and -amylase gene have been expressed in yeast. A large number of domestic researchers have shown that the use of yeast to express antibacterial peptides is a feasible way. If the expression yield can be further improved, it will lay a good foundation for the early application of antibacterial peptides in clinical applications.

Physicochemical effects of antibacterial peptides

Natural antibacterial peptides are usually small, basic molecular polypeptides composed of more than 30 amino acid residues, which have good water solubility and a molecular weight of about 4,000 Daltons. Most antibacterial peptides are thermally stable, and their activity can be maintained by heating at 100 ° C for 10-15 minutes. Most antibacterial peptides have an isoelectric point greater than 7 and show strong cationic characteristics. At the same time, antibacterial peptides are more resistant to larger ionic strength and higher or lower pH values. In addition, some antibacterial peptides also have the ability to resist hydrolysis by trypsin or pepsin.

Antibacterial peptide function From the current research results, it is generally believed that the bactericidal mechanism of antibacterial peptides mainly acts on the cell membrane of bacteria, destroys its integrity and produces perforation, causing cell contents to overflow outside the cell and die. First, it is attracted to the surface of the bacterial membrane by electrostatic attraction. The hydrophobic C-terminus is inserted into the hydrophobic region of the membrane and changes the conformation of the membrane. Multiple antibacterial peptides form ion channels on the membrane and cause some ions to escape and die. Some scholars believe that antibacterial peptides act on membrane proteins to cause cohesion, inactivation and ion channels, causing changes in membrane permeability and leading to death. Some scholars have proposed whether antibacterial peptides have specific membrane effects and the synergistic effect of other factors. And other issues. The mechanism of action of different classes of antimicrobial peptides may be different.

Most antibacterial peptides have the characteristics of strong alkalinity, thermal stability, and broad-spectrum antibacterial. Some antibacterial peptides have a powerful killing effect on some fungi, protozoa, viruses and cancer cells.

Killing effect of antibacterial peptides on bacteria

Antibacterial peptides have a highly effective and broad-spectrum killing effect on Gram-negative and positive bacteria. At least 113 different bacteria have been reported at home and abroad that can be killed by antibacterial peptides.

Killing effect of antibacterial peptides on fungi

The first antimicrobial peptide with antifungal effect was Magainins isolated from the skin of amphibians frogs. It not only acts on G +, G-, but also kills fungi and protozoa. Defensins is an endogenous bactericidal peptide of animal cells. It is isolated from phagocytes and has a broad antibacterial spectrum. The killing effect on G + is greater than that on G-. It also affects fungi and some eukaryotic cells. cell. Cecropin A and its analogs such as cecropin-melitin hybrid peptide have a certain killing effect on fungi that infect insects.

Killing effect of antibacterial peptides on protozoa

The antibacterial peptide Magainins has a killing effect on the protozoa. Experiments have shown that antibacterial peptides can kill Paramecium, Amoeba and Tetrahymena. Tussah silkworm antibacterial peptide D also has a killing effect on Trichomonas vaginalis.

Killing effect of antibacterial peptides on viruses

Melitiin and Cecropins inhibit HIV-1 virus proliferation by suppressing gene expression at subtoxic concentrations. Magainin-2 and synthetic peptides Modelin1 and Moderln-5 have a certain inhibitory effect on herpes virus HSV-1 and HSV-2. These peptides act directly on the viral envelope rather than inhibit viral DNA replication or gene expression.

Killing effect of antibacterial peptides on cancer cells

Antibacterial peptides have no adverse effects on normal mammalian cells and insect cells, but have significant killing effects on cancer cell lines. This selective mechanism may be related to the cytoskeleton. The dose-related effects of antibacterial peptides on the killing effect of cervical cancer cells, rectal cancer cells and liver cancer cells have been reported.

Preventing sepsis

Natural antibacterial peptides have selective immune activation and regulation functions, and have good preventive and protective effects on sepsis. The abuse of traditional antibiotics has led to the emergence of various drug-resistant strains in the clinic, which seriously endangers human health. In the process of competition with pathogenic bacteria, antibacterial peptides from various sources in nature have become a new hope for people to develop new anti-infective drugs, but people's knowledge and research on antibacterial peptides still focus on its effect of directly killing bacterial growth. .

