Fermentation method for production of gentamicin by continuous feed feeding with oxygen consumption rate as key control parameter

A technology for controlling parameters of gentamicin, which is applied in the fermentation field of continuous fed-batch feeding to produce gentamicin, achieving the effects of good operability, continuous production and resistance maintenance, and continuous increase in titer

Active Publication Date: 2021-07-06
QINGDAO INNOVATION INST OF EAST CHINA UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, some patents report that fermentation products adopt OUR as the key parameter of fermentation process control to control the fermentation process and achieve high yield (Patent No.: CN 103642870 A, CN 105154490 A, CN 108060144 A, CN 101560535 A, CN 102703540 A) , but there is no report to realize the optimal control of gentamicin fermentation process and increase the fermentation yield of gentamicin and improve its components by continuously feeding the OUR of the fermentation process

Method used

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  • Fermentation method for production of gentamicin by continuous feed feeding with oxygen consumption rate as key control parameter

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The strain used in this example is Micromonas aculeatus, which is a mature commercial fungus.

[0030] The entire fermentation process route is: shake flask seeds → primary seed cultivation → secondary seed cultivation → fermentation cultivation.

[0031] Medium composition:

[0032] Primary seed medium (g / L): glucose 1.4, corn starch 15, corn flour 20, angel peptone 2.6, low-temperature soybean flour 20, ammonium sulfate 2.5, potassium nitrate 0.054, calcium carbonate 6.2, foam enemy 0.03, silicone oil 0.05pH 7.2.

[0033] Secondary seed medium (g / L): corn starch 23, corn flour 30, angel peptone 13, bean cake powder 13, ammonium sulfate 5, magnesium sulfate 7.1, potassium nitrate 0.5, calcium carbonate 7, cobalt oxide 0.002, foam Enemy 0.05 and silicone oil 0.03, pH 7.8

[0034]Fermentation basal medium (g / L): corn starch 50, corn flour 20, medium temperature soybean powder 25, angel peptone 23, ammonium sulfate 5, magnesium sulfate 7.1, potassium nitrate 0.5, calci...

Embodiment 2

[0044] The primary seed culture and the secondary seed cultivation are the same as in Example 1, and the fermentation basal medium used in the primary seed medium, the secondary seed medium, and the fermentation culture process are also the same as in Example 1, but the OUR of continuous feeding control different. Feeding control strategy: According to OUR in the early stage of fermentation, when OUR drops to about 22mmol / kg / h, start to supplement sugar and nitrogen, and maintain OUR in the range of 18-20 during the fermentation process. According to the weighing of the fermenter, the volume is controlled at 30-35kg, and when it reaches about 35kg, 5kg is discharged.

Embodiment 3

[0046] The primary seed culture and the secondary seed cultivation are the same as in Example 1, and the fermentation basal medium used in the primary seed medium, the secondary seed medium, and the fermentation culture process are also the same as in Example 1, but the OUR of continuous feeding control different. Feeding control strategy: According to OUR in the early stage of fermentation, when OUR drops to about 28mmol / kg / h, start to supplement sugar and nitrogen, and maintain OUR in the range of 22-25 during the fermentation process. According to the weighing of the fermenter, the volume is controlled at 30-35kg, and when it reaches about 35kg, 5kg is discharged.

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Abstract

The invention relates to a fermentation method for the production of gentamicin by continuous feeding and feeding with the oxygen consumption rate as the key control parameter, including primary seed preparation, secondary seed preparation, and fermentation production process. Precisely control the rate of sugar supplementation or nitrogen supplementation rate in the process to achieve the purpose of regulating the oxygen consumption rate. When the OUR drops from the peak to the target OUR in the early stage of the fermentation process, start feeding, and maintain the OUR in the range of 15‑30 during the feeding process , so that the metabolic activity of the bacteria maintains the ability to continuously synthesize gentamicin. Compared with the prior art, the present invention realizes the process of OUR through continuous feeding, reaches the peak value after the initial cultivation and utilization, and then starts continuous feeding after different OURs to maintain the metabolic activity of the bacteria. , nutrition is continuously supplemented, the product synthesis is stable, the potency continues to increase, and the continuous production and resistance maintenance is very good. After adopting automatic control, the use of continuous feeding to maintain OUR is convenient for industrial scale control.

Description

technical field [0001] The invention belongs to the technical field of fermentation, and in particular relates to a fermentation method for producing gentamicin by continuous feeding and feeding with oxygen consumption rate as a key control parameter. Background technique [0002] Gentamicin is a broad-spectrum aminoglycoside antibiotic widely used in agriculture, medicine and feed industries with independent intellectual property rights in China; it currently occupies almost half of the global market for aminoglycoside antibiotics, and the domestic gentamicin API market has been The output value is close to 1 billion. Therefore, the research on its technology has important social and practical significance for improving the fermentation level and product quality of gentamicin in our country. [0003] The oxygen demand of bacteria in different fermentation stages is different, especially in the fermentation process of antibiotics; the supply of oxygen in the fermentation pr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/48C12R1/29
CPCC12P19/485
Inventor 李敏超张嗣良庄英萍储炬杭海峰
Owner QINGDAO INNOVATION INST OF EAST CHINA UNIV OF SCI & TECH
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