CN103233052B - Composite organic nitrogen source for erythromycin fermentation - Google Patents
Composite organic nitrogen source for erythromycin fermentation Download PDFInfo
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- CN103233052B CN103233052B CN201310124801.4A CN201310124801A CN103233052B CN 103233052 B CN103233052 B CN 103233052B CN 201310124801 A CN201310124801 A CN 201310124801A CN 103233052 B CN103233052 B CN 103233052B
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Abstract
A composite organic nitrogen source for erythromycin fermentation and a culture medium. The organic nitrogen source is prepared by mixing soybean meal, cottonseed meal, peanut meal, corn steep liquor powder and corn gluten meal, and the resulting mixture is the composite organic nitrogen source. According to the composite organic nitrogen source provided by the present invention, because on the basis of ensuring the balance of total nitrogen, contents of a variety of amino acids are adequately cooperated, especially the contents of methionine, valine, leucine and iso-leucine which play important roles in the erythromycin fermentation process, an erythromycin fermentation level can be effectively increased, fermentation ingredients are improved, the cost of nitrogen source for fermentation is also greatly reduced, and good economic benefits are provided.
Description
Technical field
The invention belongs to field of fermentation engineering, be specifically related to a kind of for the sugared many born of the same parents bacterium of redness (
saccharopolyspora erythraea) fermentation compound organic nitrogen source.
Background technology
Erythromycin (Erythromycin) be by the red sugared many born of the same parents bacterium of streptomyces (
saccharopolyapora erythraea) a kind of 14-membered ring macrolides microbiotic of producing, thering is broad-spectrum antibacterial action, its mechanism of action is to combine with the 50S subunit of bacterial ribosome albumen, the activity of inhibiting peptide acyltransferase, thus anti-bacteria protein is synthetic.Along with Azythromycin, the market of the novel semi-synthetic erythromycin such as clarithromycin constantly expands, and the production and selling of erythromycin bulk drug is increasingly active.
Soybean cake powder is organic nitrogen source conventional in Fermentation Industry, especially in Erythromycin Fermentation Process, playing the part of important role, not only in early stage, can be used as the carbon skeleton of thalli growth, and provide required amino acid for the thalline of middle and later periods maintains and produce element.In soybean protein, amino acid whose composition is relatively abundant, but in soybean, the content of methionine(Met), α-amino-isovaleric acid, leucine and Isoleucine compares less, yet these several seed amino acids play an important role in Erythromycin Fermentation Process, (methionine(Met), as the precursor of methyl donor S-adenosylmethionine, plays positive promoter action to the rear modification of erythromycin; α-amino-isovaleric acid, leucine and Isoleucine are the main amino acid in propionyl coenzyme A precursor source).Existing bibliographical information, really can produce active influence to the fermenting process of erythromycin adding suitable amino acid in substratum or in fermenting process, but be really applied to the few of industrialized production, the high price of amino acid can increase the material cost of fermenting process greatly after all, and a lot of experiments have also only rested on laboratory stage.
Summary of the invention
For the deficiencies in the prior art, the object of this invention is to provide a kind of compound organic nitrogen source for abomacetin fermentation, be beneficial to improve fermentation level, improve fermentation component and reduce raw materials cost.
The object of the present invention is achieved like this: a kind of compound organic nitrogen source for abomacetin fermentation, described compound organic nitrogen source is mixed by soybean cake powder, cottonseed meal, groundnut meal, Dried Corn Steep Liquor Powder and Zein powder, the mixture obtaining is compound organic nitrogen source, in weight part: soybean cake powder 38-42, cottonseed meal 9-11, groundnut meal 9-11, Dried Corn Steep Liquor Powder 18-22, Zein powder 18-22, the aminoacids content in the organic nitrogen source obtaining is as follows:
Aspartic acid 1.74-5.15%, Threonine 1.72-2.19%, Serine 1.56-2.25%, L-glutamic acid 5.25-8.01%, glycine 0.63-1.88%, L-Ala 1.88-2.12%, methionine(Met) 0.60-1.31%, α-amino-isovaleric acid 2.27-3.81%, Isoleucine 2.14-2.38%, leucine 3.50-5.44%, tyrosine 1.33-5.36%, phenylalanine 2.36-5.62%, Methionin 1.25-2.78%, arginine 1.88-3.18%, Histidine 1.20-2.13%, proline(Pro) 2.32-6.62%.
In described organic nitrogen source, aminoacids content is as follows: aspartic acid 2.84-4.81%, Threonine 1.93-1.98%, Serine 1.87-2.05%, L-glutamic acid 6.34-7.08%, glycine 0.95-1.57%, L-Ala 1.97-2.05%, methionine(Met) 0.70-1.09%, α-amino-isovaleric acid 2.85-3.11%, Isoleucine 2.19-2.21%, leucine 3.91-4.84%, tyrosine 2.78-4.15%, phenylalanine-3,4-quinone .15-4.85%, Methionin 1.42-2.12%, arginase 12 .18-2.97%, Histidine 1.70-2.03%, proline 3 .86-4.89%.
