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Transfer of biological fermentation technology

产品编号: P0136730 CAS号:
分子式: 分子量:
EIENCS:    
First, transfer DHA algae oil efficient extraction technology
Medicine, food, feed
[summary of the project] at present, there is a high efficiency extraction technology of DHA algae oil to be transferred, through fermentation-wall breaking, and then directly into the centrifuge to extract oil, saving the middle press-spray-leaching, the specific technical indicators can be discussed in detail after contact.
[project advantage] can save a lot of intermediate links, roughly reduce the production cost of 7000 yuan per ton.
[technical indicators] specific technical indicators can be discussed in detail after contact.
[expected benefit] the results of this project will significantly improve the domestic lipase production technology level, has important popularization and application value, and the economic benefit is considerable.
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
II. Transfer of lysozyme strains and fermentation techniques
[technical field] Food, feed
[summary of the project] transfer of intracellular lysozyme fermentation extraction technology,
[project advantage]
[technical index] fermentation level: 4 grams per litre; enzyme activity in fermentation broth: 160000 units
[expected benefit] the results of this project will significantly improve the domestic lysozyme production technology level, has important popularization and application value, and the economic benefit is considerable.
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
Third, tylosin and super tylosin
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
Feed [technical field]
[summary] Tyroxin is a hexadecyllactone antibiotic, which is composed of A, B, C and D components obtained by Streptomyces freund in the fermentation process. Group A is divided into tylosin (Tylosin), B component, decarbonized sugar tylosin ((Desmycosin), C component, nystatin (Macrosin), D component, raloxins (Relomycin) and structure analogues. Among the above four components, all the components except raloxin had antibacterial activity in vitro, while tylosin ((A component) had high activity in vivo. Tylosin is white or yellow-white amorphous powder, melting point 128 ≤ 132 ℃, weakly alkaline, pH 7.1, slightly soluble in water, easy to dissolve in polar organic solvent, molecular weight 915, chemical formula C46H77NO17. Tylosin and inorganic or organic acids can form salt soluble in water. Tartrate and phosphate are often used, in which the chemical formula of tylosin tartrate is (C46H77NO17) 2C4H6O6 with molecular weight of 19871, and the chemical formula of tylosin phosphate is C46H77NO17 ·H3P04 with molecular weight of 1014.11.
The following dosage forms are common in the market: tylosin tartrate (original powder), tylosin phosphate (original powder), 8.8% tylosin phosphate granule, 22% tylosin phosphate granule, 27.8% tylosin phosphate granule, tylosin tartrate soluble powder and so on. Downstream products include: temicoxin, tylosin, acetylisovalyl tylosin and so on.
[project advantage] the fermentation level is high and the cost is low.
[technical index] strain technical level fermentation unit 11000u/ml fermentation cycle 170 h fermentation index 55 million / hm3 original powder yield 75% super tylosin: titer 21000 u ·ml, cycle 150 hours, conversion 85% ≤ 90%, production cost 600 × 650 yuan / 1 billion.
[expected benefit] the results of this project will significantly improve the production technology level of tylosin in China, which has important popularization and application value, and the economic benefit is considerable.
[status of awards and patents]
[technology maturity] maturity scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
 
Fourth, transfer pyruvate biological fermentation technology
 
[technical field] Pharmacy
[project overview]
Pyruvate (Pyruvic acid), also known as 2-oxopropionic acid (2-oxopropanoic acid), α-ketopropionic acid (α-ketopropionic acid) or acetylformic acid (Acetylformic acid),) is one of the most important organic acids. It has a wide range of applications in pharmaceutical, food, chemical, agrochemical and other fields, as well as in scientific research. Pyruvate plays a very important role in biological energy metabolism. Pyruvate series derivatives, including methyl pyruvate, ethyl pyruvate, pyruvate creatine, calcium pyruvate, potassium pyruvate, sodium pyruvate, magnesium pyruvate and so on, are widely used in medicine, chemical industry and other fields, and are also raw materials for a variety of chemical products, pesticides and so on.
 
[project advantage] through the construction of a new type of E. coli engineering bacteria, the high conversion fermentation of pyruvate from glucose was realized. This method is green, environmentally friendly, sustainable, economically competitive, and has a good industrial application prospect.
[technical index] at present, at the level of 5L fermenter, through batch feeding, the yield of pyruvate can reach about 70g/L, basically without by-products, and the conversion rate is 0.8g pyruvate / g glucose.
[expected benefit] according to the current technical level, the comprehensive cost of pyruvate production is estimated to be about 25000 yuan / ton, and the current market price is about 50, 000 yuan / ton. Based on the production scale of 1000 tons, the gross profit can reach 25 million yuan per year.
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
Fifth, transfer of two antimicrobial peptide production strains and fermentation techniques
 
Feed [technical field]
[summary of the project] one of the two antimicrobial peptides is negative bacteria, such as Escherichia coli and Salmonella. The output reached 2g/l. (transfer price 2 million) one strain is positive bacteria, such as Staphylococcus aureus, Clostridium perfringens (Clostridium weisei), the yield of which is up to 3.5g/l. (transfer price 1 million)
 
[project advantage] 1. Evaluation of bacteriostatic concentration in vitro (minimum inhibitory concentration, MIC)). 2.
2. Evaluation of animal culture experiments (mainly pigs and chickens). The effect of anti-diarrhea is very significant. The effect on daily weight gain and feed to meat ratio is the same as that of antibiotics, or even better. The molecular weight is between 2-5kDa and the amino acid sequence has been confirmed. In line with the current national limited resistance environment, antimicrobial peptides have a good industrial application prospect.
[technical index] Molecular weight of antimicrobial peptides: 2-5kDa
G+ antimicrobial peptides: production of 3.5g/l
G-antimicrobial peptides: production of 2g/l
 
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
VI. Transfer of the highest level of D-ubiacyllactone hydrolase bacteria and calcium pantothenate technology in China
Feed [technical field]
[project overview] D-ubiacyllactone hydrolase
[project advantage] enzyme activity is high and immobilization is stable.
[technical index] calcium panthenate enzyme activity, 60U/g dry weight, biomass 50g/L dry weight, conversion rate 92%, hydrolysis product D pantoic acid ee value 98.3, immobilization data conversion rate about 90%, prolongation time to 18 h can reach 97%. Immobilization we have done 20 times, but also kept more than 90% conversion, fermentation cycle about 30 h
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
7. Transfer of A82846B intermediate A82846B fermentation technology and LY333328 synthesis technology
 
Medicine [in the field of technology]
[summary] oritavancin,LY333328 is a new semi-synthetic glycopeptide antibiotic, which acts in the same mechanism as vancomycin and teicoplanin, that is, inhibiting the biosynthesis of cell wall of strain G. Its antibacterial spectrum is wide, including Staphylococcus aureus, Enterococcus, Streptococcus, Corynebacterium brevis and Clostridium vulgaris and so on. Good results have been achieved in the treatment of skin and soft tissue infections.
 
