CN105296571A - Method for increasing erythromycin fermentation titer - Google Patents
Method for increasing erythromycin fermentation titer Download PDFInfo
- Publication number
- CN105296571A CN105296571A CN201510797249.4A CN201510797249A CN105296571A CN 105296571 A CN105296571 A CN 105296571A CN 201510797249 A CN201510797249 A CN 201510797249A CN 105296571 A CN105296571 A CN 105296571A
- Authority
- CN
- China
- Prior art keywords
- fermentation
- erythromycin
- ammoniumsulphate soln
- tired
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention relates to a method for increasing erythromycin fermentation titer. The method is characterized in that during a process for fermentation production of erythromycin by taking Saccharopolyspora erythraea as an original strain, an ammonium sulfate solution is slowly added. According to the invention, the ammonium sulfate solution is fed after fermentation is carried out for 60 hours, due to massive breeding of mycelia at this period, large utilization of a nitrogen source of a base material is carried out, oxygen demand of a broth is large, broth viscosity is large, volume is increased, by slowly feeding the ammonium sulfate solution, broth viscosity is changed, dissolved oxygen is improved, synthesis of components of erythromycin can be adjusted, nitrogen source supplement can be simultaneously carried out, thalline vitality is increased, an erythromycin secretion period is prolonged, and an erythromycin fermentation level can be increased.
Description
Technical field
The present invention relates to field of microbial fermentation, particularly relate to a kind of method improving abomacetin fermentation and tire.
Background technology
Erythromycin is macrolide antibiotics, and antimicrobial spectrum is similar to penicillin, is usually used in the treatment to penicillin anaphylaxis person clinically.In recent years because the extensive exploitation of erythromycin derivatives uses, the demand of erythromycin is constantly increased.
In prior art, set out in the process of strain fermentation production erythromycin with the sugared many born of the same parents bacterium of redness, whole process fills into containing imitating in a large number nitrogenous source, the mixed nitrogen of phosphoric and syrup late, this method has following technical disadvantages: 1) along with mycelium amount reproduction, middle and later periods volume increases, and causes the shortage of dissolved oxygen; 2) slow owing to imitating nitrogenous source consumption late, fermentation ends is residual comparatively large, the effect that impact is extracted and final product quality; 3) some bacterial classification is omnidistance only need fill into syrup, in basestocks, only adds the nitrogenous source of q.s, early stage can be caused so nutritious, mycelia amount reproduction, nitrogenous source consumption is large, and fermentation broth viscosity, fermented liquid surface tension strengthen, and the transfer efficiency of oxygen reduces, dissolved oxygen concentration reduces, cause thalline dissolved oxygen to lack, middle and later periods nitrogenous source lacks, and mycelia is old and feeble in advance, fermentation period shortens, decreased yields.
Summary of the invention
The object of the invention is to the defect overcoming above-mentioned prior art, a kind of method that effective raising erythromycin is tired is provided.
Technical scheme taked for achieving the above object is:
Improve the method that abomacetin fermentation is tired, it is characterized in that: produce in the process of erythromycin at the strain fermentation that sets out with the sugared many born of the same parents bacterium of redness, slow stream adds and fills into ammoniumsulphate soln.
The amount of filling into of described ammoniumsulphate soln adds up to the 5-10% of fermentating liquid volume.
Described ammoniumsulphate soln mass body volume concentrations is 2-5%.
Described ammoniumsulphate soln mass body volume concentrations is 2-3%.
Constantly little to 60 in fermentation, start slow stream and add ammoniumsulphate soln.
Ammoniumsulphate soln is added at fermentation 80-140 hour slow stream.
The present invention is by adding ammoniumsulphate soln at the little stream that starts constantly of fermentation 60, and due to mycelia amount reproduction in this, basestocks nitrogenous source utilizes more in period, fermented liquid oxygen requirement is large, and fermentation broth viscosity is large, and volume increases, ammoniumsulphate soln is added by slow stream, change fermentation broth viscosity, improve dissolved oxygen, regulate the synthesis of each component of erythromycin, nitrogenous source can be supplemented simultaneously, increase thalline vigor, extend the erythromycin secretory phase, thus improve abomacetin fermentation level.
