CN107236686A - A kind of dactylosporangium aurantiacum and its application in regulating microorganism metabolism thing feldamycin - Google Patents
A kind of dactylosporangium aurantiacum and its application in regulating microorganism metabolism thing feldamycin Download PDFInfo
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Abstract
The invention discloses a kind of dactylosporangium aurantiacum (Dactylosporangium aurantiacum) FID1307 and its application, the strain is by China typical culture collection center preservation, and preserving number is CCTCC NO：M2017311, preservation date is：On 06 07th, 2017.The invention also discloses a kind of method that thus strain fermentation prepares feldamycin.The zymotechnique that the present invention is provided is through big production practices, it was demonstrated that its fermentation stability, accessory substance are few, the difficulty extracted after greatly reducing, suitable industrialized production, and the feldamycin product quality obtained is high.
Description
Technical field
Applied the present invention relates to a kind of microorganism and its in pharmaceutical field, specifically dactylosporangium aurantiacum is by adjusting
Control the application that microbial metabolism obtains feldamycin.
Background technology
Feldamycin (fidaxomicin, trade name Dificid, former name OPT-80, PAR-101), is to have 18 yuan of rings
The macrolide antibiotics of structure, can be by dactylosporangium aurantiacum hamdenensis subspecies (Dactylosporangium
Aurantiacumsubspecie hamdenensis) ferment and obtain, it can specifically refer to sporangiocyst bacterium NRRL 18085 by actinomyces and produce
It is raw.The obtained product of dactylosporangium aurantiacum fermentation is family and feldamycin structure very close product, and referred to as platform hooks mycin
(tiacumicins) it is, different by structure, it is referred to as Tiacumicins A, B, C, D, E and F.Feldamycin hooks mould for the platform of R configurations
Plain B, with new mechanism of action (structural formula is as follows).
Feldamycin obtains U.S. FDA approval listing in May, 2011, and for treating clostridium difficile, (difficulty distinguishes fusiform gemma bar
Bacterium, Clostridium difficile) infection induced diarrhea (CDAD).This is the first treatment that FDA ratifies over nearly 30 years
CDAD medicine, European Union's in December, 2011 approval listing.
(the denomination of invention of Chinese patent literature 03818016.2：Platform hooks the preparation of mycin) disclose and prepare TCM B
Method, it is prepared to obtain in tunning, contain higher accessory substance, impurity (see accompanying drawing 1).
(the denomination of invention of Chinese patent literature 201310208223.2：A kind of Actinoplanes bacteria strain and its preparing non-reach
Application in mycin) disclose and shown in its HPLC analysis chart (see accompanying drawing 2) for preparing tunning, figure in tunning
Contain more accessory substance and impurity.
Those of ordinary skill in the art are known in the feldamycin tunning that prior art is prepared into containing more
Debris, accessory substance, the presence of these materials will bring very big difficulty to follow-up purification, for some purification link in very
The impurity that hardly possible is removed, will have a strong impact on the quality of final medicine.
The content of the invention
Regarding the issue above, the present invention provides the few feldamycin producing strains of a kind of fermentation stability, accessory substance,
Application of the bacterial strain in feldamycin is prepared, and specific fermentation preparation are provided simultaneously.
The purpose of the present invention is realized by following technical proposal：
A kind of dactylosporangium aurantiacum, Classification And Nomenclature is Dactylosporangium aurantiacum FID1307, in
State's Type Tissue Collection preservation (abbreviation CCTCC), preserving number is：CCTCC NO：M 2017311, preservation date is：
On June 7th, 2017.
Described preserving number is CCTCC NO：The colony characteristicses of M 2017311 bacterial strain：Bacterium colony subcircular, surfacing,
1~2mm of colony diameter, median rise, no secretion and soluble pigment are produced.