[project advantage] Intermediate A82846B has high yield and can be mass produced.
[technical Index] 1 Intermediate A82846B
Fermentation level: 1 g / L,
Fermentation time: 9 × 10 days,
Production strain: Nocardia orientalis,
Extraction yield: 50 ≤ 60%
 
2 Olivan star semi-synthesis
Yield: 60 per cent
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
 
VIII. Provide egf (recombinant epidermis growth factor) fermentation technology and strain
Medicine [in the field of technology]
EGF (Epidermal Growth Factor) is a peptide chain composed of 53 amino acid molecules, which contains 6 cystine molecules and forms stable disulfide bonds between cysteine molecules, making the whole peptide chain become the active substance of three circular parts. The main function of EGF (Epidermal Growth Factor) is to promote the proliferation and differentiation of skin cells and accelerate the repair of injured epidermis cells. Accelerate metabolism and increase the proportion of new cells in the skin, it can delay the aging of skin cells and make the skin moisturize and smooth. There are also inhibition of gastric acid secretion and other special effects, in medicine has a wide range of uses.
 
[project advantage] High fermentation level and mass production.
[technical index] strain: Escherichia coli or yeast
Fermentation level: 1 g per litre
Fermentation cycle: 24 hours
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
IX. Transfer of vitamin B12 strains and fermentation technologies
Feed [technical field]
Vitamin B12b is one of the two active coenzyme forms of vitamin B12 in vivo. Vitamin B12b is involved in important metabolic reactions in vivo (such as nucleic acid synthesis, amino acid, protein, fat metabolism, etc.). It is also a necessary substance to promote cell growth, proliferation and maintain the integrity of myelin sheath of nervous system. The technical improvement of fermentation and extraction of the project, through a large number of experiments, statistics, analysis, in a good management state, can fully achieve the desired goals. All the indexes of B12 project products meet the relevant requirements of feed additives, the technology is mature, and the implementation feasibility is strong.
[project advantage] High fermentation level and mass production.
[technical index] the latest fermentation cycle in 2018 is 186 to 200 hours, the fermentation level is 260 mg / L, and the cost is 10 yuan per gram.
[expected benefit] after the implementation of the project, the annual output of vitamin B12 (equivalent to pure products) 6 tons, annual sales up to 200 million yuan, profits and taxes up to 15.36 million yuan, annual foreign exchange earned 36 million US dollars.
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
 
X. transfer of novel MATE expression system of Bacillus subtilis with high expression of hetero-proteins
 
[technical field] research
[summary] Bacillus subtilis (Bacillus subtilis), as a model strain of Gram-positive bacteria, has many excellent characteristics, such as secretory expression, simple and easy fermentation and culture, high heterogenic expression level (20 × 25 g ·L) and safety, so it is considered to be an ideal protein production strain, which is widely used in the research and development of various enzyme proteins. At present, there are few commercial expression systems for Bacillus subtilis, and there is a lack of efficient expression system of Bacillus subtilis with independent intellectual property rights in China, and there are some restrictive factors in the existing expression systems of Bacillus subtilis, such as insufficient start-up intensity, high price of inducers, toxic effects of antibiotics or antibiotics on cells, and so on. It limits its practical application potential in research institutions and magnified production.
[project advantage] as a new type of high efficiency protein expression system, MATE system has realized the high expression and exocrine expression of alpha- amylase, beta- mannanase, aloxanose isomer, beta- oligogalactosidase, creatine enzyme, creatine enzyme, DAA, green fluorescent protein, luciferase, human fibroblasts growth factor FGF21 and so on. The expression of target protein accounted for 60% of the total protein, and the expression of extracellular target protein was more than 80%. At the same time, MATE system can be used as gene switch (Gene Switch) to accurately regulate the induced turn-on and shutdown (ON/OFF) of the target gene, and to realize the regulation and optimization of host metabolic pathway. The new MATE protein expression system has the advantages of high expression, high secretion, food grade safety, flexible regulation and so on. It has a very wide application potential in the expression and industrial production of enzyme protein, pharmaceutical protein and other high value-added proteins. At the same time, it fills up the problem of high efficiency expression system of Bacillus subtilis, which lacks independent intellectual property rights in China.
[technical index] the latest fermentation cycle in 2018 is 186 to 200 hours, the fermentation level is 260 mg / L, and the cost is 10 yuan per gram.
[expected benefit] at present, the use of efficient protein expression system to produce high value-added protein products such as pharmaceutical protein has a wide prospect, and the market size is expected to exceed US $200 billion. Bacillus subtilis can also be widely used as living bacteria in agriculture, animal husbandry and other fields. The new expression system of Bacillus subtilis, which we independently developed, will be widely used in scientific research institutes and biotechnology enterprises at home and abroad. The conservative direct market value is 50 million yuan, and the value of terminal products is estimated to be more than 5 billion.
 