Embodiment
The present invention is described in further detail by following examples; but the present embodiment the technology contents that describes be illustrative; instead of it is determinate; protection scope of the present invention should do not limited to according to this; within the spirit and principles in the present invention all; any amendment of doing, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
In following embodiment
Test tank whole process can detect the parameters such as dissolved oxygen, PH, temperature, mixing speed.
The stream dosage of ammonium sulfate is determined according to detection viscosity and dissolved oxygen situation.
Other feed supplement controls to carry out by normal process.
Preparation method: adopt three grade fermemtation to produce erythromycin, concrete steps are as follows:
1, slant pore preparation: be aseptically inoculated on solid medium by sugared for redness many born of the same parents bacterium, 35 DEG C of constant temperature culture 6-8 days, are inoculated in primary-seed medium.
2, above-mentioned slant pore substratum is conventionally prepared, and filling a prescription is: starch 8g/L, ammonium sulfate 2.5g/L, sodium-chlor 2.3g/L, calcium carbonate 2.4g/L, corn steep liquor 1.0g/L.
3, first order seed is cultivated: slant pore sterile manner step 1 grown is inoculated in primary-seed medium, 35 DEG C of constant temperature culture, and ventilation ratio is 1.5-2.0v/v/min, and mixing speed is 400-600r/min, cultivates 40-60 hour.
4, prepared by above-mentioned primary-seed medium ordinary method, and its formula is starch 100g/L, dextrin 50g/L, bean powder 75g/L, corn steep liquor 40g/L, ammonium sulfate 18g/L, sodium-chlor 15g/L, calcium carbonate 35g/L, soya-bean oil 20g/L.
5, secondary seed is cultivated: first order seed nutrient solution sterile manner step 3 grown is inoculated in secondary seed medium, 35 DEG C of constant temperature culture, and ventilation ratio is 1.5-2.0v/v/min, and mixing speed is 400-600r/min, cultivates 22-35 hour.
6, prepared by above-mentioned secondary seed medium ordinary method, and its formula is starch 300g/L, dextrin 200g/L, bean powder 350g/L, corn steep liquor 120g/L, ammonium sulfate 20g/L, sodium-chlor 25g/L, calcium carbonate 50g/L, soya-bean oil 30g/L.
7, fermentation culture: cultured for step 5 secondary seed aseptic condition is inoculated in respectively in embodiment and reference examples fermention medium, inoculum size is 10-20%, controls culture temperature 32-35 DEG C, process ventilation ratio: 0.8-1.5v/min, guarantee process dissolved oxygen is not less than 20%, cultivates 6-8 days.
8, prepared by fermention medium ordinary method.
Reference examples culture medium prescription is: starch 580g/L, dextrin 150g/L, bean powder 525g/L, corn steep liquor 300g/L, ammonium sulfate 40g/L, sodium-chlor 37.5g/L, calcium carbonate 105g/L, soya-bean oil 50g/L.
Embodiment fermentative medium formula: starch 580g/L, dextrin 150g/L, bean powder 375g/L, corn steep liquor 125g/L, ammonium sulfate 40g/L, sodium-chlor 37.5g/L, calcium carbonate 105g/L, soya-bean oil 45g/L.
Embodiment 1
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 60 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 3-5%, stream dosage per hour is controlled at 120-250L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-8% of fermentating liquid volume.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 175 hours, stop fermentation.
Embodiment 2
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 60 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 6%, stream dosage per hour is controlled at 120-200L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-8% of fermentating liquid volume.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 175 hours, stop fermentation.
Embodiment 3
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 80 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 3.0%, stream dosage per hour is controlled at 120-200L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-6% of fermentating liquid volume.Within 176 hours, stop fermentation.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 176 hours, stop fermentation.