Septicemia is a critical illness caused by a bacterial infection accompanied by a systemic inflammatory response syndrome. Pathogenic microbial infection induces a large number of pro-inflammatory factors to be released, leading to the failure of a variety of important organs with a high mortality rate. Based on reptile cathelicidin antibacterial peptides and derivatives and their applications, it has been revealed that the antibacterial peptides have selective immune activation in vivo and in vitro. In animal models of sepsis induced by various standard and clinical resistant strains, cathelicidin peptides selectively activate the natural immune response in the body, while not stimulating the activation of a large number of harmful inflammatory factors, and selectively stimulate inflammation-inhibiting cells through the p38 MAPK signaling pathway The expression and release of factors and immune cell chemokines have a good preventive and protective effect on systemic and fatal sepsis. ^[1]

Development status of antibacterial peptides

So far, no less than 200 antibacterial peptides have been induced and isolated from different organisms, and more than 170 have been isolated from insects alone. People have classified according to the source and structural properties of antibacterial peptides. Antibacterial peptides can be classified into 5 categories based on their structure

Linear peptide with helical structure

Cecropins was the first animal antimicrobial peptide to be discovered. In 1980, it was isolated from Bombyx mori by Boman et al. This type of polypeptide antibiotic generally contains 37 to 39 amino acid residues and does not contain cysteine. Its N-terminal region has a strong basicity, which can form a nearly perfect amphiphilic helix structure, and a C-terminal region can form a hydrophobic helix. There is a hinge region formed between glycine and proline between the two, and the C-terminus of most polypeptides is amidated. Amidation plays an important role in its antibacterial activity. Since then, people have isolated cecropins antibacterial peptides from silkworm, tussah silkworm, fruit fly, and fly. In 1989, Lee et al. Increased cecropin P1 from the small intestine of pigs, indicating that cecropins may exist widely in animals. Cecropins have a strong lethality to the gram-positive and negative bacteria, but have no toxicity to fungi and eukaryotic cells. Currently cecropins have been artificially synthesized and commercialized.

Magainins is also an earlier class of antibacterial peptides with amphiphilic helical structure. Originally isolated from the skin of toads, analogs were later found in the nervous and intestinal tissues of mammals. Magainins has a killing effect on Gram-positive bacteria, negative bacteria, fungi, and protozoa, but its activity against Gram-negative bacteria is about 10 times lower than that of cecropins.

In addition, some peptides with helical structures were isolated from regenerative organs and various tissues and organs of amphibians in some animals, such as dermaseptin derived from South American frog and bombininh derived from tree frog.

Linear peptides rich in certain amino acids

Apidaecins are proline-rich polypeptide antibiotics isolated from honeybees. They generally contain 16 to 18 amino acid residues, of which proline content is as high as 33% and arginine content is as high as 17%. Apidaecins are highly active against some Gram-negative bacteria, but not against Gram-positive bacteria. The high lethality of apidaecins to certain Gram-negative phytopathogens and enterobacteriaceae, makes it very promising in plant antibacterial disease genetic engineering and food industry.

Drosocin is a proline-rich antibacterial peptide derived from Drosophila. It is structurally similar to apidaecins, but has an O-disaccharide chain (- N-acetylgalactosamine-galactose.)

Coleoptericin and hemitericin are derived from Coleoptera and Hemiptera insects, respectively. The primary structure is rich in glycine and generally has a large molecular weight. Oppenheim et al. Isolated a group of histidine-rich antibacterial peptides from human parotid and mandibular gland secretions, ranging in length from 7 to 38 amino acid residues, and are called histatins. Active against a variety of microorganisms that cause oral infections. Indolicidin is a peptide antibiotic derived from bovine neutrophils. It is named because it contains 5 tryptophan in 13 amino acids. Its C-terminus is amidated. It has strong bactericidal activity against E. coli and Staphylococcus aureus.

