Process for producing salinomycin based on metabolizing parameter respiratory quotient (RQ) carbohydrate supplementation fermentation

A technology for salinomycin and sugar supplementation, which is applied in the field of salinomycin production based on metabolic parameter RQ supplementation and fermentation, and can solve the problem of increased salinomycin fermentation cost, reduced dissolved oxygen in fermentation system, unfavorable bacterial metabolism, etc. problems, to achieve the effect of reducing dissolved oxygen, mature technology and reducing production costs

Active Publication Date: 2014-01-01
内蒙古拜克生物有限公司
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

[0003] At present, the production of salinomycin is mainly carried out through biological fermentation, mainly using soybean oil and palm oil as its main fermentation carbon source, such as disclosed in Chinese patent CN1230596, but as the price of oil continues to rise in recent years, salinomycin The fermentation cost of the element has been greatly improved; and due to the characteristics of the oil itself, the accumulation of too much oil in the fermentation substrate will reduce the dissolved oxygen in the fermentation system, and at the same time, it will also adhere to the surface of the mycelium, which is not conducive to bacterial growth. Body metabolism, and even the phenomenon of agglomeration of fermentation broth

Method used

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  • Process for producing salinomycin based on metabolizing parameter respiratory quotient (RQ) carbohydrate supplementation fermentation

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Experimental program
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Effect test

Embodiment 1

[0034] Use media component 1

[0035] (1) Slant culture: Inoculate the Streptomyces albicans strain on a fresh slant and culture at 26°C for 8 days;

[0036] (2) Seed cultivation: insert the spores obtained in step (1) into the seed medium, and cultivate for 30 hours at 30°C and 260 r / min;

[0037] (3) Fermentation culture: Inoculate the seed liquid obtained in step (2) into a fermenter (15L tank, about 8 liters of fermentation medium after sterilization), the inoculation amount is 8%, the culture temperature is 30-35°C, the pressure is 0.05MPa, DO Control at 30-40%, speed 400-500rpm, when RQ drops to 0.65, start to add 20% sucrose aqueous solution with 10ml / H feeding method, when RQ value rises to 0.9, add 5- 8ml / H fed-batch feeding added 20% sucrose by mass percentage to control the RQ value at 0.85-0.95. After 290 hours of fermentation, put it into the tank.

Embodiment 2

[0039] Use media component 2

[0040] (1) Slant culture: Inoculate the Streptomyces albicans strain on a fresh slant and culture at 30°C for 6 days;

[0041] (2) Seed cultivation: insert the spores obtained in step (1) into the seed medium, and cultivate for 30 hours at 35°C and 220 r / min;

[0042] (3) Fermentation culture: inoculate the seed liquid obtained in step (2) into a fermenter (30L tank, about 16 liters of fermentation medium after sterilization), the inoculation amount is 12%, the culture temperature is 30-35°C, the pressure is 0.06MPa, DO Control at 80-100%, speed 250-300rpm, when RQ drops to 0.65, start to add 15mL / H glucose solution with a mass percentage of 15%, when RQ value rises to 0.8, add 12mL The / H flow is supplemented with 15% glucose aqueous solution, and the RQ value is controlled at 0.68-0.8. After 300 hours of fermentation, put it into the tank.

Embodiment 3

[0044] Use media component 3

[0045] (1) Slant culture: Inoculate the Streptomyces albicans strain on a fresh slant and culture at 28°C for 7 days;

[0046](2) Seed cultivation: insert the spores obtained in step (1) into the seed medium, and cultivate for 30 hours at 32°C and 240 r / min;

[0047] (3) Fermentation culture: inoculate the seed liquid obtained in step (2) into a fermenter (50L tank, about 24 liters of fermentation medium after sterilization), the inoculum amount is 10%, the culture temperature is 30-35°C, the pressure is 0.04MPa, DO Control at 60-80%, speed 300-400rpm, when RQ drops to 0.65, start to add 20% soluble starch aqueous solution by mass percentage at 10mL / H, when RQ value rises to 0.8, add 5mL The / H feed adds 20% soluble starch aqueous solution to control the RQ value at 0.7-0.8. After 310 hours of fermentation, put it into the tank.

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Abstract

The invention discloses a process for producing salinomycin based on metabolizing parameter respiratory quotient (RQ) carbohydrate supplementation fermentation, which comprises the following steps of conducting fermentation cultivation; and inoculating seed liquid obtained by slant culture and seed culture to a fermentation tank, enabling the inoculum size to be 8-12%, enabling culture temperature to be 30-35 DEG C, enabling pressure to be 0.04-0.06 MPa, enabling DO to be controlled in 30%-100%, enabling rotation speed to be 250-500 rpm, beginning to adding carbohydrate supplementation when the RQ drops to a state lower than or equal to 0.65, enabling the RQ value to be controlled in 0.68-0.95, and placing a tank after 290-310 hours after fermentation begins. The process conducts flow-adding-type carbohydrate supplementation with the RQ value serving as operation indexes in the middle stage and later stage, reduces production cost of the salinomycin while stably improving titer, solves the technical problem that dissolved oxygen of a fermentation system is reduced caused by accumulation of excessive oil in a fermentation substrate, solves the technical problem of agglomeration of fermentation broth, and is mature in technique and suitable to industrial mass production.

Description

technical field [0001] The invention relates to a method for optimizing the fermentation process of salinomycin, in particular to a process for producing salinomycin based on metabolic parameter RQ sugar supplementation fermentation. Background technique [0002] Salinomycin is a polyether monocarboxylic acid antibiotic with a special ring structure and is a typical ionophore antibiotic. Salinomycin is a polyether ionophore-type animal-specific antibiotic produced by Streptomysis albus. It has been recognized by the majority of breeders due to its broad-spectrum and high-efficiency anti-coccidiosis performance. [0003] At present, the production of salinomycin is mainly carried out through biological fermentation, mainly using soybean oil and palm oil as its main fermentation carbon source, such as disclosed in Chinese patent CN1230596, but as the price of oil continues to rise in recent years, salinomycin The fermentation cost of the element has been greatly improved; and...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/18C12R1/47
Inventor 沈建姚云泉高圣君储消和黄海涛生英涛王克非
Owner 内蒙古拜克生物有限公司
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