Embodiment 4
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 80 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 6%, stream dosage per hour is controlled at 120-200L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-6% of fermentating liquid volume.Within 172 hours, stop fermentation.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 172 hours, stop fermentation.
Embodiment 5
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 80 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 1%, stream dosage per hour is controlled at 200-300L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-8% of fermentating liquid volume.Within 172 hours, stop fermentation.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 172 hours, stop fermentation.
Embodiment 6
1, getting the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method is inoculated in the embodiment fermention medium of step 7 preparation, cultivate according to regular culture conditions, fermentation started slow stream by 90 hours and adds ammoniumsulphate soln, described ammoniumsulphate soln concentration is 4%, stream dosage per hour is controlled at 150-250L/hr according to viscosity and dissolved oxygen situation, stream adds to stopping in 140 hours, and accumulative stream dosage is the 5-6% of fermentating liquid volume.Within 170 hours, stop fermentation.
2, get the cultured secondary seed medium aseptic condition of step 5 in above-mentioned preparation method to be inoculated in the normal control example fermention medium of step 7 preparation, cultivate according to regular culture conditions, within 170 hours, stop fermentation.
Claims (6)
1. improve the method that abomacetin fermentation is tired, it is characterized in that: produce in the process of erythromycin at the strain fermentation that sets out with the sugared many born of the same parents bacterium of redness, slow stream adds and fills into ammoniumsulphate soln.
2. according to the method that raising abomacetin fermentation according to claim 1 is tired, it is characterized in that: the amount of filling into of described ammoniumsulphate soln adds up to the 5-10% of fermentating liquid volume.
3. according to the method that the raising abomacetin fermentation described in claim 1 or 2 is tired, it is characterized in that: described ammoniumsulphate soln mass body volume concentrations is 2-5%.
4. according to the method that raising abomacetin fermentation according to claim 3 is tired, it is characterized in that: described ammoniumsulphate soln mass body volume concentrations is 2-3%.
5. according to the method that raising abomacetin fermentation according to claim 1 is tired, it is characterized in that: constantly little to 60 in fermentation, start slow stream and add ammoniumsulphate soln.
6. according to the method that the raising abomacetin fermentation described in claim 1 or 5 is tired, it is characterized in that: add ammoniumsulphate soln at fermentation 80-140 hour slow stream.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510797249.4A CN105296571A (en) | 2015-11-19 | 2015-11-19 | Method for increasing erythromycin fermentation titer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510797249.4A CN105296571A (en) | 2015-11-19 | 2015-11-19 | Method for increasing erythromycin fermentation titer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105296571A true CN105296571A (en) | 2016-02-03 |
Family
ID=55194393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510797249.4A Pending CN105296571A (en) | 2015-11-19 | 2015-11-19 | Method for increasing erythromycin fermentation titer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105296571A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110452945A (en) * | 2018-05-07 | 2019-11-15 | 华东理工大学 | Utilize the novel method of S. erythraea fermentations production erythromycin |
| CN110747246A (en) * | 2019-11-29 | 2020-02-04 | 宁夏启元药业有限公司 | Method for improving erythromycin fermentation unit |
| CN112553132A (en) * | 2019-09-25 | 2021-03-26 | 华东理工大学 | Optimized fermentation method of SacC gene knockout saccharopolyspora erythraea |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101519637A (en) * | 2009-04-07 | 2009-09-02 | 华东理工大学 | Red Saccharopolyspora and method for producing erythromycin by fermenting Saccharopolyspora |