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
 
Xi. Transfer of 5-aminolevulinic acid (5-amino levulinic acid,ALA) fermentation technology
Feed [technical field]
[summary of the project] 5-aminolevulinic acid, also known as 5-amino-4-ketovalic acid, is a natural functional non-protein amino acid in organisms. It is an essential precursor for the biosynthesis of tetrapyrrole compounds such as heme, chlorophyll, vitamin B12 and so on. It has an important impact on plant photosynthesis and cell energy metabolism. ALA is widely used in medicine, pesticide, chemical industry and other fields because of its biodegradable and non-toxic and non-residual advantages. ALA has the function of plant growth hormone, which can promote the growth of crops, fruit trees, vegetables, garden plants, increase the yield and improve the quality of crops, and the effect of increasing crop yield can reach 10 ≤ 60%. In the field of feed, it can improve anemia and improve the immune ability of animals such as livestock. In medicine, ALA can be used as a new generation of photodynamic drugs for cancer diagnosis and treatment. ALA is also used as an additive for cosmetics and health foods.
[project advantage] this project has constructed a new type of engineering bacteria, the index has been much higher than the highest level of other existing technologies, the fermentation level exceeds 50 g / L, reaching the international leading level, completed the tonnage pilot test, the cost is less than 100000 yuan / ton, equivalent to one tenth of the existing chemical method.
[technical index] fermentation level 50 g / L, fermentation cycle 30 hours
[expected benefit] at present, the factory price of industrial grade ALA is about 4 million / ton, and the purity of 98% is 1700-19 million yuan / ton. The ALA biological manufacturing technology developed by us is expected to reduce the production cost to less than 100000 / ton, and the profit margin is very high. If 50 tons / year demonstration plant is built within 2 years, including 20 tons of pharmaceutical products and 30 tons of agricultural products. The profit is 16.8 million yuan / ton for medical grade and 3.95 million yuan / ton for agricultural grade, and the total profit can reach 450 million yuan. With the decline of production costs and the promotion of agriculture, the total profit is more than 10 billion yuan.
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
12. Transfer of "Technology of producing rare Panax Ginseng by microbial fermentation"
Medicine [in the field of technology]
[summary of the project] Panax ginseng is a general term isolated from ginseng and its plants (such as Panax quinquefolium, Panax notoginseng, etc.). It is the main active ingredient of Panax ginseng and has many physiological functions and medicinal value. Such as anti-tumor, immune regulation, protection of cardiovascular and cerebrovascular system, protection of nervous system, reduction of liver injury, anti-oxidation, anti-fatigue, anti-aging, promoting wound healing, relieving Alzheimer's disease, improving myocardial ischemia, anti-thrombus and other functions, can be widely used in drugs, health food and cosmetics. Shenyi capsule, a new anticancer drug (Rg3), is the first kind of anticancer drug to be listed in China. Drugs with proto-panaxadiol (PPD) and CK as raw materials have also entered clinical trials, and a large number of health products with various ginsenosides as the main components are on the market.
[project advantage] 1. The platform technology of biosynthesis of ginseng glycosides was established in yeast, on the basis of which a variety of rare ginseng saponins, including saponins and rare ginseng saponins, could be further produced.
2. The purity of the product is high, up to 99.9%, which is especially beneficial to the development of new drugs.
3. The cost is low, at present, the raw material cost of 10L level fermentation is only about 5 yuan / g product;
4. the yield is high, and yeast is a mature engineering bacteria system, and the potential for further optimization and improvement of yield is great.
5. has independent intellectual property rights and has so far applied for five patents;
6. the fermentation process is safe and controllable, and any external pollution such as pesticides is avoided.
7. Not limited by the source of plant raw materials, to avoid the depletion of valuable natural resources.
 If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
[technical index] at present, a number of products have completed the fermentation experiment of 10L fermenter. Within 96 hours of fermentation,
The yield of original panaxadiol can reach 11 g ·L, and the purity is more than 99.9%.
The yield of CK was 3 g ·L and the purity was more than 99.9%.
The yield of Rh2 was 2 g ·L and the purity was more than 99%.
The yields of Rg3, Rh1 and F1 were all more than 2 g ·L ~ (- 1).
[expected benefit] at present, the price of ginseng with good quality on the market is about 500 yuan / kg, the price of total saponins of its active ingredient extract is about 10, 000 yuan / kg (purity > 80%), the price of original panaxadiol with purity of 90% is about 200000 yuan / kg, and the price of Rh2 and CK with purity of 98% is more than 1 million yuan / kg, The whole market of ginseng related products in China has reached billions of US dollars.
[status of awards and patents]
1. A group of glycosyltransferase and its application, patent No. ZL 201310658887.9, has been authorized by China and has submitted patent applications for patents in the United States, Europe, Japan, Korea, India, Canada and Hong Kong.
2. Several preparation methods of rare ginsenosides, patent application No. 201410199461.6, are currently under substantive examination.
3. Nicotine adenine dinucleotides-cytochrome P450 reductase and its application, patent application No. 201510095010.2, currently under substantive examination.
4. Glycosyltransferase mutant protein and its application, patent application No. 201510051992.5, currently under substantive examination.
5. A group of glycosyltransferase catalyzed by sugar chain extension and its application, patent application No. 201510313727.X, currently under substantive examination.
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
XIII. Transfer of cold gel and available gum fermentation technology and high-yield strains
Feed [technical field]
[project overview]
[project advantage]
[technical index] cold gel, fermentation cycle 48 hours, gum yield 1.8%, high acyl group yield 85%, low acyl group clarification yield 60%, low acyl group yield 80%, product index higher than all domestic products, similar to foreign countries; available gum, fermentation cycle 72 hours, gum yield 3.8%, yield 80%, fine product 70%, strength 450 above 450
 
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
 
14. Rearrangement of Escherichia coli nucleoglycolic acid pathway to develop a new type of plasmid-free engineering bacteria with high thymidine production
Medicine [in the field of technology]
Thymidine, composed of deoxyribose and thymidine, is the precursor of stavudine, zidovudine and other antiviral drugs. At present, Bacillus subtilis and Corynebacterium can be used to produce bacteria. Researchers from ForBioKorea Company and BioNgene Company in Korea constructed a plasmid-free engineering strain with high thymidine production based on E.coli BL21 site strain.
 
Through genome recombination engineering, 11 target genes deoA tdk udp ung purR pepA argR rpoS deoD deoCAB, were knockout and 7 other genes tdI were knockout (T 4) nrdCA nrdB udk-dcd,) to obtain the excellent phenotype of high thymidine production and rarely accumulation of deoxyuridine.
 
The gene expression characteristics of engineering strain HLT013 and original strain E.coli BL21 were compared and analyzed by DNA microarray technology. based on the results of microarray analysis, pyr synthetic genes and 10 other genes were overexpressed in HLT013 to find candidate targets to improve thymidine yield. The results showed that bacteriophage shock protein A (PspA) significantly promoted the production of thymidine by reducing the pressure of redox. The PspA gene was integrated and overexpressed in HLT013. After 120 hours of batch feeding fermentation, the thymidine yield of the engineering strain HLT026 increased by more than 30% to 13.2g/L. This study has shown that it can not only overexpress the target gene, but also reduce the severe redox imbalance pressure in the cell.
 
In addition, it was also found that the promoters of carA/B gene were co-regulated by PurR, PepA and ArgR transcription factors, and blocking these three transcription factors could increase the yield of thymidine.
 
