CN102234673B - Fermentation culture medium and fermentation method for producing pentostatin by fermentation of streptomyces antibioticus - Google Patents
Fermentation culture medium and fermentation method for producing pentostatin by fermentation of streptomyces antibioticus Download PDFInfo
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Abstract
The invention provides a fermentation culture medium and a fermentation method for producing pentostatin by fermentation of streptomyces antibioticus. The fermentation culture medium comprises a carbon source and a nitrogen source, wherein based on the total weight of the culture medium, the content of the carbon source is 0.5-14%, and the content of the nitrogen source is 0.5-10%; and the carbon source is one or more of glucose, dextrin and wheat starch, and the nitrogen source is one or more of fine bean pulp powder, soy protein, soybean cake powder, yeast soaking powder and cotton seed cake powder. According to the invention, the yield of pentostatin is greatly improved through optimizing the fermentation parameters of the fermentation culture medium, such as components and proportioning of the carbon and nitrogen sources, culture temperature, pH and the like. By using the fermentation production method of pentostatin, the fermentation unit of pentostatin is greatly improved, and the fermentation method is suitable for large scale production of pentostatin.
Description
Technical field
The invention belongs to industrial microbial technology field, particularly a kind of fermention medium of new antibiosis streptomycete fermentative production pentostatin and corresponding fermentation process.
Background technology
The Woo of warner lambert company in 1974 etc. finds a kind of adenosine deaminase inhibitors-pentostatin from Streptomyces antiboticus fermented liquid.Pentostatin treatment for stem cell leukemia (hairy cell leukemia, HCL) by FDA approval in 1992.Along with the increase to its clinical application, market demand strengthens.But at present to the report of pentostatin production research seldom, the zymotechnique of unique report sees US3923785, in this patent, take antibiosis streptomycete NRRL3238 as producing bacterial classification, a kind of better simply substratum and training method have mainly been reported, its objective is for from separation of fermentative broth to pentostatin, to carry out Structural Identification and biological activity assay.Because the culture process of this patent is too simple, the fermentation unit of product is lower, is not suitable for the production of mass-producing pentostatin.
Summary of the invention
Therefore, the technical problem to be solved in the present invention is exactly for the existing low deficiency of antibiosis streptomycete fermentative production pentostatin fermentation unit of utilizing, a kind of fermention medium and corresponding fermentation process of new antibiosis streptomycete fermentative production pentostatin are provided, it can improve the fermentation unit of pentostatin greatly, enhances productivity.
The present invention solves the problems of the technologies described above one of adopted technical scheme: a kind of fermention medium for antibiosis streptomycete (Streptomyces antibioticus) fermentative production pentostatin, comprise Carbon and nitrogen sources, wherein by the gross weight of substratum, the content of described carbon source is 0.5～14%, the content of described nitrogenous source is 0.5～10%, described carbon source is selected from one or more in glucose, dextrin and wheat starch, and described nitrogenous source is selected from thin bean cake powder, soybean protein, soybean cake powder, yeast and soaks one or more in powder and cotton seed powder cake.
In fermention medium of the present invention, the content of described carbon source is 0.5～14%, and preferably scope is 1～6%.
In fermention medium of the present invention, described nitrogenous source is selected from thin bean cake powder, soybean protein, soybean cake powder, yeast and soaks one or more in powder and cotton seed powder cake.More preferably be selected from the mixture that one or more and yeast in thin bean cake powder, soybean protein, soybean cake powder and cotton seed powder cake soaks powder.Best is the mixture that thin bean cake powder and yeast soak powder.The content of described nitrogenous source is 0.5～10%, and preferably scope is 1～6%.
In fermention medium of the present invention, as the fermention medium of conventional antibiosis streptomycete, also contain mineral substance.The content of mineral substance preferably 0.1%～1%.Described mineral salt can be the various mineral salts that use in the fermention medium of conventional antibiosis streptomycete, generally as osmotic pressure regulator, and preferably NaCl.
