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Method for increasing erythromycin fermentation titer

A technology of erythromycin and titer, which is applied in the field of improving the fermentation titer of erythromycin, can solve the problems of lack of dissolved oxygen, reduced dissolved oxygen concentration, and lack of dissolved oxygen in bacteria, so as to increase the vitality of bacteria and improve the level of fermentation. , the effect of prolonging the secretion period

Inactive Publication Date: 2016-02-03
NINGXIA QIYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the prior art, in the process of fermenting and producing erythromycin with Saccharopolyspora rubrum as the starting strain, a mixed nitrogen source and sugar water containing a large amount of late-acting nitrogen source and phosphorus element are added throughout the whole process. This method has the following technical disadvantages : 1) As the mycelium proliferates in large quantities, the volume increases in the middle and later stages, resulting in the lack of dissolved oxygen; 2) Due to the slow consumption of late-acting nitrogen sources, the residue at the end of fermentation is relatively large, which affects the extraction effect and the quality of the finished product; 3) Some bacteria The whole process of planting only needs to be supplemented with sugar water, and only a sufficient amount of nitrogen source is added to the base material, which will result in rich nutrition in the early stage, a large number of hyphae, a large amount of nitrogen source consumption, increased viscosity of the fermentation liquid, and increased surface tension of the fermentation liquid. The transfer efficiency decreases, the dissolved oxygen concentration decreases, resulting in the lack of dissolved oxygen in the bacteria, the lack of nitrogen source in the middle and later stages, the premature aging of mycelia, shortened fermentation cycle, and reduced yield

Method used

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  • Method for increasing erythromycin fermentation titer
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  • Method for increasing erythromycin fermentation titer

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preparation example Construction

[0018] Preparation method: use three-stage fermentation to produce erythromycin, and the specific steps are as follows:

[0019] 1. Preparation of slant spores: Inoculate Saccharopolyspora rubrum on a solid medium under aseptic conditions, culture at a constant temperature of 35°C for 6-8 days, and inoculate in a primary seed medium.

[0020] 2. The above slant spore culture medium was prepared according to conventional methods, and the formula was: starch 8g / L, ammonium sulfate 2.5g / L, sodium chloride 2.3g / L, calcium carbonate 2.4g / L, corn steep liquor 1.0g / L.

[0021] 3. First-level seed cultivation: Inoculate the slant spores grown in step 1 into the first-level seed medium in an aseptic manner, and cultivate at a constant temperature of 35°C with an aeration ratio of 1.5-2.0v / v / min and a stirring speed of 400-600r / min, cultivated for 40-60 hours.

[0022] 4. The above-mentioned primary seed culture medium is prepared by a conventional method, and its formula is starch 10...

Embodiment 1

[0030] 1. Take the secondary seed medium cultivated in step 5 of the above preparation method and inoculate it in the embodiment fermentation medium prepared in step 7 under aseptic conditions, cultivate according to normal culture conditions, and start to slowly add ammonium sulfate after fermentation until 60 hours solution, the concentration of the ammonium sulfate solution is 3-5%, and the feed rate per hour is controlled at 120-250L / hr according to the viscosity and the dissolved oxygen situation, and the feed rate is stopped at 140 hours, and the cumulative feed rate is 5% of the fermentation broth volume. -8%.

[0031] 2. Take the secondary seed medium cultured in step 5 of the above preparation method and inoculate it in the normal control fermentation medium prepared in step 7 under aseptic conditions, cultivate according to the normal culture conditions, and stop fermentation after 175 hours.

[0032]

Embodiment 2

[0034] 1. Take the secondary seed medium cultivated in step 5 of the above preparation method and inoculate it in the embodiment fermentation medium prepared in step 7 under aseptic conditions, cultivate according to normal culture conditions, and start to slowly add ammonium sulfate after fermentation until 60 hours Solution, the concentration of the ammonium sulfate solution is 6%, the feed rate per hour is controlled at 120-200L / hr according to the viscosity and the dissolved oxygen situation, and the feed rate is stopped at 140 hours, and the cumulative feed rate is 5-8% of the fermentation broth volume. %.

[0035] 2. Take the secondary seed medium cultured in step 5 of the above preparation method and inoculate it in the normal control fermentation medium prepared in step 7 under aseptic conditions, cultivate according to the normal culture conditions, and stop fermentation after 175 hours.

[0036]

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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 [0001] The invention relates to the field of microbial fermentation, in particular to a method for increasing the fermentation titer of erythromycin. Background technique [0002] Erythromycin is a macrolide antibiotic with an antimicrobial spectrum similar to that of penicillin. It is often used clinically for the treatment of patients allergic to penicillin. In recent years, due to the extensive development and use of erythromycin derivatives, the demand for erythromycin continues to increase. [0003] In the prior art, in the process of fermenting and producing erythromycin with Saccharopolyspora rubrum as the starting strain, a mixed nitrogen source and sugar water containing a large amount of late-acting nitrogen source and phosphorus element are added throughout the whole process. This method has the following technical disadvantages : 1) As the mycelium proliferates in large quantities, the volume increases in the middle and later stages, resulting in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/62C12R1/645
Inventor 章惠霞孙瑞君张志
Owner NINGXIA QIYUAN PHARMA
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