Many developed industrial strains, the culture of plasmid-free engineering strains is stable and convenient. A plasmid-free engineering strain without thymidine overexpression was developed by using E. coli genome recombination engineering, which has many benefits. [project advantage] this project has constructed a new type of engineering bacteria, the index has been much higher than the highest level of other existing technologies, the fermentation level exceeds 50 g / L, reaching the international leading level, completed the tonnage pilot test, the cost is less than 100000 yuan / ton, equivalent to one tenth of the existing chemical method.
[technical index] the fermentation period is 90 hours, and the yield of 10g/l at fermentation level is 65 ≤ 70%.
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
 
XV. Provision of L-dopa fermentation techniques and strains
Medicine [in the field of technology]
[summary of the project] the chemical name of 3, 4 dihydroxyphenylalanine (L-DOPA) is 3, 4-dihydroxyphenylalanine. As an important bioactive substance, L-DOPA is an important intermediate product in the biochemical metabolic pathway from L-tyrosine to catechol or melanin. Dopamine, a derivative of L-DOPA, is an important neurotransmitter. Because dopamine can not enter the brain tissue through the blood-brain barrier, it can not be treated with dopamine supplementation. L-DOPA can form dopamine through the blood-brain barrier and decarboxylated in the brain tissue, thus increasing the content of dopamine in the brain tissue to achieve the purpose of treatment. Birkmayer was effective in the treatment of PD with levodopa in 1961. Developed by Roche, its preparation, Medoba, was first listed in Switzerland in July 1973. So far, it is still one of the most effective drugs for Parkinson's disease.
 
L-DOPA can also be used to treat amblyopia; L-Tyrosine can be transformed into melanin by L-DOPA, which can be used for hair staining; in addition, L-DOPA has been found to have anti-aging effect. The biosynthesis of L ≤ DOPA by microbial enzyme method has the advantages of short production cycle and continuous mass production. In 2005, the annual output of L-DOPA in the world was about 250t, most of which were synthesized by microbial enzyme biosynthesis.
Tyrosinol lyase, also known as β-Tyrosinase, with PLP as coenzyme, TPL can catalyze the β-elimination of L-tyrosine to phenol, pyruvate and ammonia. Because this reaction is reversible, catechol can be used instead of phenol to form L-DOPA from catechol, pyruvate and ammonia catalyzed by TPL.
 
In this project, the gene fragment encoding TPL was transferred into E. coli for high density fermentation, and a large number of Tyrosinol lyase was obtained. L-dopa was synthesized from catechol pyruvate and ammonia catalyzed by TPL.
[project advantage] at present, the technical index of this project is about 24 hours of fermentation wet bacterial weight 100g/L, about 20 hours of biotransformation reaction, and the concentration of 50g/L is about 20 hours.
Index: the amount of bacteria in the transformation reaction was 5%, the concentration of the product was above 50g/L, the conversion rate was 90%, and the purification yield was 80%. The wet weight (crude enzyme) of fermented bacteria was about 100kg/t. The cost of 1t fermentation broth (including raw materials, labor and energy consumption) is about 2400 yuan.
[technical index] L-dopa (E. coli genetically engineering bacteria, enzyme production) transformation time: 24h+20~24h (enzyme transformation), fermentation level 45g/L about 80% yield
[expected benefits]
Table 1 cost estimation of conversion reaction solution
Reagent Unit price (yuan / Kg) Dosage (Kg) Total price (yuan)
Catechol 27.5 31.02 853.05
Pyruvate 50 24.81 1240.5
Ammonium sulfate 1.0 37.23 37.23
Wet bacteria 20 60 1200
Total
 
3330.78
L-dopa
40
As shown in the above table, the cost of 40kg product is about 83. 27 yuan / kg (including the total cost of fermentation and raw material cost of conversion reaction), and the cost of separation and purification, energy consumption, labor and so on is also calculated according to 83. 27 yuan / kg, that is to say, the production cost of L-dopa is estimated to be 166.54 yuan / kg. At present, the price of L-Doba is about 400 yuan / kg.
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
XVI. New biocide and preservative Roygl
Feed [technical field]
At present, most of the fungicides and preservatives used in the market are toxic chemical reagents, and the anticorrosion application in biological products such as food and feed is limited, so the price period of many biological products is obviously shortened, which hinders the market sales of the products.
In this technology, a new type of lactic acid bacteria approved by the state is used as a strain. Through the in-depth study of the metabolic process, it produces a new antibacterial substance, Royce, which can inhibit the growth of other pathogenic microorganisms at a very low concentration. This substance is an effective non-antibiotic type broad-spectrum antibacterial substance. Roysin has a wide range of potential applications in biological fungicides, anti-infection therapeutic agents, biological cross-linking agents, precursors of new biomaterials and so on. It can be widely used in the anticorrosion of food, feed, beverage and so on, and improve the price period of the product. Because the bacteria is approved by the state for food applications of lactic acid bacteria, so the safety can be fully guaranteed.
Because Royce is not only broad-spectrum antibacterial, but also harmless to humans and animals, its application is gradually being widely developed, such as as a biological preservative to prolong the price period of sausage, frozen food, etc.; as a biological sterilizer, for sterilization of food milk and biomaterials that can not be sterilized at high temperature; as an additive for infant food, to regulate the distribution of intestinal flora in infants. As an additive of gum, it is used to kill oral pathogenic bacteria to prevent dental caries; as an anti-infection therapeutic agent, instead of antibiotics, it is used to treat diseases caused by animal pathogens. BioGaia of Sweden has developed a series of probiotics containing the bacteria, which are sold worldwide to improve human and animal health. The Ministry of Health of our country also approved the lactic acid bacteria as a probiotic strain of health food in 2003.
[project advantage] the culture and transformation process of the strain has been developed, and the products can be put out for test.
[technical indicators]
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
[mode of cooperation] Cooperative development, technology transfer or joint production.
[photo of results] A brief introduction
 
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
XVII, β-carotene
Feed [technical field]
[summary of the project] β-carotene is a precursor of vitamin A, which can be used as a natural pigment in orange juice drinks and lipstick. It also has the effect of stimulating immunity, preventing carcinogenesis and preventing cardiovascular disease. The research results of this project are to produce safe and high yield β-carotene and lycopene by optimizing fermentation medium and fermentation process by (Blakelea trispora) fermentation of Brucella trisporium, and ultrasonic crushing method is used to assist extraction, which has a good development prospect. "
[project advantage] this project has constructed a new type of engineering bacteria, and the indicators have been much higher than the highest level of other existing technologies.
[technical index] cycle 168 h, fermentation level 2.5 ≤ 3.0 g ·L, yield 65%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
 