Fermention medium of the present invention, as the fermention medium of conventional antibiosis streptomycete, preferably can also further contain trace somatomedin.
Fermention medium of the present invention, as the fermention medium of conventional antibiosis streptomycete, preferably can also contain defoamer.
A preferred embodiment of the present invention is that fermention medium of the present invention comprises:
0.5～14% carbon source, described carbon source is selected from one or more in glucose, dextrin and wheat starch;
0.5～10% thin bean cake powder, soybean protein, soybean cake powder and/or cotton seed powder cake;
0.1～1% yeast soaks powder; With
0.1～1% mineral salt.
The pH value of fermention medium of the present invention is pH5.0-8.0, more preferably pH5.5-7.5 preferably.
The present invention solves the problems of the technologies described above two of adopted technical scheme: a kind of fermentation method for producing of pentostatin, comprises step:
(a) seed liquor of antibiosis streptomycete (Streptomyces antibioticus) is inoculated in fermention medium and carries out liquid fermentation and culture, described fermention medium is fermention medium claimed in claim 1;
(b) from fermented liquid, isolate pentostatin.
In step (a), the seed liquor of described antibiosis streptomycete is that antibiosis streptomycete method is routinely cultivated antibiosis streptomycete to be obtained in seed culture medium.Described seed culture medium can be the seed culture medium of existing antibiosis streptomycete, preferably comprises 2% glucose, 2% soybean cake powder 0.5%NaCl, 0.25%CaCO
3.Preferably 25～30 ℃ of the temperature of seed culture.
In the present invention, described antibiosis streptomycete can be existing various antibiosis streptomycete bacterial strain, preferably antibiosis streptomycete NRRL3238.
In step (a), the temperature of described fermentation culture is 20～40 ℃, is preferably 25～37 ℃; Preferred pH5～8 are preferably pH5.5～7.5.
In step (b), the method for isolating from fermented liquid in pentostatin is conventional method, is generally by fermented liquid centrifuging and taking supernatant, through the wash-out of drainage column, and then crystallization of concentrated decolouring, thus obtain pentostatin.
In the present invention, above-mentioned optimum condition can arbitrary combination on the basis that meets this area general knowledge, obtains the preferred embodiments of the invention.
The present invention is except special instruction, and per-cent used is all weight percent (wt).
The raw material that the present invention is used or reagent except special instruction, equal commercially available obtaining.
Than prior art, beneficial effect of the present invention is as follows: the invention provides a kind of fermention medium and corresponding fermentation process that antibiosis streptomycete high-efficiency fermenting is produced pentostatin that be conducive to.By carbon nitrogen source composition and the proportioning of preferred fermention medium, optimize the fermentation parameters such as culture temperature, pH, thereby greatly improve the output of pentostatin.Fermentation method for producing provided by the invention has significantly improved the fermentation unit of pentostatin, is applicable to the large-scale production of pentostatin.
Embodiment
With embodiment, further illustrate the present invention below, but the present invention is not limited.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, or the condition of advising according to manufacturer.
Pentostatin assay in fermented liquid: get appropriate fermented liquid during fermentation ends, through the centrifugal 10min of 12000rpm, get supernatant liquor and detect for high pressure liquid chromatography after 0.45 μ m filtering with microporous membrane.Chromatographic condition: chromatographic column: Hypersil ODS2 post (5 μ m, 4.6mm * 250mm); Moving phase: methyl alcohol-acetonitrile-10mmol/L ammonium acetate (2.5: 2.5: 95) (PH=7.6); Flow velocity: 1.0mL/min; Wavelength: 280nm; Column temperature: 40 ℃; Sample size: 10 μ L, pentostatin goes out peak about 7 minutes.