Described preserving number is CCTCC NO：The bacterial strains of M 2017311 can be applied to fermentation and prepare feldamycin.The preparation side
Method comprises the following steps：
A. bacterial strain uses deposit number for CCTCC NO：M 2017311 bacterial strain；
B. by the 30% glycerine mycelia cryovial prepared according to a conventional method, by the 3~5% of shake-flask seed culture medium volume
Inoculum concentration accesses shake-flask seed culture medium, and 220~260rpm cultivates 2~3 days, obtains shake-flask seed liquid；
The inoculum concentration that shake-flask seed liquid is accumulated into 0.1~0.2% by seed tank culture matrix is inoculated in seeding tank, 120~
200rpm, cultivates 3~4 days, obtains tank seed liquor；
Tank seed liquor is inoculated in fermentation tank culture medium by the inoculum concentration of fermentation tank culture medium volume 5~15%, 150~
200rpm, fermented and cultured 9~12 days collects the resin in zymotic fluid；
Wherein cultivation temperature is 26~30 DEG C.
The ratio of wherein described shake-flask seed culture medium each component in the medium is：In every 100mL culture mediums, carbon source
1~4.5g, 4~7.7g of nitrogen source, 0.1~0.4g of inorganic salts, remaining is water；
The ratio of seed tank culture base each component in the medium is：In every 100mL culture mediums, 1.5~6g of carbon source, nitrogen source
5~9g, 0.2~0.6g of inorganic salts, remaining is water；
The ratio of fermentation tank culture medium each component in the medium is：In every 100mL culture mediums, 4.5~10g of carbon source, nitrogen
1.7~5g of source, 0.8~1.8g of inorganic salts, 3~6g of resin, remaining is water；
Wherein described culture medium each component ratio in the medium, shake-flask seed culture medium is preferably in a proportion of：Per 100mL
In culture medium, 2~3g of carbon source, 5~7g of nitrogen source, 0.2~0.3g of inorganic salts, remaining is water；
Seed tank culture base each component being preferably in a proportion of in the medium：In every 100mL culture mediums, 2~4g of carbon source, nitrogen
6~8g of source, 0.3~0.5g of inorganic salts, remaining is water；
Fermentation tank culture medium each component being preferably in a proportion of in the medium：In every 100mL culture mediums, 5~8g of carbon source, nitrogen
2~4g of source, 0.8~1.2g of inorganic salts, 4~5g of resin, remaining is water.
Wherein described carbon source is selected from sucrose, glucose, oatmeal, D- xyloses, D-ribose, galactolipin, maltose, malt
One or more in dextrin, cornstarch, soluble starch, farina, corn dextrin, glycerine；Nitrogen source is selected from sour water
Solve casein, beef extract, yeast extract, yeast extract powder, malt and leach powder, dusty yeast, soy peptone, peptone, seitan
One or more in powder, cotton seed meal, soybean cake powder, corn starch, corn protein powder, urea；Inorganic salts be selected from citrate,
Potassium nitrate, CaCO3、K2HPO4、MnSO4.7H2O、NaCl、MgSO4.7H2O、FeSO4.7H2O、KH2PO4In one or more；Tree
Fat is selected from any of HZ818, PAD900, HB60.
Wherein described culture medium is preferably：Carbon source is the one or more in glucose, cornstarch；Nitrogen source is beef
Medicinal extract, dusty yeast, soybean cake powder, soy peptone, corn protein powder, the one or more of cotton seed meal；Inorganic salts are K2HPO4、
KH2PO4、CaCO3One or more；Resin is HZ818 or PAD900.
Preserving number of the present invention is CCTCC NO：M 2017311 bacterial strain is presently available for large-scale production
Bacterial strain.Fermentation process is the important step of feldamycin production, and its fermentation level is directly related with technique quality, and the present invention is provided
Zymotechnique by shake flask fermentation and the experiment of 10 tons of fermentation tanks, its stable production capacity.After testing, the bacterium provided with the present invention
Strain and fermented and cultured can obtain the higher feldamycin of fermentation titer, while fermentation byproduct is less, product component is single, homology
Thing miscellaneous peak is less, is detected through HPLC, feldamycin normalization content 40~43%.So as to be provided for follow-up industrialized production
Good basis, reduces the difficulty of subsequent extracted, so as to be conducive to the acquisition of the feldamycin of high-quality, in industrialized production
Application aspect there is very big advantage.