Eighteen, PQQ (pyrroquinolone quinones)
Feed [technical field]
[summary of the project] PQQ, as a new water-soluble vitamin, is a redox enzyme cobase, which is very rare and exists in some microorganisms, plants and animal tissues. It is not only involved in catalytic redox reactions in organisms, but also has some special biological activities and physiological functions (such as shortening the delay period of Acetobacter aeruginosa [Acetobacter rancens] and Saccharomyces cerevisiae [Saccharomyces cerevisiae], stimulating the early germination of tobacco seeds. Biological functions such as the prevention and treatment of certain diseases). Trace amount of PQQ can improve the metabolism and growth function of biological tissue, which is extremely valuable.
[project advantage]
[technical index] fermentation unit: 1 ≤ 2 g / L, fermentation time: 240 hours, extraction yield: 40%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
Nineteen, averamicin (Streptomyces pigmentosa) 280h, 33003800U / ml more than 80%
Feed [technical field]
[summary of the project] also known as abamphenicol, humithromycin,
 阿维拉霉素(avilamycin,简称 AVI)又称为阿维霉素、卑霉素,是由绿色产色链霉菌Tü57( Streptomyces viridochromogenes Tü57)发酵生产的甲基羟基甲氧基苯甲酸(DCIEA)的一种酯,同扁枝衣菌素类(eveminomycins)、居拉霉素类(curamycins)及火把霉素类(flambamycins)都属于正糖霉素族(orthosomycin,又译作奥尔托索霉素)的寡聚糖类抗生素。卑霉素已被证实对多种革兰氏阳性菌有抑制作用,包括一些致病菌,如万古霉素拮抗的肠道球菌,甲氧苯青霉素拮抗的葡萄球菌以及青霉素拮抗的肺炎双球菌,但对革兰氏阴性菌的抑制效果差。此外,卑霉素对大肠杆菌有一种间接作用,即它可以影响细菌鞭毛及细菌的粘附,并通过抑制细菌粘附于宿主粘膜细胞表面而达到抑制细菌的感染,从而抑制了疾病的感染。发酵主要的原料是:黄豆饼粉、淀粉、葡萄糖、硫酸镁、碳酸钙等,提取采用发酵液直接喷雾干燥法,然后添加重质碳酸钙,配制成 10%含量的预混剂。
 
[project advantage]
[technical index] fermentation cycle: 260 × 300 h, fermentation unit: 3 ≤ 4 g ·L, extraction and direct addition of CaCO3 spray drying to 10% premix
[expected benefits]
[status of awards and patents]
[technical maturity] pilot test or above
Technology transfer [through cooperation]
[photo of results] A brief introduction
 If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
  
 
Twenty, latromycin.
Feed [technical field]
[summary of the project] Letromycin (Laidlomycin), chemical name: 9-hydroxyl-β-(1-oxo-complex oxyl)-2-[5 ≤ N-tetrahydro-5-[tetrahydro-3 ≤ N methyl-5 [tetrahydro-6-hydrogenation-6-[(1-oxo-propioxyl) N-methyl]-3, 5-dimethyl-2-hydropyran-2-yl]-2-furan]-α, γ, 2, 8,-tetra-hydrogenated-1, 5-dimethyl-2-hydro-pyran-2-furan]-α, γ, 2, 8,-tetra-hydrogenated-1, 5-dimethyl-2-hydro-pyran-2-furan]-α, r, 2, 8, 8, 6-spiral dioxane-[4, 5]-decane-7-butyrate potassium salt.
Letromycin is an antibiotic produced by Streptomyces aeruginosa, which is produced by microbial fermentation and solvent extraction technology. the product adopts the patented technology and producing bacteria provided by us, and the main equipment is fermenter, extraction separator, concentrator and so on.
[project advantage]
[technical index] (Streptomyces aeruginosa) 270290h, 20000u ≤ ml ≥ 70%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
21, daunorubicin
Medicine [in the field of technology]
Daunorubicin is a very important antitumor drug in anthracycline antibiotics. The chemical name is 9-acetyl4-methoxyl-7,8,9, 10-tetrahydro-6, 9, 9, 11 ≤ 7, 12-Naphthalene Diketone. Daunorubicin is an orange-red needle-like crystal or amorphous powder, which is used clinically as its hydrochloric acid.
Molecular formula: C27H29NO10 molecular weight: 527.53
Introduction of production strains
The fermentation strain was Streptomyces, and the high yield daunorubicin strain was selected by mutation.
The fermentation level was 3 ±0.3g per liter of fermentation broth.
 If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
Medical use
 
Daunorubicin is mainly used in the treatment of acute leukemia. Daunorubicin can be used as the first choice for acute lymphocytic leukemia and acute myeloid leukemia. Daunorubicin can be used in combination with other drugs in the treatment of tumor diseases such as lymphosarcomas, neuroblastomas, rhabdomyosarcoma and so on.
 
