Method for controlling fermentation of macrolide antibiotics

A technology of macrolides and macrolides, which is applied in the field of fermentation regulation of macrolide antibiotics based on culture temperature regulation, can solve the problem of rising, difficulty in controlling the fermentation process, and inability to continuously meet the needs of product synthesis, etc. problems, to achieve the effect of reducing consumption, improving equipment utilization, and easy control

Pending Publication Date: 2020-07-17
CHENGDU UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the middle and late stages of fermentation, if the fermentation temperature is continued to be high, the microorganisms will quickly consume the raw materials that produce short-chain fatty acid units, such as sugar, oil, or amino acids, which will be lost as waste, and cannot continue to meet the needs of product synthesis.
At the same time, high carbon source consumption will produce a large amount of organic acids, which will cause the pH and dissolved oxygen of the fermentation broth to drop rapidly, and the pH value will rise rapidly after the carbon source is exhausted, which will make the fermentation process difficult to control

Method used

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  • Method for controlling fermentation of macrolide antibiotics
  • Method for controlling fermentation of macrolide antibiotics
  • Method for controlling fermentation of macrolide antibiotics

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Bacteria: Streptomyces avermitilis Streptomyces avermitilis SIIA-1502

[0022] Proportion of fermentation medium:

[0023]

[0024] Accurately weigh the starch according to the specified ratio and put it into the fermentation batching tank (add appropriate amount of water in advance), start stirring, add amylase (0.5% of the weight of starch) and steam to heat, gradually raise the temperature to 85°C, keep stirring for 60 minutes, so that the starch is fully liquefaction. Put the above ingredients into the batching tank and add water to a constant volume, stir for 15 minutes and measure the pH, the pH should be 6.9, heat up, and when the temperature reaches 121°C, start to sterilize for 30 minutes.

[0025] Fermentation volume: 6000L;

[0026] Inoculation amount: 10 eggplant bottles;

[0027] Stirring speed: 80-220rpm;

[0028] Air flow: 1:0.5-0.8vvm;

[0029] Culture cycle: 315 hours.

[0030] In the early 80 hours of the fermentation of the abamectin-produc...

Embodiment 2

[0049] Strains: Actinomycetes mobilis SIIA-1602 ( Actinoplanes SIIA-1602)

[0050] Proportion of fermentation medium:

[0051]

[0052] Accurately weigh the starch according to the specified ratio and put it into the fermentation batching tank (add appropriate amount of water in advance), start stirring, steam heating, gradually raise the temperature to 70°C, keep stirring for 10 minutes, so that the starch is fully gelatinized. Put the above ingredients into the batching tank and add water to a constant volume, stir for 15 minutes, then measure the pH, the pH should be 6.9, heat up, and when the temperature reaches 121°C, start to sterilize for 30 minutes.

[0053] Fermentation volume: 6000L;

[0054] Inoculation amount: 8%;

[0055] Stirring speed: 80-220rpm;

[0056] Air flow: 1:0.5-0.8vvm;

[0057] Culture cycle: 220 hours.

[0058] In the early stage of 0-60 hours of fermentation of the sirolimus-producing bacteria, the mycelium is rapidly grown through the basal...

Embodiment 3

[0075] Strain: New species of Streptomyces thousand Buddha SIIA-9818 ( Streptomyces qianfoensis sp.nov. SIIA-9818)

[0076] Proportion of fermentation medium:

[0077]

[0078] Accurately weigh the starch according to the specified ratio and put it into the fermentation batching tank (add appropriate amount of water in advance), start stirring, steam heating, gradually raise the temperature to 70°C, keep stirring for 10 minutes, so that the starch is fully gelatinized. Put the above ingredients into the batching tank and add water to a constant volume, stir for 15 minutes and measure the pH, the pH should be 6.9, heat up, and when the temperature reaches 121°C, start to sterilize for 30 minutes.

[0079] Fermentation volume: 6000L;

[0080] Inoculation amount: 8%;

[0081] Stirring speed: 80-220rpm;

[0082] Air flow: 1:0.8-1.0vvm;

[0083] Culture cycle: 220 hours.

[0084] In the early stage of fermentation of tacrolimus-producing bacteria for 0-48 hours, the myce...

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Abstract

The invention relates to a method for controlling fermentation of macrolide antibiotics, and solves the problems that the fermentation process of a traditional method is not easy to control, energy consumption is high, and the yield of a target product is low. The method comprises the following steps: controlling the culture temperature at 27.0-30.0 DEG C according to normal requirements in the primary metabolism stage of macrolide antibiotic producing bacteria, and rapidly growing hypha; and reducing the fermentation culture temperature to 18.0-27.0 DEG C after the logarithmic growth phase ofthe macrolide antibiotic producing bacteria is completed, and promoting mass synthesis of the target product, wherein the macrolide antibiotic is an antibiotic produced by fermentation by adopting aPKS biosynthesis pathway and a homologue of the antibiotic. The method has a simple and easy process, is easy to operate, and is very suitable for commercial production.

Description

technical field [0001] The invention relates to the technical field of microbial medicines, in particular to a method for regulating the fermentation of macrolide antibiotics based on cultivation temperature regulation. Background technique [0002] Macrolide antibiotics such as Sirolimus, Tacrolimus, Doramectin, Spinosyn and Kitasamycin are structurally They are all polyketides, and the biosynthesis process of this polyketide structure also shows similar rules. Polyketide synthase (polyketidesynthase, PKS) is a multi-enzyme complex that catalyzes the formation of polyketide compounds, and catalyzes the synthesis of macrolide antibiotics, which are polymerized from lower fatty acids and have a basic skeleton with a long carbon chain structure. The initial unit of polyketide synthesis and short-chain fatty acid units such as acetic acid and propionic acid required for carbon chain extension have been accumulated in the stage of microbial primary metabolism. In the middle an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/18C12P19/62C12N1/20C12R1/465C12R1/045C12R1/01
CPCC12N1/20C12P17/188C12P19/62C12P19/623
Inventor 王欣荣张雪霞褚以文郑智慧张新宜路新华赵克雷高健林家富黄挺任凤芝翟龙飞任乐民刘超兰宋涛
Owner CHENGDU UNIV
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