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A method for producing dalbavancin precursor a40926

A technology of A40926 and dalbavancin, which is applied in the field of biopharmaceuticals, can solve the problems of complicated operation, low yield of fermentation products, and poor feeding pertinence, and achieves the effect of reducing production cost and improving fermentation yield.

Active Publication Date: 2019-02-01
CHONGQING QIANTAI BIOLOGICAL MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] CN103060405A discloses an optimized fermentation process in which glucose, peptone and L-valine are added during the fermentation process, and the fermentation unit reaches 720 mg / L at the highest. This method greatly improves the fermentation unit of A40926 to a certain extent, but there are still supplements The problem of low material pertinence, complex operation, and low yield of fermentation products is needed, so it is necessary to further develop a method for improving the effect of A40926 fermentation units.

Method used

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  • A method for producing dalbavancin precursor a40926

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Methyl oleate solution of 10-methylundecanoic acid was added during fermentation

[0042] Prepare 300L seed medium in a 500L seed tank, sterilize at 120°C for 30 minutes, then cool to 28°C, inoculate 48h-old shake flask seeds at an inoculum volume ratio of 0.5% of the seed medium volume, and then incubate at 28°C for 72h.

[0043] Prepare 3500L fermentation medium in a 5000L fermenter, sterilize at 120°C for 30 minutes and cool to 26°C, insert the vegetative inoculum in the above seed medium with an inoculation amount of 8% by volume of the fermentation medium, and control the temperature during the fermentation process At 24~28°C, control the pressure at 0.04~0.06Mpa, control the ventilation at 0.5~1.5VVM, control the speed at 100~250rpm, and monitor the dissolved oxygen electrode online to ensure that the dissolved oxygen is above 30% (assuming the initial dissolved oxygen of the fermenter is 100%).

[0044] After 30 hours of fermentation, the PMV reached 2...

Embodiment 2

[0045] Example 2 Adding 10-sodium undecanoate solution during fermentation

[0046] Prepare 350L seed medium in a 500L seed tank, sterilize at 120°C for 30 minutes, cool to 28°C, inoculate 48h seed-age shake flask seeds at an inoculum volume ratio of 0.8% of the seed medium volume, and incubate at 28°C for 68h.

[0047] Prepare 3500L fermentation medium in a 5000L fermenter, sterilize at 120°C for 30 minutes and cool to 27°C, insert the vegetative inoculum in the above seed medium according to the inoculum volume ratio of 10% of the fermentation medium volume, and ferment during the fermentation process Control the temperature at 24~28°C, control the pressure at 0.04~0.06Mpa, control the ventilation at 0.5~1.5VVM, control the speed at 100~250rpm, and monitor the dissolved oxygen electrode online to ensure that the dissolved oxygen is above 30% (assuming that the fermentation tank The initial dissolved oxygen is 100%).

[0048] Fermentation 40h, PMV reaches 25%, begins to add ...

Embodiment 3

[0049] Example 3 Adding 10-methylammonium undecylate solution during fermentation

[0050] Prepare 600L seed medium in a 1T seed tank, sterilize at 120°C for 30 minutes, then cool to 28°C, inoculate 48h-old shake flask seeds at an inoculum volume ratio of 0.3% of the seed medium, and then culture at 28°C for 72h.

[0051] Prepare 10,000L fermentation medium in a 20T fermenter, sterilize at 120°C for 30 minutes and cool to 26°C, add the vegetative inoculum in the above seed medium according to the inoculum volume ratio of 5% of the fermentation medium volume, and ferment during the fermentation process Control the temperature at 24~28°C, control the pressure at 0.04~0.06Mpa, control the ventilation at 0.5~1.5VVM, control the speed at 100~250rpm, and monitor the dissolved oxygen electrode online to ensure that the dissolved oxygen is above 30% (assuming that the fermentation tank The initial dissolved oxygen is 100%).

[0052] Fermentation 48h, PMV reaches 21%, begins to add 15...

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Abstract

The invention discloses a method of producing a dalbavancin precursor A40926. In particular, during a fermentation cultivation proves, 10-methyl undecanoic acid, or several 10-methyl undecanoic undecanoate solutions, is flow-fed to a fermentation liquid to increase the yield of the dalbavancin precursor A40926. The method is simple in operation, greatly increases fermentation yield, reduces production cost and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a method for producing dalbavancin precursor A40926. Background technique [0002] Dalbavancin is a new generation of glycopeptide antibiotics, belonging to the same class as vancomycin and remoplanin. This class of antibiotics is used to treat the most difficult bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). In vitro experiments have shown that in addition to enhanced bactericidal activity against common Gram-positive bacteria in clinical practice, dalbavancin has a longer half-life and better tissue penetration, so that patients have greater flexibility in drug administration. Preclinical and clinical studies conducted to date show that dalbavancin is one of the most active antibiotics against MRSA and MRSE without causing significant dose-limiting adverse reactions. [0003] Dalba...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P21/00C12R1/01
Inventor 别一郭明袁建栋
Owner CHONGQING QIANTAI BIOLOGICAL MEDICINE
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