Peptide containing one disulfide bond

This is a very small number of antibacterial peptides. The first such peptide was found to be bactenecin, which is derived from bovine neutrophils. Its 12 amino acids contain 4 arginines, forming disulfide bonds between its 2 and 11 amino acid residues. bactenecin is active against both E. coli and Staphylococcus aureus. These peptides also include some peptide antibiotics derived from frog skin. Generally, there is a "loop" formed by 7 amino acids at the C-terminus and a long "tail" at the N-terminus, such as brevinin-1, brevinin-2.

Polypeptides containing two or more disulfide bonds

The typical representative of this type of polypeptide is defensins. The -defensins originally discovered are derived from mammalian tissues and generally contain 29 to 34 amino acid residues, of which 6 conserved cysteines form 3 intramolecular disulfide bonds. In addition, arginine at positions 6 and 15 and glycine at position 24 are also conserved. -defensins can form a three-layer -sheet structure, which is stabilized by three disulfide bonds and a salt bridge between Arg-6 and Glu-24. Currently, defensins have been synthesized and commercialized. Defensins have a killing effect on a variety of bacteria and certain fungi, and have certain toxicity to eukaryotic cells. Defensins are more active against Gram-positive bacteria than Gram-negative bacteria. defenssins are less active than cecropins and usually work at low ionic strength. -defensins are larger than -defensins and generally contain 38 to 42 amino acid residues. Both contain 3 disulfide bonds and 4 to 8 arginines. Insect defensins are similar to -defensins at the C-terminus, but there are only two -sheet structures with an alpha helix in the middle for stabilization, which mainly acts on Gram-positive bacteria, but not on fungi. Plant defensins generally have 45 to 54 amino acid residues, which can form 4 disulfide bonds, 3 beta sheet structures and an alpha helix structure. Plant defensins generally work on fungi but not bacteria. Different plant defensins have different antibacterial spectrum against fungi. Thionins are also a class of plant-derived peptide antibiotics that contain 45 to 47 amino acid residues and have 3 or 4 disulfide bonds formed by 6 or 8 cysteine residues. Its secondary structure can form two anti-parallel -helix structures and two anti-parallel -sheet structures. thionins inhibits a variety of phytopathogenic bacteria and fungi, but does not work against bacteria of the genus Pseudomonas and Erwinia.

Lantibiotics

Lanolin antibiotics (1antibiotics) refer to some peptide antibiotics produced by bacteria, which are synthesized in the ribosome by a gene code and processed after translation to contain some special organic groups. One of the most widely studied is nisin. It is an antibacterial peptide derived from lactic acid bacteria. The mature peptide is composed of 34 amino acids and contains special genes such as lanthionine and methyl lanthionine. It is mainly used for Gram-positive bacteria, but not for Gram-negative bacteria. It has been widely used as a food preservative. Research on the application of nisin and its analogs in medicine is also ongoing.

Application prospects of antibacterial peptides

At present, all conventional antibiotics have emerged corresponding drug-resistant pathogenic strains, and the problem of drug resistance of pathogenic bacteria has increasingly threatened people's health. Finding new types of antibiotics is an effective way to solve the problem of resistance. Antibacterial peptides are considered to have broad application prospects in the pharmaceutical industry because of their high antibacterial activity, wide antibacterial spectrum, many types, wide range of options, and the difficulty of target strains to produce resistance mutations. At present, a variety of peptide antibiotics are undergoing pre-clinical feasibility studies, of which magainins has entered the phase III clinical trial stage. Progress of some peptide antibiotics in medical research.

Company Peptide Clinical indication Stage of development

Magainin Pharmaceutical MSI-78 Impetigo Abandoned after phase III (1997)

MSI-78 Topical treatment of diabetic foot ulcers phase (1997)

Applied Microbiology / Astra / Merck Nisin (lantibiotic Gastric Helicobacter infection / ulcers Early clinical trails (1997); PhaseI (1998)

Applied Microbiology / Nippon / Shoji Nisin variants Vancomycin-resistant enterococci (parenteral) Preclinical research (1997)

Micrologix Biotech MBI-11CN + Gram-positive infection Preclinical research (1997)

MBI-20 series (-helical) Gram-negative infection; enhancers of conventional antibiotics Research and development (1997)