General situation of the market
 
Because daunorubicin can also be used as a raw material for the chemical synthesis of doxorubicin and doxorubicin, the international market price is now about US $27000 per kilogram.
The main domestic manufacturers are: Zhejiang Haizheng Pharmaceutical Industry is the largest.
The main foreign manufacturers are: Italian Farmathia Puqiang Co., Ltd., Germany Farasiapuqiang Company and so on.
[project advantage]
[technical index] fermentation cycle: 210 hours, fermentation unit: 2.0g / L, total yield: more than 30%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
22, Tyrosine
Feed [technical field]
[project overview]
[project advantage]
[technical index] (Escherichia coli + yeast = enzyme + pyruvate fermentation broth + ammonia) 20 h (enzyme) + 45? 50 h? 8 h, 70 g? L 30% 55? 70? 80%?
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
23, doxacin
Feed [technical field]
【项目概述】多拉菌素为20 世纪90 年代由美国辉瑞公司研制开发的新一代大环内酯类抗寄生虫药,由突变的阿维菌素链霉菌生物合成,(Goudie A.C., et al, 1993)其最早上市于巴西和南非。(Vercruysse J., et al, 1993)与伊维菌素相比,多拉菌素在动物体内的消除率较低、生物半衰 期较长、生物利用率较高,(Atta A H., et al,2000;Perez R., et al,2002; Rubén Pérez et al,2008)而且多拉菌素肌肉注射刺激性小,给药方便,持效期更长,一次给药即可兼杀动物体内的线虫和体外寄生虫,不需要重复给药,因此广泛应用于养猪业和宠物业。最早发现它驱杀寄生 虫能力是在驱鼠继代的蛇形毛圆线虫和杀兔痒螨的动物模型中。多拉菌素对牛、马和骆驼的多种胃肠道线虫、体外节肢动物具有极佳的驱杀效果,尤其对猪消化道线虫、猪消化道圆虫、猪疥螨、猪间虫体传染、猪肺蠕虫、猪虱及沙皮犬的蠕形螨病等寄生虫病的治疗效果较明显。
1. Insecticidal mechanism of doxacin
It mainly causes the opening of chloride channel controlled by glutamic acid in insect body, and the chloride ion also causes the supermation of nerve resting potential, which leads to paralysis and death caused by the obstruction of nerve conduction in insect body. In recent years, it has been found that doxacin has the characteristics of broad spectrum, high efficiency, low toxicity and safety, and has a good preventive and therapeutic effect on parasites (nematodes) and extracorporeal parasites (arthropods) in animals. It is also used for the prevention and control of many kinds of gastrointestinal and lung nematodes, such as cattle, sheep, horses, pigs, dogs, camels and so on.
2. Comparison with other antiparasite drugs
Compared with other ivermectin products sold in the market, doxacin has a wide range of antiparasites, high blood concentration in vivo, slow elimination (doxacin half-life 5.7 days, ivermectin half-life 4.2 days), long duration of efficacy, no allergic reaction and other characteristics, so it is a good substitute for ivermectin. It is also the best effective and most potential new animal antiparasite drug in the world.
[project advantage]
[technical index] (Streptomyces avermefaciens) fermentation cycle 15 days, fermentation level 2000 ≤ 2600u / ml, yield 50 ≤ 55%
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
24, Milbethromycin
Feed [technical field]
[summary of the project] Milbemycin (also known as Mibaimycin,) (milbemycins)) is a microbial with a mixture of hexadecyllides isolated from Streptomyces hygroscopicussugsp, aureolacrimosus fermentation broth. Milbemycin has a high control effect on all kinds of mites. Most of the 20 components of the natural product have broad-spectrum control activity against agricultural pests, such as aphids, mites, caterpillars, intestinal parasites and other parasites that harm crops and livestock. The drug has strong effect on pests, less dosage, safe to people and animals, no pollution to the environment, only killing pests, not harming natural enemies, and is not easy to produce resistance. It can be used as a compound and rotating drug to prevent the resistance of this kind of drugs. At present, it is the most promising broad-spectrum, efficient and non-cross-resistant biological insecticide. Some experts predict that it can replace organophosphorus, carbamate, pyrethroid and organochlorine compounds currently used in crop protection. The main producers are Japan and Novartis in the United States.
[project advantage]
[technical index] (Streptomyces hygroscopum mutant) fermentation cycle 12 ≤ 15 days, fermentation level 1200 ≤ 2200 U / ml, extraction 65%, synthesis 50 ≤ 55%, overall yield more than 30%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
25, Virgiriamicin.
Feed [technical field]
[summary of the project] Viginimycin is an antibiotic extracted from Streptomyces by the Skee Pharmaceutical Factory Animal and Peasant Health Company in the United States. It consists of a mixture of 70%M1 and 30%S1. M1 is macrocyclic lactone and S1 is cyclic polypeptide. The structure of the two is different, and the antibacterial range is also different. S1 and M1 were mixed to improve antibacterial activity and no drug resistance. It only has inhibitory effect on Gram-positive bacteria. Its main effect is to inhibit the ribosomal (Ribosome), of bacteria and prevent the synthesis of bacterial proteins to achieve bactericidal effect.
 
Virginia is hardly absorbed in the intestinal tract of livestock and poultry, and the residue in livestock and poultry tissues is very little after treatment. The additive can prevent and cure bacterial dysentery and chicken necrotizing enteritis. It kills harmful and redundant intestinal bacteria, reduces the production of lactic acid, ammonia, volatile fatty acids and other toxic substances, thus slowing down intestinal peristalsis, prolonging the retention time of feed in the intestinal tract, and increasing the absorption of nutrients. As an antibiotic, it makes the small intestinal wall thinner and increases the permeability of the intestinal wall, which can promote the absorption and utilization of amino acids and phosphorus, improve the feed utilization rate and promote the growth. It can also increase the absorption of yellow pigment in feed and the content of yellow pigment in chicken and egg. Its quality is characterized by good stability, keeping the titer unchanged for three years at room temperature, and its particles are small, about 500000 particles per gram, which is beneficial to uniform distribution in feed.
 
Virginia is a streptozotoxin antibiotic fermented by Streptomyces olivary (Streptomyces olivaceus).
[project advantage]
[technical index] (Streptomyces olive) fermentation cycle 144 ±12 h, fermentation level 0.6 ±0.2 g ·L, yield ≥ 55%
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
 
 
26, serine (30 liter small pot technology) 90 h, 25g/L above 17% 60%
Feed [technical field]
[project overview]
[project advantage]
[technical indicators]
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
27, Numokangding B0capfen net precursor,
Feed [technical field]
[project overview]
[project advantage]
[technical index] fermentation unit: 2 ≤ 3 g / L, fermentation time: 15 days, extraction yield: 45%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
28, acanthocin B
Feed [technical field]
[project overview]
[project advantage]
[technical index] Anifen net precursor, fermentation unit: 2000 mg ·L, fermentation time: 6 × 7 days, product yield: 45%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
29 vanillin
Food [technical field]
Natural vanillin is a white needle crystal with strong milk aroma and is widely used in candy, meat processing, pastries, milk, ice cream, juice drinks, tea drinks, alcoholic drinks, sauces and sauces. It is used as a changing agent, a fixing agent and a mixer in the flavor formula. He has the reputation of "King of spices". The production of natural vanillin by fermentation is a kind of biotransformation, which has advantages over any other method. This method is not affected by the specific climate and environment, the condition is mild, belongs to the non-labor-intensive process, the production process does not contain toxic and harmful substances, not only improves the safety factor of production and reduces the pressure of environmental pollution, the price of raw materials is relatively low and the product output is high, the quality is in accordance with the natural standards, and can replace the vanillin obtained from natural extraction.
[project advantage]
[technical index] fermentation cycle: 40 hours, fermentation unit: 8.5g/L
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
Thirty, lasporin.
Feed [technical field]
[summary of the project] Lacharithromycin is an anti-coccidiosis antibiotic developed by Roche in 1951. Obtained by fermentation and culture of streptomycin in Lachary, it is white to brown powder, slightly soluble in water and soluble in most organic solvents. The stability is high. It can be preserved at 37 ℃ for 6 months, and the content of the premixture can be preserved at 25 ℃ for 12 months, and the content of the premixture is still above 95%.
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
Lacharixin has affinity to divalent metal ions and has good anti-coccidiosis effect. Since 1979, the United States has approved it as an anti-coccidiosis agent, using its sodium salt, sodium lasporin.
 