| CN102041288A (en) * | 2010-04-02 | 2011-05-04 | 华东理工大学 | Method for improving fermentation of erythromycin by adding dimethyl sulfoxide |
| CN102586366A (en) * | 2012-02-23 | 2012-07-18 | 安徽丰原发酵技术工程研究有限公司 | Method for producing erythrocin at high yield |
-
2015
- 2015-11-19 CN CN201510797249.4A patent/CN105296571A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101519637A (en) * | 2009-04-07 | 2009-09-02 | 华东理工大学 | Red Saccharopolyspora and method for producing erythromycin by fermenting Saccharopolyspora |
| CN102041288A (en) * | 2010-04-02 | 2011-05-04 | 华东理工大学 | Method for improving fermentation of erythromycin by adding dimethyl sulfoxide |
| CN102586366A (en) * | 2012-02-23 | 2012-07-18 | 安徽丰原发酵技术工程研究有限公司 | Method for producing erythrocin at high yield |
Non-Patent Citations (3)
| Title |
|---|
| 叶勇: "《制药工艺学》", 28 February 2014 * |
| 李雷等: "红霉素生产工艺的现状与展望", 《中国酿造》 * |
| 范代娣等: "红霉素摇瓶发酵实验工艺条件", 《西北大学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110452945A (en) * | 2018-05-07 | 2019-11-15 | 华东理工大学 | Utilize the novel method of S. erythraea fermentations production erythromycin |
| CN110452945B (en) * | 2018-05-07 | 2023-06-23 | 华东理工大学 | Method for producing erythromycin by fermenting saccharopolyspora erythraea |
| CN112553132A (en) * | 2019-09-25 | 2021-03-26 | 华东理工大学 | Optimized fermentation method of SacC gene knockout saccharopolyspora erythraea |
| CN110747246A (en) * | 2019-11-29 | 2020-02-04 | 宁夏启元药业有限公司 | Method for improving erythromycin fermentation unit |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109122050A (en) | A kind of cultural method of Cordyceps militaris | |
| CN101245362B (en) | Method for producing polypeptide antibiotic enramycin by fermentation method | |
| CN108085354A (en) | A kind of culture medium and its method of fermenting and producing FR901379 | |
| CN102161975A (en) | Streptomyces sp. GSDX-1318, and fermentation method for producing oligosaccharide antibiotic avilamycin | |
| CN105296571A (en) | Method for increasing erythromycin fermentation titer | |
| CN104388505A (en) | Method for producing nosiheptide from active streptomyces by virtue of fermentation | |
| CN102943101B (en) | Method for producing enramycin by fermenting | |
| CN101736071A (en) | Method for producing 2-keto-l-gulonic acid | |
| CN104388506A (en) | Method for producing nosiheptide employing fermentation of streptomyces actuosus | |
| CN104388501B (en) | A kind of erythromycin preparation method using biology enzyme | |
| CN108018324B (en) | Fermentation medium for producing doramectin and preparation method and application thereof | |
| CN107058414B (en) | Method for preparing L-alanine | |
| US2363227A (en) | Fermentation process for the production of riboflavin | |
| CN1282749C (en) | Course feeding fermentation method for preparing astaxanthin with molasses or starch sugar as materials | |
| CN110511974A (en) | A kind of fermentation process improving abomacetin fermentation potency | |
| CN103820510B (en) | A kind of fermentable produces method and the substratum of Lipstatin | |
| CN101186934A (en) | Continuous production method for L-ammonium lactate based on rhizopus | |
| CN106520871B (en) | Method for producing A40926 by fermentation method | |
| CN106360614A (en) | Method of preparing boletus edulis essential powder from boletus edulis deeply fermented mycelia | |
| CN108060192B (en) | Fermentation medium for improving fermentation level of meleumycin and feeding method | |
| CN104513845A (en) | Tetracycline fermentation feeding medium and feeding method | |
| CN113832205A (en) | Fed-batch fermentation method for producing amphotericin B in fermentation tank | |
| CN106676150A (en) | Method for producing natamycin by using streptomyces gilvosporeus through fermentation | |
| CN108949871A (en) | A kind of fermentation medium and its cultural method of fermenting and producing sulphur peptide antibiotics Nosiheptide | |
| CN108048503A (en) | The method for improving ansamitocin P-3 productions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160203 |