The zymotic fluid that the zymotic fluid prepared with the strain of the present invention is reported with Chinese patent literature is contrasted through HPLC, very
Substantially the zymotic fluid impurity of the present invention is few, and concentration of active substance is higher, is conducive to big production.
Bacterial strain preservation situation：Wuhan China typical culture collection center (abbreviation CCTCC) is preserved in, deposit number is
CCTCC NO：M 2017311.Preservation date is on June 7th, 2017.
Brief description of the drawings
Fig. 1 is the zymotic fluid HPLC figures in Chinese patent literature 03818016.2
Fig. 2 is the zymotic fluid HPLC figures in Chinese patent literature 201310208223.2
Fig. 3 schemes for the zymotic fluid HPLC of the embodiment of the present invention 2
Fig. 4 schemes for the zymotic fluid HPLC of the embodiment of the present invention 3
Fig. 5 schemes for the zymotic fluid HPLC of the embodiment of the present invention 4
Fig. 6 schemes for the zymotic fluid HPLC of the embodiment of the present invention 5
Embodiment
It is further described with reference to specific embodiment for the present invention, but can not be by method involved in scheme
And technical parameter is interpreted as limitation of the present invention.
Embodiment 1：Preserving number is CCTCC NO：The culture of the bacterial strains of M 2017311 and physiological and biochemical property and utilization of carbon source
Situation
1st, preserving number is CCTCC NO：The morphological feature of the strain culturings of M 2017311
It is CCTCC NO by preserving number：The inoculations of M 2017311 are in ISP2 (yeast extract malt leaches powder agar) culture
Base, 30 DEG C are cultivated 10~14 days, are observed the morphological feature of bacterium colony and are described.
Observation finds that the colony growth enriches, 14 days 1~2mm of diameter；Cultivate early stage bacterium colony subcircular, late stage of culture edge
Irregular projection, central concave；Mycelia orange of light color is to rose pink, and no secretion and soluble pigment are produced.
2nd, preserving number is CCTCC NO：The bacterial strain Physiology and biochemistry cultural characteristics of M 2017311
The cultural characteristic row of bacterial strain in the medium see the table below shown in 1.
The CCTCC NO of table 1：The strain culturing features of M 2017311
| Culture medium | Growing state | Lawn color | Soluble pigment |
| Isp2 yeast extracts malt leaches powder agar medium | +++ | Shallow orange | - |
| Isp3 oatmeal agar | ++ | It is pale pinkish grey | - |
| Isp4 inorganic salts-starch agar | ++ | It is shallow pale pinkish grey | - |
| Isp5 glycerine asparagine agar | +- | It is shallow pale pinkish grey | - |
| ISP6 peptones yeast extract soaks juice iron agar | ++ | It is light yellow | - |
| ISP7 tyrosine agars | +- | It is shallow pale pinkish grey | - |
+：Growth is general；++：Growth is medium；+++：Growth is abundant；—：Lack
Base silk is few in ISP2 culture mediums, short, irregular branch, no gas silk, is formed on the surface of some agar mediums
Dactylosporangium.
This time experiment culture medium based on peptone-phosphate, 30 DEG C of cultures, are periodically observed.As a result such as table 2 below
Shown, result of the test is shown, the bacterial strain can assimilate sucrose, glucose, maltose, D- xyloses, glycerine, galactolipin, D-ribose etc.,
D-R, mannose, rhamnose, D-Fructose, lactose, sorbose etc. can not be utilized.