In described mixing, in weight part: soybean cake powder 40, cottonseed meal 10, groundnut meal 10, Dried Corn Steep Liquor Powder 20, Zein powder 20.
A fermention medium that utilizes above-mentioned compound organic nitrogen source to make, described fermention medium is composed as follows: starch 3.5-4.0%, compound organic nitrogen source 4.0-4.5%, ammonium sulfate 0.1-0.3%, soya-bean oil 0.2-0.6%, calcium carbonate 0.1-0.5%, defoamer 0.01-0.02%, surplus are water.
Compound organic nitrogen source for abomacetin fermentation provided by the invention, made up the deficiency of some aminoacids content in soybean cake powder, avoid again adding the cost increase that amino acid causes, by each raw material amino acid form and content is analyzed, obtained the compound organic nitrogen source of applicable abomacetin fermentation.
Compound organic nitrogen source provided by the invention, content due to the methionine(Met), α-amino-isovaleric acid, leucine and the Isoleucine that especially play an important role in Erythromycin Fermentation Process at the various amino acid whose content that guarantees fully to have arranged in pairs or groups on the basis of total nitrogen balance, can effectively improve abomacetin fermentation level, improve fermentation component, also greatly reduce fermentation nitrogen source cost, there is good economic benefit simultaneously.
Embodiment
Embodiment 1: get soybean cake powder 38-42Kg, and cottonseed meal 9-11 Kg, groundnut meal 9-11 Kg, Dried Corn Steep Liquor Powder 18-22 Kg, Zein powder 18-22 Kg is fully pulverized and mixed, and the aminoacids content in the organic nitrogen source obtaining is as follows:
Aspartic acid 1.74-5.15%, Threonine 1.72-2.19%, Serine 1.56-2.25%, L-glutamic acid 5.25-8.01%, glycine 0.63-1.88%, L-Ala 1.88-2.12%, methionine(Met) 0.60-1.31%, α-amino-isovaleric acid 2.27-3.81%, Isoleucine 2.14-2.38%, leucine 3.50-5.44%, tyrosine 1.33-5.36%, phenylalanine 2.36-5.62%, Methionin 1.25-2.78%, arginine 1.88-3.18%, Histidine 1.20-2.13%, proline(Pro) 2.32-6.62%.
Embodiment 2: soybean cake powder 40 Kg, and cottonseed meal 10 Kg, groundnut meal 10 Kg, Dried Corn Steep Liquor Powder 20 Kg, Zein powder 20 Kg are fully pulverized and mixed, and the aminoacids content in the organic nitrogen source obtaining is as follows:
Aspartic acid 2.84-4.81%, Threonine 1.93-1.98%, Serine 1.87-2.05%, L-glutamic acid 6.34-7.08%, glycine 0.95-1.57%, L-Ala 1.97-2.05%, methionine(Met) 0.70-1.09%, α-amino-isovaleric acid 2.85-3.11%, Isoleucine 2.19-2.21%, leucine 3.91-4.84%, tyrosine 2.78-4.15%, phenylalanine-3,4-quinone .15-4.85%, Methionin 1.42-2.12%, arginase 12 .18-2.97%, Histidine 1.70-2.03%, proline 3 .86-4.89%.
?compound organic nitrogen source is used for abomacetin fermentation:
One, cultural method and parameter detection method
Bacterial classification: red sugared many born of the same parents bacterium Q8(Saccharopolyapora erythraea Q8)
Substratum: fermention medium: starch 3.5-4.0%, compound organic nitrogen source 4.0-4.5%, ammonium sulfate 0.1-0.3%, soya-bean oil 0.2-0.6%, calcium carbonate 0.1-0.5%, bubble enemy 0.01-0.02%, water 90.20-91.60%.
Control formula: starch 3.5-4.0%, soybean cake powder 4.0-4.5%, ammonium sulfate 0.1-0.3%, soya-bean oil 0.2-0.6%, calcium carbonate 0.1-0.5%, bubble enemy 0.01-0.02%, water 90.20-91.60%.
Cultural method: adopt three grade fermemtation mode, taking fresh inclined-plane (1cm * 1cm) is inoculated in the 500mL seed shaking flask that 50mL substratum is housed, after the lower 34 ℃ of cultivation 40h of 220r/min rotating speed, proceed to 15L seeding tank, process maintains dissolved oxygen more than 40%, cultivate 40h for 34 ℃ and move into 50L fermentor tank, 34 ℃ of online 185h that cultivate, process maintains dissolved oxygen more than 30%.
Parameter detection method: chemical titer: sulphuric acid hydrolysis.
Erythromycin Components in fermented liquid: adopt HPLC analytical method, Waters Xbridge C18 chromatographic column (4.6mm * 250mm, 5 μ m, Waters Corporation).Moving phase 0.025mol/L potassium dihydrogen phosphate: acetonitrile=60:40, flow velocity 1ml/min, 35 ℃ of column temperatures, detect wavelength 215nm, sample size 20 μ l.
Experimental result: applicant, to the fermented liquid component before and after nitrogenous source adjustment is measured and analyzed, the results are shown in Table 1.Compare photograph, active principle EryA has improved 3.3%, and impurity composition EryB, EryC have declined respectively 29.2% and 29.4%.