Intrabiotics IB367 (-sheet) Topical treatment of oral mucositis (muoth ulcerations) Preclinical research (1997); Phase I (1998)

Xoma Mycoprex (BPI-derived) Systemic candidiasis; enhancer of fluconazole activity Prelinical research (1997); Phasecompleted, Phase initated (1998)

Most clinical trials are now used for topical treatments, and this treatment should be safe and effective because some of the more toxic peptides and lipopeptides such as gramicidin S and polymyxin B have been used to make skin ointments . These peptides can also be used where conventional antibiotics and conventional therapies do not work. The use of powders to treat lung infections is a promising development direction. Oral drugs may be used to treat intestinal infections, and nisin is conducting clinical trials against Helicobacter. At least two companies are developing treatments for parenteral administration.

The application of antibacterial peptide genetic engineering in agriculture is mainly used to transform crops to cultivate disease-resistant varieties. Because antibacterial peptides have bactericidal activity against a variety of plant pathogenic bacteria, the introduction of anti-bacterial skin genes into human plants can be expected to improve their disease resistance.

Antibacterial peptide genes are used to transform crops to cultivate disease-resistant varieties, such as potato bacterial wilt resistance, tobacco bacterial wilt resistance, and rice leaf blight resistance.

Antibacterial peptides have no adverse effects on normal mammalian cells, but have obvious killing effects on cancer cell lines and some viruses. This indicates that antibacterial peptides have good application prospects in the treatment and prevention of cancer and antivirus.

As some peptide antibiotics have strong resistance to some plant pathogenic bacteria and fungi, some peptide antibiotics have been used in plant disease resistance genetic engineering. For example, Jaynes et al. Transferred two cecropin analog genes, Shiva-I gene and SB-37 gene into tobacco, and found that Shiva-I transgenic tobacco has certain resistance to bacterial wilt, while SB-37 transgenic tobacco does not have Resistance. Research by Huang et al. Showed that the fusion of cecropin-like polypeptide MB-39 gene with barley and amylase signal peptide genes was transferred into tobacco, and the resistance of the resulting plants to wildfire was enhanced. In China, Huang Danian and others used cecropinB gene to transform rice, and obtained some plants with different resistance to rice stripe disease.

Research on antibacterial peptide animal transgene has also made some progress. For example, genetic engineering can be used to block the transmission of some arboreal diseases. Studies by Possani et al. Have shown that the expression of Shiva-3 in mosquitoes can inhibit the spread of malaria, but There are still some difficulties in mosquito transgenic technology; Durasu1a et al. Significantly reduced the number of trypanosomes in their bodies by expressing CecropinA in the symbiotic bacteria of the red hunter. Reed et al. Transferred Shiva-Ia to mice, and the resistance of transgenic mice to Brucella was significantly enhanced, which provided new ideas for artificial breeding of new breeds of disease-resistant breeding animals. In addition, research on the application of antimicrobial peptides in food preservation, fresh flowers preservation and animal feed additives is also in progress.

Domestic research and development of antibacterial peptides

The antibacterial peptide, a product (lysozyme), which was artificially induced and extracted from the endemic species of China's endemic species, tussah and pupa, is a pioneering scientific research achievement obtained by more than ten years of work. Antimicrobial peptide pharmaceutical products are purified by bioengineering methods into a new class of drugs. It has a broad-spectrum bactericidal effect and can inhibit the replication of hepatitis B virus. Especially for drug-resistant bacteria, antibacterial peptides have a strong killing effect and can selectively kill tumor cells. It is a compound with a target and a new mechanism of action.

Nankai University, Tianjin University, and Dagang Oilfield joined forces to successfully isolate antibacterial peptides from flies that inhibit various pathogenic bacteria and viruses. At present, various bacteriostatic experiments have been completed, and researchers are working on further purification of antibacterial peptides extracted from fly larvae.