The CCTCC NO of table 2：M 2017311 utilization of carbon source situation
| Carbon source | Growing state |
| Sucrose | + |
| Glucose | + |
| Maltose | + |
| D- xyloses | + |
| Glycerine | + |
| Galactolipin | + |
| D-ribose | + |
| Inositol | ± |
| Raffinose | ± |
| D-R | - |
| Rhamnose | - |
| Mannose | - |
| D-Fructose | - |
| Lactose | - |
| Sorbose | - |
+：Sun is utilized；-：The moon is not utilized；±：Weakly positive is uncertain
Embodiment 2：Fermented and cultured prepares feldamycin
Preserving number is used for CCTCC NO：M 2017311 bacterial strain.
1st, Spawn incubation and preservation
Solid medium：Glucose 1g, soluble starch 2g, yeast extract powder 1g, acid hydrolyzed casein 0.5g, agar
2g, adds water to 100mL, pH and adjusts 7.0.
Solid culture method：Inoculation is in culture medium slant, and 30 DEG C are cultivated 8~10 days.
After solid culture terminates, it is standby that 4~10 DEG C of refrigerations are placed on inclined-plane.
2nd, shake-flask seed culture
Culture medium：Glucose 1g, cornstarch 0.5g, farina 0.5g, dusty yeast 1g, soy peptone 1.5g,
Beef extract 2g, soybean cake powder 0.5g, CaCO30.4g, adds water to 100mL, pH7.0.
Liquid amount：100mL culture mediums, 121 DEG C of sterilizing 30min are filled in 500mL triangular flasks.
Inoculum concentration：5% (V/V) 30% glycerine mycelia cryovial
Cultivation temperature：30℃
Incubation time：3 days
Shaking speed：260rpm
Shake-flask seed cultural method：After 30% glycerine mycelia cryovial is thawed shaking flask kind is connect according to inoculum concentration 5% (V/V)
In sub- culture medium, treat that mycelia length rises, have obvious wall built-up phenomenon and bacterium it is dense be more than 12%, by 1L shake-flask seed nutrient solutions, access
In 1000L seeding tanks.
The making of 30% glycerine mycelia cryovial：Under aseptic conditions, the about 30mL of the glycerine after sterilizing is added and grown
Kind bottle in, shake up and about 30% glycerine hyphal suspension be made, then dispense into small test tube (5mL/ branch), place it is -20 DEG C low
Temperature refrigerator refrigeration is standby.
3rd, seeding tank seed culture medium
Seeding tank seed culture medium ratio and shake-flask seed culture medium ratio are consistent, add water to 500L, and pH adjusts 7.0.
Loading amount：1000L seeding tanks built-in culture medium 500L, 121 DEG C of sterilizing 30min.
Seed tank culture method：In cultured 1L shake-flask seed liquids access seeding tank, 30 DEG C, 4 days.Controlled in incubation
Tank pressure processed：0.04MPa, mixing speed 120rpm, throughput 1：1(V/V).
After culture, microscopy mycelia is sturdy, and dyeing is deep, no microbiological contamination, and bacterium is dense >=and 12%.
4th, fermentation tank culture
The ratio of fermentation medium each component in the medium is：1g containing glucose, maltose in per 100mL culture mediums
5g, cornstarch 4g, soybean cake powder 1.5g, yeast extract 2g, soy peptone 1.5g, potassium nitrate 0.5g, NaCl 0.1g, CaCO3
0.2g, HZ818 6g, bubble enemy 0.15%, remaining is water, pH7.0.
Loading amount：6 tons of the built-in culture medium of 10 tons of fermentation tanks
Fermentation tank culture method：On cultured 500L tanks in seed liquor access fermentation tank, 30 DEG C, 12 days.Incubation
Middle control tank pressure：0.04MPa, mixing speed 160rpm, throughput 1：1.3(V/V).
Fermentation termination judges：Mycelia dyeing is deep, and vacuole is more, and mycelia has fracture, autolysis.
Tank filtering is put, HZ818 is obtained, is soaked through conventional method, is detected, feldamycin HPLC normalization contents are 40%
(see accompanying drawing 3).