In recent years, the United States has listed sodium lasarisin as a growth promoter for beef cattle, known as Bovatec.. It is said that it is superior to rumen in increasing daily weight gain and feed conversion rate, and is safe for horses. Unlike the use of rumen, 20% of cattle in concentrate beef cattle develop liver abscess, so their use tends to increase.
[project advantage]
[technical index] fermentation unit 20 ≤ 30 g ·L, extraction yield 60 ≤ 70%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
31, β-alanine
Feed [technical field]
[summary of the project] β-alanine (Beta- alanine), that is, 3-aminopropionic acid, β-alanine, is a kind of multi-purpose organic raw material, which can be used in the synthesis of pantoic acid and calcium pantothenate, carnosine, sodium pamironate, baluitine and so on. It is widely used in medicine, feed, food and other fields. β-alanine is still in a period of development in China. The product is mainly used for the synthesis of calcium pantothenate. The production technology of β-alanine has always been an important scientific research topic in China, but it is difficult to improve for various reasons, which greatly limits the development and application of downstream products, especially calcium pantothenate.
 
In recent years, due to the rapid development of downstream products synthesized from β-alanine, especially the wide application of β-alanine in food and medicine, the demand for β-alanine in domestic and foreign markets continues to grow, the market demand for β-alanine expands rapidly, the contradiction between supply and demand is very prominent, and the gap between supply and demand is large, so the prospect of β-alanine development and production is very broad.
[project advantage]
[technical index] fermentation cycle: 24 × 30 h, fermentation cell wet weight: 100Kg/t fermentation broth, biotransformation dosage: 30-50Kg/t conversion solution, L-aspartic acid concentration: 130 × 150 g ·L, conversion time: 15? 20 h, final product concentration: 80? 90 g / L, molar conversion more than 90%
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
32, L-Leucine
Feed [technical field]
[summary of the project] Leucine, isoleucine and valine are branch chain amino acids that help promote muscle recovery after training. Leucine is the most effective branch chain amino acid, which can effectively prevent muscle loss because it can decompose and convert into glucose more quickly. Increasing glucose prevents damage to muscle tissue, so it is especially suitable for bodybuilders. Leukine also promotes healing of bones, skin, and damaged muscle tissue, and doctors usually advise patients to take Leucine supplements after surgery.
Because it is easy to convert to glucose, Leucine helps regulate blood sugar levels. People with leukine deficiency have symptoms similar to hypoglycemia, such as headache, dizziness, fatigue, depression, mental disorder, and irritability.
[project advantage]
[technical index] A Leucine producing strain was obtained by genetic modification and strain breeding. The main technical index was acid production 60g ±10g / L, conversion rate 20 ±2%, cycle 50 ±2h.
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
 
33, dialcohol (4BNA)
Medicine [in the field of technology]
[summary of the project] steroid hormone intermediate, CAS:60966-36-1, is the intermediate of progesterone synthesis. Ursolic acid or shark polyamines with higher added value can also be developed.
[project advantage]
 
[technical index] Mycobacterium aureus, substrate phytosterol, 30 g ·L ~ (- 1), conversion rate 40 ~ 50%, main excipients Tween, hydroxypropyl cyclodextrin, oil-free process, 4BNA concentration 13.5 g / L, fermentation (transformation) cycle 6 days.
 
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
33, stosporin
Medicine [in the field of technology]
[summary of the project] Staurosporine,STS is a class of indole alkaloids, which is a protein kinase C (Proteinkinase C inhibitor, which can induce cell death and has antitumor activity and anticancer effect. Stosporin was first isolated from mold staurosporeus in 1977 and later found and expressed in marine microorganisms. At present, many people at home and abroad have begun to study the fermentation process of stosporin, but the fermentation cost is relatively high.
[project advantage].
[technical index] the fermentation cycle is 7 days, the shaking flask is 600ug / ml, and the highest is 800 ug/ml,.
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
34, L-histidine
Medicine [in the field of technology]
[summary of the project] the chemical name of L-histidine (L-Histidine) is L-α-amino-β-imidazolinic acid, which is an basic amino acid containing imidazolium nucleus in molecules. L-histidine has many physiological functions and is widely used in medicine, feed and food industry. Especially in the field of medicine, more and more attention has been paid to its role. At present, it is mainly used in amino acid infusion and comprehensive amino acid preparation. It has become one of the most commonly used drugs in Chinese medical treatment, and the dosage is increasing year by year. However, at present, the advanced technology of L-histidine production is mainly in the hands of Europe, the United States, Japan and other developed countries, mainly using fermentation method.
[project advantage] the fermentation conditions of L-histidine were optimized by neural network, pattern recognition, genetic algorithm and other optimization methods. According to the principle of metabolic engineering, the metabolic network of L-histidine biosynthesis was constructed, on the basis of which the pathway analysis and metabolic flow analysis of L-histidine biosynthesis network were carried out. Microfiltration, ultrafiltration, nanofiltration and other membrane filtration processes were used to remove bacterial protein, pigment and salt, and then histidine was separated and extracted.
[technical index] fermentation cycle: 68 ≤ 76 hours, acid production 25 ≤ 30 g ·L, sugar and acid conversion 8 ≤ 10%
 
[expected benefits]
[status of awards and patents]
[technological maturity] production scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
35, β-mannanase
Feed [technical field]
[summary of the project] β-mannanase is one of the most important dietary enzyme preparations, and it is the most effective dietary enzyme preparation for corn / soybean meal diet. the digestive enzymes of livestock, poultry and fish do not contain mannanase. The addition of β-mannanase mainly can promote animal growth, improve animal feed conversion efficiency, promote nutrition digestion, improve animal intestinal microbial ecology, improve animal health, reduce intestinal content viscosity, reduce fecal excretion, reduce environmental pollution, and improve the bioavailability of trace elements.
 
Strain: Pichia pastoris engineering strain, which is a high copy genetically engineering strain screened by G418 after secondary transformation on the basis of the strain used in production. Compared with the previous strains, the strains have the characteristics of fast growth, high enzyme activity and high enzyme production rate.
 
30L test results:
After three batches of small-scale experiments, the results showed that the enzyme production ability of the strain was stable, and the highest enzyme activity was close to 5000 U ·mL at 30 h, while the highest enzyme activity reached 1500 U/mL at about 120 h.
There are the following reasons for such a great change in the enzyme production performance of the strain:
Strain 1. The strain is a high copy engineering strain screened out.
(2) the shaking flask experiment was carried out by SAS software on the basis of the original traditional BSM medium, and the composition and concentration of the medium were changed greatly, which was more suitable for the growth and enzyme production of the strain.
(3) the process improvement improved the feeding and methanol induction strategy in the fermentation process.
 
At present, the project is only a laboratory pilot stage, but also need to carry out pilot-scale amplification. Through shaking flask experiment and 30L fermentation results, we can see that the enzyme production capacity is stable after amplification, and I believe it can be realized by pilot-scale amplification.
 
