Method for improving lincomycin yield by fed-batch cultivation

A technology of lincomycin and yield, which is applied in the field of microbial fermentation, can solve problems such as adverse effects, achieve the effect of increasing potency and prolonging the fermentation cycle

Inactive Publication Date: 2014-05-21
SHANGHAI INST OF PHARMA IND CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The object of the present invention is to provide a kind of method of feed feeding in the fermentation process, to solve the unfavorable influence of feeding in batches on the fermentation of lincomycin

Method used

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  • Method for improving lincomycin yield by fed-batch cultivation
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  • Method for improving lincomycin yield by fed-batch cultivation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043]Example 1: Effects of glucose content on lincomycin fermentation titer, bacterial concentration and pH in shake flask fermentation

[0044] In the shake flask fermentation formula, under the condition of not changing other components, glucose with content of 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% was used as carbon source , to investigate the changes of lincomycin resistance level, biomass and pH in different fermentation cycles. from figure 1 , 2 , 3. It can be seen that because high concentration of sugar has a certain inhibitory effect on the growth of bacteria, the higher the initial glucose content in the medium, the slower the growth of the producing bacteria, and the initial resistance level of lincomycin is also correspondingly inhibited , which is mainly due to the lower biomass in the early stage and the glucose effect that exists when the sugar concentration is high. As the sugar in the medium is slowly utilized, when the concentration of res...

Embodiment 2

[0045] Example 2: Investigate the influence of dissolved oxygen on the fermentation titer of lincomycin in shake flask fermentation

[0046] In shake-flask fermentation, the effect of dissolved oxygen on the level of fermentation resistance was investigated mainly by changing the rotating speed of the shaker and the amount of liquid in the shake-flask. Under the condition that the amount of shaking bottle is 100ml / 750ml, the rotating speed of the shaking table is set to 150 rev / min, 180 rev / min, 200 rev / min, 220 rev / min and 250 rev / min respectively. At the same time, under the condition that the shaker speed is 250 rpm and the inoculum size is consistent, the liquid volume of the shaker bottle is 50ml / 750ml, 80ml / 750ml, 100ml / 750ml, 120ml / 750ml , 150ml / 750ml to investigate the fermentation titer of lincomycin in different cycles. from Figure 4 , 5 It can be seen that the higher the rotation speed of the shaker, the higher the level of resistance to lincomycin in the same c...

Embodiment 3

[0047] Embodiment 3: the application of fed-batch technology in 200L fermenter

[0048] The initial glucose content of the culture medium determined according to Example 1 was 3.0%. At the same time, according to Example 2, in the process control of the fermenter, by adjusting the stirring speed of the fermenter, the air flow rate and the feeding process in the middle and later stages to maintain a higher dissolved oxygen, it is beneficial to the improvement of the level of lincomycin production and resistance.

[0049] Fermenter basal medium (%): starch 0.5, glucose 3, cold-pressed soybean powder 0.9, compound protein powder 0.6, corn steep liquor 1.5, (NH 4 ) 2 SO 4 0.4, NaNO 3 0.4, NH 4 NO 3 0.4, NaCl0.5, KH 2 PO 4 0.05, CaCO 3 0.8, bubble enemy 0.035, silicone oil 0.025, pH6.5~7.5, sterilized at 121℃ for 30min.

[0050] Dilute medium (%): corn steep liquor 15.0, cold-pressed soybean powder 6.0, compound protein powder 4.0, CaCO 3 0.6, bubble enemy 0.1, silicone o...

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Abstract

The invention discloses a method for improving lincomycin by fed-batch cultivation. The method is characterized by comprising the step of feeding glucose and ammonium sulfate to a fermentation tank in a fermentation process, so as to improve the lincomycin yield. By adopting the method disclosed by the invention, the fermentation level of the lincomycin can be greatly improved.

Description

technical field [0001] The invention belongs to the technical field of microbial fermentation, in particular, the invention relates to a method for fermenting and producing lincomycin. Background technique [0002] Lincomycin is a lincosamide antibiotic, and it is one of the 20 most clinically used antibiotics. At present, in the fermentation production process of lincomycin, a relatively low initial sugar concentration is used, and the liquefied sugar (glucose), ammonium sulfate, and thinner are added in batches in the middle and later stages of fermentation. Some even sterilize by mixing liquefied sugar and ammonium sulfate in a certain proportion. In the sterilization process, melanoidin or melanoidin, a macromolecular substance produced by Maillard reaction between liquefied sugar and ammonium sulfate, may inhibit the biosynthesis of lincomycin, and greatly reduce the concentration of reducing sugar and ammonium sulfate. Effective utilization rate; on the other hand, i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/64C12R1/565
Inventor 李继安陈代杰林惠敏蓝鸿毛全贵张宏周
Owner SHANGHAI INST OF PHARMA IND CO LTD
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