Embodiment 3：Fermented and cultured prepares feldamycin
(1) fermented and cultured feldamycin
Preserving number is used for CCTCC NO：M 2017311 bacterial strain.
Shake-flask seed culture：0.5g containing glucose, cornstarch 0.5g, soy peptone 5g, ferment in per 100mL culture mediums
Female powder 0.2g, beef extract 1.5g, soybean cake powder 1g, CaCO30.1g, remaining is water, and pH is natural.Access 5% (V/V's)
30% glycerine mycelia cryovial, 220rpm, 28 DEG C of cultures obtain seed liquor in 2 days.
Seed tank culture：0.5g containing glucose, dusty yeast 0.5g, cornstarch 1g, soybean protein in per 100mL culture mediums
Peptone 5g, beef extract 1.5%, cotton seed meal 1g, corn starch 1g, KH2PO40.5g, CaCO30.1g, remaining is water, and pH is natural.
Seed inoculum concentration 0.1% (V/V), 150rpm, 30 DEG C are cultivated 4 days.
Fermentation tank culture：1g containing glucose, maltodextrin 3g, dusty yeast 1g in per 100mL culture mediums, seitan powder 1g can
Soluble starch 4g, KH2PO40.3g, FeSO4.7H2O 0.2g, potassium nitrate 0.5g, HZ818 3g, bubble enemy 0.1%, CaCO3
0.1g, remaining is water, and pH is natural.Seed inoculum concentration 5% (V/V), 180rpm, 30 DEG C are cultivated 9 days.
Tank filtering is put, HZ818 is obtained, is soaked through conventional method, is detected, feldamycin HPLC normalization contents are 42%
(see accompanying drawing 4).
Embodiment 4：Fermented and cultured prepares feldamycin
(1) fermented and cultured feldamycin
Deposit number is used for CCTCC NO：M 2017311 bacterial strain
Shake-flask seed culture：1g containing sucrose, soluble starch 2g, soy peptone 0.5g, beef in per 100mL culture mediums
Medicinal extract 0.5g, malt leaches powder 2g, soybean cake powder 1g, CaCO30.2g, remaining is water, pH6.8.Access the 30% of 3% (V/V)
Glycerine mycelia cryovial, 250rpm, 28 DEG C, culture obtains seed liquor in 3 days.
Seed tank culture：1g containing sucrose, soluble starch 2g, soy peptone 1g, beef extract in per 100mL culture mediums
1g, malt leaches powder 2g, soybean cake powder 2g, CaCO30.2g, adds water to 500L, pH6.8.Seed inoculum concentration 0.2% (V/V),
180rpm, is cultivated 4 days by 26 DEG C.
Fermentation tank culture：It is beautiful per 100mL culture medium 2g containing glucose, maltodextrin 1g, dusty yeast 1g, cotton seed meal 0.5g
Rice starch 2g, K2HPO40.3g, FeSO4.7H2O 0.2g, urea 0.2g, sodium nitrate 0.5g, CaCO30.4g, HB60 4g, bubble enemy
0.15%, remaining is water, pH6.8.Seed inoculum concentration 8% (V/V), 150rpm, 26 DEG C are cultivated 10 days.
Put tank filtering, obtain HB60, soaked through conventional method, detect, feldamycin HPLC normalization content be 43% (see
Accompanying drawing 5).
Embodiment 5：Fermented and cultured prepares feldamycin
(1) fermented and cultured feldamycin
Deposit number is used for CCTCC NO：M 2017311 bacterial strain
Shake-flask seed culture：1.5g containing glucose, corn dextrin 3g, soy peptone 3g, soya bean in per 100mL culture mediums
Cake powder 2g, yeast extract 2g, CaCO30.3g, remaining is water, and pH is natural.5% (V/V) 30% glycerine mycelia cryovial is accessed,
240rpm, 30 DEG C of cultures obtain seed liquor in 2 days.