Zhang Yonglian and others from the Shanghai Institute of Biochemistry and Cells, Chinese Academy of Sciences made a breakthrough in the functional study of a new mouse-derived gene named Binlb (approval number: 39893320). This gene specifically expresses antibacterial peptides only in epididymal head epithelial cells, and it is the highest expressed during peak growth. This is the first natural antibacterial peptide related to the epididymis defense system, which is similar to the human body. It is also the first functional gene discovered in the world to be related to inflammation of the male reproductive system. It is the first time that the epididymis has an immune system. His research result: "An antibacterial peptide gene in the rat reproductive system" was published in "Science" in March 2001. It is the first time that the basic research results of life sciences in China have been published in "Science".

Research on the transformation of silkworm antibacterial peptide B gene by rice hosted by Professor Huang Danian of the Chinese Rice Research Institute A new approach was introduced. This gene can be introduced into popular varieties to obtain excellent agronomic traits. In addition, the second-generation transgenic plants still show resistance to bacterial leaf blight and thin stripe disease.

Researcher Jia Shirong of the Biotechnology Research Center of the Chinese Academy of Agricultural Sciences completed the synthesis of the antimicrobial peptides Cecropin B and Shiva A, constructed expression vectors, and successfully introduced these genes into seven major potato varieties (lines) in China, and obtained 1,050 transgenic strains. Lines, after years of multi-point disease resistance identification, three disease-resistant strains were initially screened.

Huang Yadong, Zheng Qing, Wang Linchuan, Liao Fuping, Huang Ziran, etc. used the viral vector pAcGP67B to delete the start code ATG of the silkworm antibacterial peptide gene by PCR point mutation technology in order to form the coding sequence of the signal peptide excision site. The insertion of gp67 signal peptide can guide the secretion of the expression product to the outside of the cell and facilitate the identification of the expression product and the determination of its biological activity.

Antibacterial peptide replacement

^[4]

Peptide Lisheng

The antibacterial peptide industry is an emerging high-tech bioengineering and biotechnology industry. Due to the imperfect early bioengineering methods, the extraction of antibacterial peptides is extremely expensive, limiting its application in medicine, agriculture, and industry. With the further development of transgenic technology, it is now possible to use engineering bacteria or yeast for mass production of antimicrobial peptides, but its core technology is only mastered by a few scientists and companies. Its market is widely used in agriculture, it can be used as feed additives, and suitable for raising various animals; in medicine, it can be an excellent substitute for antibiotics, and it is also considered as a promising drug to overcome cancer and AIDS in the future; It can be used as a green preservative; in human life, it can be used as a substitute for health products and antibacterials.

In the bidding guide on the industrialization of feed antibacterial peptides issued by the Ministry of Science and Technology of China in June 2007, it was mentioned that for the current situation of large-scale production of feed antibacterial peptides at home and abroad, the establishment of improved and efficient expression of antimicrobial peptides for feed And fermentation production technology, we have developed new antibacterial peptide products for feed. "The application of antibacterial peptides in the field of veterinary drugs and feed additives has shown that the antibacterial peptides are fully capable of replacing antibiotics. ^[5]

Summary of antimicrobial peptides

^{[6] There} are still some issues that need to be resolved for antimicrobial peptides to become drugs. The first problem is the source. Due to the limited natural resources of insect antibacterial peptides, chemical synthesis and genetic engineering have become the main means of obtaining antibacterial peptides. Chemical synthesis of peptides is costly. However, through genetic engineering, the direct expression of antibacterial peptide genes in microorganisms may cause host microorganisms to commit suicide without obtaining expression products. Although the expression of the antibacterial peptide gene in the form of a fusion protein can overcome this shortcoming, it still has the problem of low expression products. Although the antibacterial peptide maganin from frog skin has entered clinical phase II and phase III experiments as a genetically engineered drug, it is believed that antibacterial peptides may be commercialized only if the price is less than $ 10 per gram. Therefore, how to improve the production efficiency and reduce the cost of antimicrobial peptides is a problem that must be solved in the application of antimicrobial peptides. Secondly, compared with traditional antibiotics, the antibacterial activity of insect antibacterial peptides is not ideal. Transforming existing antimicrobial peptides and designing new antimicrobial peptide molecules are effective ways to create highly active antimicrobial peptides. This requires further research on the relationship and mechanism of antimicrobial peptide structure and activity, and provides sufficient theoretical basis for the transformation and design of antimicrobial peptide molecules.