Unlock instant, AI-driven research and patent intelligence for your innovation.

Fermentation method for producing gentamicin by continuous feeding with oxygen uptake rate as key control parameter

A technology for controlling parameters and oxygen consumption rate, which is applied in the field of fermentation to achieve stable product synthesis, increased C1a content, and sustained production and maintenance of resistance.

Active Publication Date: 2019-12-10
QINGDAO INNOVATION INST OF EAST CHINA UNIV OF SCI & TECH +1
View PDF8 Cites 2 Cited by
  • 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, CN108060144 A, CN 101560535 A, CN 102703540 A), However, there is no report to realize the optimal control of gentamicin fermentation process and increase the fermentation yield of gentamicin and improve its components through continuous feeding to control the OUR of the fermentation process.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Fermentation method for producing gentamicin by continuous feeding with oxygen uptake 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, calciu...

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 supplementing 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.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a fermentation method for producing gentamicin by continuous feeding with an oxygen uptake rate (OUR) as a key control parameter. The fermentation method comprises a primary seed preparation, a secondary seed preparation and a fermentation production process. In the fermentation production process, a purpose of regulating and controlling the oxygen uptake rate is realizedby accurately controlling a carbohydrate supplement rate or a nitrogen supplement rate in fermentation process. In early stage of the fermentation process, when the OUR decreases from a peak value toa target OUR, feeding is started. During the feeding process, the OUR is maintained within a range of 15-30, so that metabolic activity of bacteria is maintained to make the bacteria have an ability to continuously synthesize gentamicin. Compared with the prior art, according to the method, regulation of OUR in the fermentation process is achieved through continuous feeding, the metabolic activityof bacteria is maintained, after entering a secondary metabolic antibiotic-producing stage in middle and later stages, nutrition is continuously supplemented, product synthesis is stable, titer is continuously increased, and continuous antibiotic-production is maintained very well. The method adopts automatic control and continuous feeding to maintain OUR, and 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 flow 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 my 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 proces...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(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