Embodiment 1
Get a strain antibiosis streptomycete (Streptomyces antibioticus) NRRL3238 (purchased from USDA DSMZ) and line seed slant medium, after 28 ℃ of cultivation 7d, be inoculated in seed culture medium, loading amount is 20ml/250ml, in 30 ℃, the rotary shaking table of 250rpm is cultivated 36h.The ferment-seeded making is inoculated in the 5L fermentor tank that contains 2L substratum with 1% (v/v) inoculum size, and controlled fermentation temperature is 30 ℃ automatically, pH6.5, and rotating speed is associated with dissolved oxygen, and maintaining dissolved oxygen is 40%, air flow 0.5VVM.24h starts stream and adds glucose 1～10 ‰ L/h, fermentation period 72h.The output of pentostatin reaches 50mg/L.
Wherein slant medium used forms: glucose 4.0g/L, and yeast soaks powder 4.0g/L, and Fructus Hordei Germinatus soaks powder 10.0g/L, agar powder, 20.0g/L, pH nature.
Seed culture medium used forms: 2% glucose, 2% soybean cake powder 0.5%NaCl, 0.25%CaCO
3, pH nature.
Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.
Embodiment 2
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 10.0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 20mg/L.
Embodiment 3
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 60.0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 30mg/L.
Embodiment 4
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: dextrin 60.0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 35mg/L.
Embodiment 5
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: dextrin 20.0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 25mg/L.
Embodiment 6
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: DEXTRIN .0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 30mg/L.
Embodiment 7
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 10.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH7.0, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 20mg/L.
Embodiment 8
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 60.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.0, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 35mg/L.
Embodiment 9
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM.Fermentation period 72h, the output of pentostatin reaches 30mg/L.
Embodiment 10
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and soybean protein 60.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 35mg/L.
Embodiment 11
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, thin beans cypress 30.0g/L, soybean protein 20g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH5.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 25mg/L.
Embodiment 12
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 37 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 45mg/L.
Embodiment 13
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 25 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 30mg/L.
Embodiment 14
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH5.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 40mg/L.
Embodiment 15
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH7.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 45mg/L.
Embodiment 16
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in 50L bio-reactor.Fermention medium forms: glucose 40.0g/L, and thin beans cypress 30.0g/L, soybean protein 20g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L, bubble enemy 0.05g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 55mg/L.
Embodiment 17
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: wheat starch 40.0g/L, and thin beans cypress 30.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 25mg/L.
Embodiment 18
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: wheat starch 10.0g/L, and cottonseed meal 60.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 20mg/L.
Embodiment 19
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: wheat starch 60.0g/L, and soybean cake powder 20.0g/L, yeast soaks powder 5.0g/L, NaCl 5.0g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 20mg/L.
Embodiment 20
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 5g/L, and thin beans cypress 30g/L, yeast soaks powder 5g/L, NaCl5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 5mg/L.
Embodiment 21
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, thin beans cypress 5g/L, NaCl 5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 5mg/L.
Embodiment 22
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and thin beans cypress 5g/L, yeast soaks powder 5g/L, NaCl5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 10mg/L.
Embodiment 23
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and dextrin 60g/L, thin beans cypress 30g/L, soybean protein 60g/L, yeast soaks powder 5g/L, NaCl 5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 35mg/L.
Embodiment 24
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and wheat starch 40g/L, cottonseed meal 60g/L, soybean protein 20g/L, yeast soaks powder 5g/L, NaCl 5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 30mg/L.
Embodiment 25
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and wheat starch 40g/L, dextrin 60g/L, thin beans cypress 35g/L, soybean protein 60g/L, yeast soaks powder 5g/L, NaCl 5g/L.Automatically controlled fermentation temperature is 30 ℃, pH6.5, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 40mg/L.
Embodiment 26
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and thin beans cypress 30g/L, soybean protein 20g/L, yeast soaks powder 10g/L, NaCl 1g/L.Automatically controlled fermentation temperature is 20 ℃, pH5.0, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 45mg/L.
