Medium for producing daunorubicin by fermenting streptomyces peucetius or streptomyces coeruleorubidus and fermentation method

A technology of streptomyces persei and fermentation medium, applied in the field of fermentation, can solve the problems of long daunorubicin fermentation cycle, high daunorubicin fermentation cost, and lack of market competitiveness, so as to improve market competitiveness and reduce Fermentation cost, improve the effect of effective guarantee

Active Publication Date: 2015-06-17
宁夏泰瑞制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004]1) The fermentation unit of daunorubicin is generally 1-3g / L due to the difference in the formula of the medium and the compatibility ratio of carbon source and nitrogen source, resulting in Unstable fermentation units
[0005]2) The fermentation period of daunorubicin is longer, with an average fermentation period of 150h
[0006]3) Combining the above factors, resulting in high energy consumption, high fermentation cost of daunorubicin, and lack of market competitiveness

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] The bacterial species is Streptomyces poseiian, and the titer of the shake flask is 43mg / L.

[0067] Configure primary seed medium 1m 3 , soybean oil 13L, formula molasses 15kg, glycerin 4L, earthworm powder 10kg, peptone 3kg, light calcium carbonate 2kg, ammonium sulfate 3kg.

[0068] Configure secondary seed medium 10m 3 : Soybean oil 160L, formula molasses 220kg, glycerin 80L, earthworm powder 140kg, peptone 60kg, potassium dihydrogen phosphate 4kg, light calcium carbonate 40kg, ammonium sulfate 40kg, sodium chloride 40kg, potassium chloride 60kg.

[0069] Configure fermentation medium 100m 3 : Soybean oil 2000L, formula molasses 3000kg, glycerin 1200L, earthworm powder 2000kg, peptone 1000kg, potassium dihydrogen phosphate 60kg, light calcium carbonate 600kg, ammonium sulfate 500kg, sodium chloride 400kg, potassium chloride 600kg, magnesium sulfate 600kg, chloride Iron 20kg, polyethylene diamine 1kg.

[0070] First-level seed cultivation process steps:

[0071]...

Embodiment 2

[0077] The strain is Streptomyces coelicolor, and the potency of the shake flask is 46mg / L.

[0078] Configure the primary seed medium group 1m 3 , corn oil 14L, formula molasses 16kg, glycerin 5L, earthworm powder 11kg, peptone 4kg, light calcium carbonate 3kg, ammonium sulfate 4kg.

[0079] Configure secondary seed medium 10m 3 : Corn oil 160L, formula molasses 230kg, glycerin 85L, earthworm powder 160kg, peptone 70kg, potassium dihydrogen phosphate 5kg, light calcium carbonate 50kg, ammonium sulfate 50kg, sodium chloride 45kg, potassium chloride 70kg.

[0080] Configure fermentation medium 100m 3 : Corn oil 2200L, formula molasses 3200kg, glycerin 1400L, earthworm powder 2200kg, peptone 1200kg, potassium dihydrogen phosphate 70kg, light calcium carbonate 700kg, ammonium sulfate 600kg, sodium chloride 450kg, potassium chloride 700kg, magnesium sulfate 700kg, chlorine Iron oxide 30kg, polyethylenediamine 1.5kg.

[0081] First-level seed cultivation process steps:

[0...

Embodiment 3

[0088] The bacterial species is Streptomyces poseiian, and the potency of the shake flask is 47mg / L.

[0089] Configure the primary seed medium group 1m 3 , soybean oil 15L, formula molasses 17kg, glycerin 6L, earthworm powder 12kg, peptone 5kg, light calcium carbonate 4kg, ammonium sulfate 5kg.

[0090] Configure secondary seed medium 10m 3 : Soybean oil 170L, formula molasses 250kg, glycerin 90L, earthworm powder 170kg, peptone 80kg, potassium dihydrogen phosphate 6kg, light calcium carbonate 60kg, ammonium sulfate 60kg, sodium chloride 50kg, potassium chloride 80kg.

[0091] Configure fermentation medium 100m 3 : Soybean oil 2300L, formula molasses 3300kg, glycerin 1400L, earthworm powder 2250kg, peptone 1300kg, potassium dihydrogen phosphate 80kg, light calcium carbonate 700kg, ammonium sulfate 800kg, sodium chloride 500kg, potassium chloride 800kg, magnesium sulfate 750kg, chloride Iron 40kg, polyethylenediamine 2kg.

[0092] First-level seed cultivation process st...

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Abstract

The invention relates to a medium for producing daunorubicin by fermenting streptomyces peucetius or streptomyces coeruleorubidus and a fermentation method. The medium comprises a primary seed medium, a secondary seed medium and a fermentation medium which all contain formula molasses, earthworm powder and glycerin, wherein the formula molasses comprise 0.07-0.09% of biotin, 0.02-0.05% of pantothenic acid, 0.04-0.07% of riboflavin, 0.01-0.02% of cane sugar invertase and the balance sugarcane molasses or beet molasses. By optimizing the fermentation medium formula and the fermentation technology of daunorubicin, the fermentation unit is improved, the fermentation period is shortened, the fermentation cost problem is solved, the environmental influence on sources of raw materials and auxiliary materials is furthest reduced, and the raw materials and the auxiliary materials are guaranteed to be sufficiently supplied, so that the stable efficient production of daunorubicin is realized.

Description

technical field [0001] The invention belongs to the technical field of fermentation, and in particular relates to a culture medium and a fermentation method for fermenting and producing daunorubicin by Streptomyces poseidoides or Streptomyces coelicolor. Background technique [0002] Daunorubicin is a secondary metabolite of Streptomyces poseidon or Streptomyces coelicolor, and its finished product is mainly used as a clinical first-line anticancer drug, and is widely used in the clinical treatment of tumors. [0003] At present, some domestic enterprises adopt traditional craft formula and three-stage fermentation mode to produce daunorubicin. The carbon sources are mainly starch and glucose, and the nitrogen sources are mainly bran and protein powder. The main problems are: [0004] 1) With different medium formulations and different compatibility ratios of carbon sources and nitrogen sources, the fermentation unit of daunorubicin is generally 1-3g / L, resulting in unstable...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/56C12R1/465
Inventor 任勇王义奇乃董媛李小萍
Owner 宁夏泰瑞制药股份有限公司
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