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A kind of preparation method of defoamer for fermented production of epothilone

A technology for epothilone and antifoaming agent is applied in the field of preparation of antifoaming agent for fermentative production of epothilone, and can solve the problems of reducing the charging coefficient, disturbing fermentation by foam, and not finding epothilone A.

Active Publication Date: 2022-07-12
山西博鑫生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] CN109837225A discloses a strain of epothilone D high-yielding bacteria and its application in fermenting and producing epothilone D. The strain is classified as Sporangium cellulosum SPD-1935 and has been preserved in China's typical culture CCTCC, Collection Number: CCTCC NO: M2018531, in the shaking table fermentation experiment, the mutagenic strain epothilone D reached 436.27mg / L, which was 323 times higher than the 1.35mg / L yield of the original strain; At the same time, a trace amount of epothilone C was found in the detection process, but no production of epothilone A and B was found
[0007] The above inventions and existing technologies show that the current production of epothilone is mainly obtained by microbial fermentation, but in the fermentation process, foam has always been a problem that plagues fermentation
If the foam is not properly controlled and the foam overflows, it will cause a series of problems: a large amount of escape reduces the filling coefficient, increases the risk of bacterial contamination, causes waste of raw materials and loss of products, etc.
The difference from other microorganisms is that the foam produced by Epothilone, Sonocystis cellulose, is difficult to eliminate during the liquid fermentation process, and has strong regeneration ability. The addition of a large amount of defoaming agent will affect the normal growth of microorganisms and metabolism, limiting the production of epothilone

Method used

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  • A kind of preparation method of defoamer for fermented production of epothilone
  • A kind of preparation method of defoamer for fermented production of epothilone

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Embodiment 1

[0026] A kind of preparation method of defoamer for fermented production of epothilone, its concrete scheme is as follows:

[0027] According to the parts by mass, 8g di(ethylene glycol) ethyl ether methacrylate, 55g terminal epoxy silicone oil, 0.8g mercapto-dipolyethylene glycol-tert-butyl propionate and 0.06g 1-methylimidazole hydrochloride Add it to the reaction kettle, the stirring speed is 70r / min, the system temperature is maintained at 120°C, and the reaction is carried out for 2h under the condition of vacuum degree of 0.06MPa under reduced pressure and reflux to obtain di(ethylene glycol) ethyl ether methacrylate modified silicone oil; after completion Add 10g phosphorylated polyether modified amino silicone oil, 18g silicon dioxide, 3g ultrafine aluminum silicate, stir evenly, then heat up to 110°C, the reaction time is 2h, then add 0.6g malonic acid and 0.2g citric acid, The wood plywood board was reacted at a temperature of 80°C for 30min, cooled to 60°C, added 2....

Embodiment 2

[0036] A kind of preparation method of defoamer for fermented production of epothilone, its concrete scheme is as follows:

[0037] According to the parts by mass, 10g of di(ethylene glycol) diethyl ether methacrylate, 58g of terminal epoxy silicone oil, 1.2g of mercapto-dipolyethylene glycol-tert-butyl propionate and 0.1.8g of 1-methylimidazole hydrochloride The salt was added to the reaction kettle, the stirring speed was 80 r / min, the system temperature was maintained at 130 ° C, and the reaction was carried out for 3 h under the condition of vacuum degree of 0.07 MPa under reduced pressure and reflux to obtain di(ethylene glycol) ethyl ether methacrylate modified silicone oil; complete; Then add 14g phosphorylated polyether modified amino silicone oil, 22g silicon dioxide, 5g ultrafine aluminum silicate, stir evenly, then heat up to 130 ℃, the reaction time is 3h, then add 1.2g malonic acid and 0.5g citric acid , the temperature is controlled at 90 ℃, the wood plywood is r...

Embodiment 3

[0046] A kind of preparation method of defoamer for fermented production of epothilone, its concrete scheme is as follows:

[0047] According to the parts by mass, 12g di(ethylene glycol) ethyl ether methacrylate, 68g terminal epoxy silicone oil, 1.6g mercapto-dipolyethylene glycol-tert-butyl propionate and 0.24g 1-methylimidazole hydrochloride Add it to the reaction kettle, the stirring speed is 90r / min, maintain the system temperature at 140°C, and react for 5h under the condition of vacuum degree of 0.09MPa under reduced pressure and reflux to obtain di(ethylene glycol) ethyl ether methacrylate modified silicone oil; after completion Add 18g phosphorylated polyether modified amino silicone oil, 26g silicon dioxide, 8g ultrafine aluminum silicate, stir evenly, then heat up to 140 ° C, the reaction time is 5h, then add 1.8g malonic acid and 0.8g citric acid, The wood plywood board was reacted at a temperature of 110°C for 60min, cooled to 80°C, added 3.6g of surfactant, stirr...

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Abstract

The invention relates to the field of microbial fermentation, in particular to a preparation method of a defoamer for fermentative production of epothilone; the invention firstly synthesizes di(ethylene glycol) ethyl ether methacrylate modified silicone oil, and then mixes it with a phosphoric acid The phosphorylated polyether-modified aminosilicone oil was mixed with solid powder and reacted to prepare a defoamer suitable for the fermentation of Cystobacter celluliformis. The phosphorylated polyether-modified aminosilicone oil had a branched structure and excellent Shear resistance, suitable for the environment in the fermentation broth; in addition, the addition of polyether structure is beneficial to increase the hydrophilicity of the defoamer, increase the dispersibility of the defoamer in the fermentation broth, and is conducive to enhancing the defoaming Foam-inhibiting ability; the defoamer of the present invention has a promoting effect on the growth of C. cellulosum and the production of epothilone, and is a defoamer product suitable for the fermentation liquid of C. cellulosum.

Description

technical field [0001] The invention relates to the field of microbial fermentation, in particular to a preparation method of a defoamer for fermentative production of epothilone. Background technique [0002] Epothilone was first discovered and isolated from Cystobacter fibroblasts, and it was found to have antifungal activity. After structural identification, it was a macrolide polyketide compound with microtubule polymerization-promoting activity. It has become one of the research hotspots that can have an effect on microtubule polymerization after paclitaxel. [0003] CN101104864B relates to the preparation method of epothilone B. Specifically, the invention provides a technical method for preparing epothilone B by large-scale fermentation in a 100-liter to 500-liter fermentor and a large amount of separation. The invention also relates to a preparation of epothilone B and its application in the preparation of a drug for treating Gleevec-resistant chronic myeloid leuke...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): B01D19/04C08G77/46
CPCB01D19/0409B01D19/0418C08G77/46
Inventor 周珍珍其他发明人请求不公开姓名
Owner 山西博鑫生物科技有限公司
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