Seed tank culture：2.0g containing glucose, cornstarch 4g, dusty yeast 2g, corn protein powder in per 100mL culture mediums
3g, soybean cake powder 2g, yeast extract 1g, CaCO30.3g, remaining is water, and pH is natural.Seed inoculum concentration 0.1% (V/V), 200rpm,
28 DEG C are cultivated 3 days.
Fermentation tank culture：0.5g containing glycerine, maltodextrin 4g, dusty yeast 1g, corn protein powder in per 100mL culture mediums
3g, KH2PO40.5g, sodium nitrate 1g, MgSO4.7H2O 0.2g, MnSO4.7H2O 0.1g, PAD900 5g, bubble enemy 0.2%,
CaCO30.3g, remaining is water, pH7.0.Seed inoculum concentration 15% (V/V), 200rpm, 30 DEG C are cultivated 9 days.
Tank filtering is put, PAD900 is obtained, is soaked through conventional method, is detected, feldamycin HPLC normalization contents are 41%
(see accompanying drawing 6).
Claims (7)
1. a kind of dactylosporangium aurantiacum (Dactylosporangium aurantiacum) FID1307, by Chinese Typical Representative culture
Collection preservation, preserving number is CCTCC NO：M 2017311, preservation date is：On June 7th, 2017.
2. preserving number as claimed in claim 1 is CCTCC NO：M 2017311 bacterial strain is in fermentation prepares feldamycin
Using.
3. the preserving number as described in application claim 1 is CCTCC NO：M 2017311 strain fermentation is prepared in feldamycin
Method, it is characterised in that comprise the following steps：
A. fermentation strain uses deposit number for CCTCC NO：M 2017311 bacterial strain；
B. by the 30% glycerine mycelia cryovial prepared according to a conventional method, by 3~5% inoculation of shake-flask seed culture medium volume
Amount access shake-flask seed culture medium, 220~260rpm cultivates 2~3 days, obtains shake-flask seed liquid；
The inoculum concentration that shake-flask seed liquid is accumulated into 0.1~0.2% by seed tank culture matrix is inoculated in seeding tank, 120~200rpm,
Culture 3~4 days, obtains tank seed liquor；
Tank seed liquor is inoculated in fermentation tank culture medium by the inoculum concentration of fermentation tank culture medium volume 5~15%, 150~
200rpm, fermented and cultured 9~12 days collects the resin in zymotic fluid；
Wherein cultivation temperature is 26~30 DEG C.
4. fermentation preparation as claimed in claim 3, it is characterized in that：
The ratio of shake-flask seed culture medium each component in the medium is：In every 100mL culture mediums, 1~4.5g of carbon source, nitrogen source 4
~7.7g, 0.1~0.4g of inorganic salts, remaining is water；
The ratio of seed tank culture base each component in the medium is：In every 100mL culture mediums, 1.5~6g of carbon source, nitrogen source 5~
9g, 0.2~0.6g of inorganic salts, remaining is water；
The ratio of fermentation tank culture medium each component in the medium is：In every 100mL culture mediums, 4.5~10g of carbon source, nitrogen source 1.7
~5g, 0.8~1.8g of inorganic salts, 3~6g of resin, remaining is water.
5. fermentation preparation as claimed in claim 4, culture medium each component being preferably in a proportion of in the medium：
The ratio of shake-flask seed culture medium each component in the medium is：In every 100mL culture mediums, 2~3g of carbon source, nitrogen source 5~
7g, 0.2~0.3g of inorganic salts, remaining is water；
The ratio of seed tank culture base each component in the medium is：In every 100mL culture mediums, 2~4g of carbon source, 6~8g of nitrogen source,
0.3~0.5g of inorganic salts, remaining is water；
The ratio of fermentation tank culture medium each component in the medium is：In every 100mL culture mediums, 5~8g of carbon source, 2~4g of nitrogen source,
0.8~1.2g of inorganic salts, 4~5g of resin, remaining is water.