Rough calculation of costs:
According to 60T fermenter and feeding 20T, the cost of culture medium is about 8000 yuan, the energy consumption is 6600 yuan per hour, the total amount of methanol and glycerol is about 30000 yuan, and the total cost is about 44000 yuan.
[project advantage] the product has a large market in the feed enzyme preparation industry. in the production process, the project has the characteristics of short fermentation cycle, low cost and high enzyme production rate, so once it is introduced in the market, it is believed to have great market advantages.
[technical index] the highest enzyme activity reached nearly 5000 U ·mL at 30 h, while the highest level of enzyme activity reached 1500 U/mL at about 120 h.
 
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
36, galactosidase
Feed [technical field]
[project overview]
Project background: α-galactoside is an oligosaccharide composed of one or two galactose linked by a sucrose unit with α-1 and 6 glycosides. It mainly includes cottonseed sugar, stachyose and furfurose, which are widely found in various plants, most of which are leguminous plants. The contents of α-galactose in soybean were 1.4% and 5.2%, respectively, and the content of α-galactose in cottonseed meal was 3.6%. α-galactose glycosides have good thermal stability and will not decompose even at high temperatures. Soybean has the nutritional characteristics of high crude protein content, rich in lysine and other amino acids, but many anti-nutritional factors reduce its feeding value. The anti-nutritional effect of α-galactose glycosides was first found in the field of human nutrition research, also known as "flatulence factor". After some galactoside substances entered the large intestine, they were transformed into volatile fatty acids due to E. coli fermentation, resulting in CO2,H2 and a small amount of CH4 gas, resulting in flatulence, vomiting, dysentery and other phenomena, at the same time, it also reduced the digestive energy value of α-galactoside raw materials.
α-galactosidase is an enzyme that catalyzes the decomposition of α-galactoside to obtain monosaccharide such as oligosaccharide and fructose. As a specific exogenous enzyme, the addition of α-galactosidase to feed containing soybean meal can effectively promote the decomposition of α-galactosidase in meal feed, improve feed utilization rate and eliminate the anti-nutritional effect caused by α-galactoside. At present, a large number of research results show that adding α-galactosidase to monogastric animal feed can not only degrade insoluble oligosaccharide and improve the metabolic energy of soybean meal, but also eliminate flatulence in intestinal tract and increase animal feed intake.
 
Strain: constructed Pichia pastoris genetic engineering strain containing galactoside gene
 
The results of 50L small scale test: after three batches of fermentation experiment, the highest enzyme activity reached 200u/mL in about 200h.
 
This product is a new product, at present, the market is still relatively small, and the enzyme activity is low, the enzyme activity is about 100 u ≤ mL, so the project has great market potential.
 
Further research is needed: in the process of small-scale trial, fermentation is carried out entirely according to the Biki genetic engineering culture method of other enzymes, including culture medium and fermentation process. Because the foreign genes carried by the engineering bacteria are different, the growth and induced enzyme production strategy of the strain will also be different, so the culture medium and fermentation conditions need to be further studied to find the culture medium and fermentation process suitable for the growth and enzyme production of the strain. It is hoped that further research can shorten the fermentation cycle and reduce the cost. I believe that there is still a lot of room for improvement in the unit enzyme activity of fermentation broth, and the amplification process can be realized in the pilot test.
[project advantage] this product is a new product, at present, the market is still relatively small, and the enzyme activity is low, the enzyme activity is about 100 u ≤ mL, so the project has great market potential.
[technical index] the highest enzyme activity reached 200u/mL in about 200 hours.
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
37, sirolimus (sirolimus), rapamicin (rapamycin)
Medicine [in the field of technology]
Sirolimus is a new macrolides immunosuppressant with high immunosuppressive effect, and its IC50 is 1% of cyclosporine A. The role of sirolimus in the cells of the body requires binding to the immune binding protein FK 506 (FK 506-Binding Proteins,FKBPs) to form a complex, binding to the Rapalnycin target of mammal cells (a key regulatory kinase of mTOR,) and inhibiting its activation [2] in order to exert its immunosuppressive effect.
It has been found that although there are some problems in the fermentation of sirolimus, such as low ability to produce sirolimus, long fermentation cycle, many intermediate products, inhibition of high concentration products and substrate, complex separation and extraction of fermentation broth, sirolimus has dozens of times more immunosuppressive activity than cyclosporine, which is widely used in clinical practice, while the toxicity of kidney is much lower and there is no neurotoxicity. In addition, some studies have shown that this kind of drug can also prolong the life span of invertebrates such as yeast, nematodes, fruit flies and so on. Therefore, sirolimus has a broad application prospect in the field of medicine.
[project advantage]
[technical index] rapamicin (Streptomyces hygroscopum mutant), fermentation cycle 160 × 200 h, fermentation level 1000 ±200mg/L extraction yield ≥ 30% (product purity ≥ 98%)
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
 
38, fermentation method for the production of amphotericin B strain and process
Medicine [in the field of technology]
[summary of the project] Amphotericin B (Amphotericin B) is a polyene antifungal antibiotic, which can inhibit the growth of fungi by affecting the permeability of cell membrane. Clinically used to treat visceral or systemic infections caused by severe deep fungi.
Streptomyces (S. Lushanensis), was used in the production of amphotericin B in liquid medium with soybean cake powder, glucose, dextrin, corn milk and phosphate as the main carbon, nitrogen and phosphorus sources. Amphotericin B was synthesized by three-stage fermentation at 27 ℃.
[project advantage]
[technical index] fermentation level: 10000U/ml (HPLC), fermentation cycle: 130 ≤ 140 hours, extraction yield: 70%
[expected benefits]
[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction
If you have any other questions, please feel free to contact the biotechnology Transfer Center at 01056205725; 13911873657; 18515624029; 13681366571 Zheng Wei email: 380721775@qq.com
39, ergosterol
Medicine [in the field of technology]
Ergosterol is an important chemical product and a precursor to the production of fat-soluble vitamin D2 and various sterols. Ergosterol is an important component of fungal cell membrane, which plays an important role in ensuring the integrity of membrane structure, ensuring the activity of membrane binding enzyme, membrane mobility, cell activity and material transport. At present, there are two main methods to produce ergosterol in China: one is to extract ergosterol from the remaining waste filaments of penicillin and citric acid produced by fermentation industry. Second, the production of ergosterol producing strain was carried out by breeding and fermentation of ergosterol producing strain.
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[status of awards and patents]
[technology maturity] pilot scale
Technology transfer [through cooperation]
[photo of results] A brief introduction