The variation of abomacetin fermentation component after table 1 optimization nitrogenous source
The compound nitrogen source of the present invention's design derives from large agricultural byproducts, and low price, steady quality, wide material sources, can be applied to plant-scale production completely.This compound nitrogen source is not only applicable to erythromycin and produces, and the production of antibiotics of other Macrolidees is also had to certain operability.
Claims (3)
1. a fermention medium that adopts compound organic nitrogen source to make, is characterized in that: described fermention medium is composed as follows: starch 3.5-4.0%, compound organic nitrogen source 4.0-4.5%, ammonium sulfate 0.1-0.3%, soya-bean oil 0.2-0.6%, calcium carbonate 0.1-0.5%, defoamer 0.01-0.02%, surplus are water;
Described compound organic nitrogen source is fully pulverized and mixed and forms by soybean cake powder, cottonseed meal, groundnut meal, Dried Corn Steep Liquor Powder and Zein powder, the mixture obtaining is compound organic nitrogen source, in weight part: soybean cake powder 38-42, cottonseed meal 9-11, groundnut meal 9-11, Dried Corn Steep Liquor Powder 18-22, Zein powder 18-22, the aminoacids content in the organic nitrogen source obtaining is as follows:
Aspartic acid 1.74-5.15%, Threonine 1.72-2.19%, Serine 1.56-2.25%, L-glutamic acid 5.25-8.01%, glycine 0.63-1.88%, L-Ala 1.88-2.12%, methionine(Met) 0.60-1.31%, α-amino-isovaleric acid 2.27-3.81%, Isoleucine 2.14-2.38%, leucine 3.50-5.44%, tyrosine 1.33-5.36%, phenylalanine 2.36-5.62%, Methionin 1.25-2.78%, arginine 1.88-3.18%, Histidine 1.20-2.13%, proline(Pro) 2.32-6.62%.
2. the fermention medium that employing compound organic nitrogen source according to claim 1 is made, it is characterized in that: in described organic nitrogen source, aminoacids content is as follows: aspartic acid 2.84-4.81%, Threonine 1.93-1.98%, Serine 1.87-2.05%, L-glutamic acid 6.34-7.08%, glycine 0.95-1.57%, L-Ala 1.97-2.05%, methionine(Met) 0.70-1.09%, α-amino-isovaleric acid 2.85-3.11%, Isoleucine 2.19-2.21%, leucine 3.91-4.84%, tyrosine 2.78-4.15%, phenylalanine-3,4-quinone .15-4.85%, Methionin 1.42-2.12%, arginase 12 .18-2.97%, Histidine 1.70-2.03%, proline 3 .86-4.89%.
3. the fermention medium that employing compound organic nitrogen source according to claim 1 is made, is characterized in that: in described mixture, in weight part: soybean cake powder 40, cottonseed meal 10, groundnut meal 10, Dried Corn Steep Liquor Powder 20, Zein powder 20.
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| CN105462837A (en) * | 2015-12-31 | 2016-04-06 | 青岛海科生物技术有限公司 | Composite organic nitrogen source and preparation method thereof |
| CN108467879B (en) * | 2017-02-23 | 2021-07-30 | 华东理工大学 | Synthetic medium for erythromycin fermentation |
| CN106916770A (en) * | 2017-04-20 | 2017-07-04 | 王晓雨 | Compound organic nitrogen source kit |
| CN114854805A (en) * | 2022-05-30 | 2022-08-05 | 山东胜利生物工程有限公司 | Hainanmycin fermentation medium and fermentation method |
Citations (4)
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|---|---|---|---|---|
| JPH05286990A (en) * | 1992-04-08 | 1993-11-02 | Meiji Seika Kaisha Ltd | New macrolide antibiotic and production of macrolide antibiotic utilizing conversion of microorganism |
| CN101225404A (en) * | 2008-01-25 | 2008-07-23 | 华东理工大学 | Compound organic nitrogen source used for microbial fermentation |
| CN102409071A (en) * | 2011-12-02 | 2012-04-11 | 伊犁川宁生物技术有限公司 | Fermentation method of erythromycin fermentation liquid |
| CN102757991A (en) * | 2012-07-17 | 2012-10-31 | 宁夏泰瑞制药股份有限公司 | Method for improving erythromycin fermentation titer and promoting erythromycin A synthesis |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05286990A (en) * | 1992-04-08 | 1993-11-02 | Meiji Seika Kaisha Ltd | New macrolide antibiotic and production of macrolide antibiotic utilizing conversion of microorganism |
| CN101225404A (en) * | 2008-01-25 | 2008-07-23 | 华东理工大学 | Compound organic nitrogen source used for microbial fermentation |
| CN102409071A (en) * | 2011-12-02 | 2012-04-11 | 伊犁川宁生物技术有限公司 | Fermentation method of erythromycin fermentation liquid |
| CN102757991A (en) * | 2012-07-17 | 2012-10-31 | 宁夏泰瑞制药股份有限公司 | Method for improving erythromycin fermentation titer and promoting erythromycin A synthesis |
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