6. the preparation method as described in claim 4 or 5, wherein described culture medium each group is divided into：Carbon source is selected from sucrose, grape
Sugar, oatmeal, D- xyloses, D-ribose, galactolipin, maltose, maltodextrin, cornstarch, soluble starch, potato are formed sediment
One or more in powder, corn dextrin, glycerine；Nitrogen source is selected from acid hydrolyzed casein, beef extract, yeast extract, yeast and leached
Powder, malt leach powder, dusty yeast, soy peptone, peptone, seitan powder, cotton seed meal, soybean cake powder, corn starch, corn egg
One or more in white powder, urea；Inorganic salts are selected from citrate, potassium nitrate, CaCO3、K2HPO4、MnSO4.7H2O、NaCl、
MgSO4.7H2O、FeSO4.7H2O、KH2PO4In one or more；The one kind of resin in HZ818, PAD900, HB60.
7. preparation method as claimed in claim 6, wherein described culture medium is preferably：Carbon source is glucose, cornstarch
In one or more；Nitrogen source is beef extract, dusty yeast, soybean cake powder, soy peptone, corn protein powder, cotton seed meal
It is one or more of；Inorganic salts are K2HPO4、KH2PO4、CaCO3One or more；Resin is HZ818 or PAD900.
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| CN112111413A (en) * | 2020-09-27 | 2020-12-22 | 贵州省生物技术研究所(贵州省生物技术重点实验室、贵州省马铃薯研究所、贵州省食品加工研究所) | Trichoderma fermentation medium for antagonizing tea anthracnose pathogen and fermentation method |
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| WO2004014295A2 (en) * | 2002-07-29 | 2004-02-19 | Optimer Pharmaceuticals, Inc. | Tiacumicin production |
| CN102030791B (en) * | 2010-10-28 | 2013-01-23 | 中国科学院南海海洋研究所 | Four tiacumicin compounds as well as preparation methods and applications thereof in preparing antimicrobial agents |
| CN102115757B (en) * | 2010-12-14 | 2015-10-28 | 中国科学院南海海洋研究所 | Platform hooks biological synthesis gene cluster and the application thereof of mycin |
| CN102993251B (en) * | 2012-12-17 | 2016-03-16 | 苏州纳微科技有限公司 | A kind of method of high-efficient liquid phase chromatogram purification TCM B |
| CN103320355B (en) * | 2013-05-29 | 2014-09-24 | 华北制药集团新药研究开发有限责任公司 | Actinoplanessp. strain and its use in preparation of fidaxomicin |
| CN104846044B (en) * | 2014-02-17 | 2019-02-01 | 上海医药工业研究院 | A kind of fermentation medium improving feldamycin yield |
| CN104946708B (en) * | 2014-03-28 | 2018-06-12 | 上海医药工业研究院 | A kind of fermentation medium and fermentation process for producing feldamycin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112111413A (en) * | 2020-09-27 | 2020-12-22 | 贵州省生物技术研究所(贵州省生物技术重点实验室、贵州省马铃薯研究所、贵州省食品加工研究所) | Trichoderma fermentation medium for antagonizing tea anthracnose pathogen and fermentation method |
| CN112111413B (en) * | 2020-09-27 | 2023-08-08 | 贵州省生物技术研究所(贵州省生物技术重点实验室、贵州省马铃薯研究所、贵州省食品加工研究所) | Trichoderma fermentation medium for antagonizing tea anthracnose pathogen and fermentation method |
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Application publication date: 20171010 Assignee: Hangzhou Huadi Pharmaceutical Technology Co.,Ltd. Assignor: Hangzhou Huadong Medicine Group Biopharmaceutical Co.,Ltd. Contract record no.: X2021330000100 Denomination of invention: An orange finger sporangium and its application in regulating microbial metabolite fidamycin Granted publication date: 20191015 License type: Common License Record date: 20210820 |