Embodiment 27
By 1 seed making 1% (v/v) inoculum size in embodiment, be inoculated in fermention medium, ferment.Fermention medium forms: glucose 40g/L, and thin beans cypress 30g/L, soybean protein 20g/L, yeast soaks powder 1g/L, NaCl 10g/L.Automatically controlled fermentation temperature is 40 ℃, pH8.0, and dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 72h, the output of pentostatin reaches 35mg/L.
Comparative example 1
Get antibiosis streptomycete (Streptomyces antibioticus) NRRL3238 of embodiment 1, use the seed of embodiment 1, by fermentation culture method described in patent US3923785, concrete fermention medium is 2% glucose, 2% soybean cake powder, 0.5%NaCl, 0.25%CaCO
3, before sterilization, with NaOH, adjust PH to 7.5.37 ℃ of leavening temperatures, dissolved oxygen is 40%, air flow 0.5VVM, 24h starts stream and adds glucose 1～10 ‰ L/h.Fermentation period 120h, the output of pentostatin is 2mg/L.
Claims (8)
1. for a fermention medium for antibiosis streptomycete (Streptomyces antibioticus) fermentative production pentostatin, described fermention medium comprises by the gross weight of substratum:
0.5～14% carbon source, described carbon source is selected from one or more in glucose, dextrin and wheat starch;
0.5～10% thin bean cake powder, soybean protein, soybean cake powder and/or cotton seed powder cake;
0.1～1% yeast soaks powder; With
0.1～1%NaCl。
2. fermention medium as claimed in claim 1, is characterized in that, described fermention medium also further contains trace somatomedin.
3. fermention medium as claimed in claim 1, is characterized in that, described fermention medium also contains defoamer.
4. a fermentation method for producing for pentostatin, is characterized in that, comprises step:
(a) seed liquor of antibiosis streptomycete (Streptomyces antibioticus) is inoculated in fermention medium and carries out liquid fermentation and culture, described fermention medium is fermention medium claimed in claim 1;
(b) from fermented liquid, isolate pentostatin.
5. method as claimed in claim 4, is characterized in that, in step (a), the seed liquor of described antibiosis streptomycete method is routinely cultivated antibiosis streptomycete to obtain in seed culture medium.
6. method as claimed in claim 4, is characterized in that, in step (a), described antibiosis streptomycete is antibiosis streptomycete NRRL3238.
7. method as claimed in claim 4, is characterized in that, in step (a), the temperature of described fermentation culture is 20～40 ℃.
8. method as claimed in claim 4, is characterized in that, in step (a), the pH value of described fermentation culture is 5～8.
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| CN106701788B (en) * | 2016-12-20 | 2019-10-25 | 武汉大学 | Pentostatin and arabinosy ladenosine biological synthesis gene cluster and its application |
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|---|---|---|---|---|
| US3923785A (en) * | 1974-04-22 | 1975-12-02 | Parke Davis & Co | (R)-3-(2-deoxy-{62 -D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo{8 4,5-d{9 {8 1,3{9 diazepin-8-ol |
| CN101463332A (en) * | 2007-12-17 | 2009-06-24 | 郭崇华 | Antibiosis streptomycete |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3923785A (en) * | 1974-04-22 | 1975-12-02 | Parke Davis & Co | (R)-3-(2-deoxy-{62 -D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo{8 4,5-d{9 {8 1,3{9 diazepin-8-ol |
| CN101463332A (en) * | 2007-12-17 | 2009-06-24 | 郭崇华 | Antibiosis streptomycete |
Non-Patent Citations (2)
| Title |
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| 一株抗青枯假单胞菌放线菌的筛选、鉴定及发酵条件优化;雷娟等;《应用与环境生物学报》;第16卷(第01期);79-83 * |
| 雷娟等.一株抗青枯假单胞菌放线菌的筛选、鉴定及发酵条件优化.《应用与环境生物学报》.第16卷(第01期),79-83. |
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