CN105803015A - Method for converting dicentrine into (4S,6aR)-4-hydroxyl dicentrine through Clonostachys sp. Fermentation - Google Patents
Method for converting dicentrine into (4S,6aR)-4-hydroxyl dicentrine through Clonostachys sp. Fermentation Download PDFInfo
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Abstract
The invention discloses a method for converting dicentrine into (4S,6aR)-4-hydroxyl dicentrine through Clonostachys sp.fermentation and particularly provides a method for completely converting the dicentrine into the (4S,6aR)-4-hydroxyl dicentrine in the mode that traditional Chinese medicinal materials and a compound are converted through microbial fermentation, namely, the traditional Chinese medicinal materials are not compatible with the compound dicentrine through the Clonostachys sp.fermentation, supersonic extraction is performed through an appropriate solvent, filtration and concentration are performed, then a large amount of produced (4S,6aR)-4-hydroxyl dicentrine can be detected by combining a TLC thin-layer chromatography and a high-performance liquid chromatography. The (4S,6aR)-4-hydroxyl dicentrine has the anti-tumor activity the same as the activity of the dicentrine, but the water solubility is improved by near 1800 times. The method converting a large amount of dicentrine into the (4S,6aR)-4-hydroxyl dicentrine through the Clonostachys sp.fermentation is efficient, innovative, mild in reaction condition, green and pollution-free, is easily produced in an expanded mode and adopts simple operating devices.
Description
Technical field
The present invention relates to microorganism and convert plant chemical ingredient field, establish one specifically and pass through plant
Dicentrine in pathogenic fungi Clonostachys sp. modification Radix Stephaniae Epigaeae converts (4S, 6aR)-4-hydroxyl in a large number
The method of dicentrine, to improve water solublity and the derivatization probability of dicentrine.
Background technology:
Radix Stephaniae Epigaeae (Stephania epigaea Lo) Menispermaceae (Menispermaceae) Stephania (Stephania
Lour.) plant, is distributed mainly on the west and south and the southeast in Yunnan, is grown on the limestone in damp and hot river valley,
Popular name Stephania cepharatha Hayata, Herba Sonerilae cantonensis, Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae) etc..Belonging to Stephania Stephania cepharatha Hayata subgenus in Plant Taxonomy, resource is relatively
Horn of plenty.Originate in Eastern Yunnan, middle part and western part, western Sichuan and south.Often it is born in tor, the most common cultivation
Training.Its tuber is the Chinese traditional herbs that Yunnan is famous, bitter in the mouth and pungent, cool in nature, slightly poisonous, function heat-clearing and toxic substances removing,
Calm, regulate the flow of vital energy, pain relieving.Medical value and the economic worth of this plant are the biggest, it is necessary to it is carried out chemistry one-tenth
Point and pharmacology in terms of research. clinical trial shows, the content of Radix Stephaniae Epigaeae total alkaloids and the proportional pass of its curative effect
System.
Before over thousands of year, fermentable is applied to Chinese medicine processing by China.Medicine after clean system or process
Thing, at a certain temperature and humidity conditions, utilizes the catalyticing decomposition action of the enzyme that Institute of Micro-biology secretes, makes medicine
Thing foaming, raw clothing.Chinese medicine reaches to improve herbal medicine efficacy, change the property of medicine, reduction toxic and side effects by the fermentation process of preparing Chinese medicine
Etc. purpose.
Dicentrine class belongs to isoquinoline alkaloid, and people are to the Study on Physiological Activity of this compounds always
The most active.Dicentrine has analgesia, calm, anticancer and intestinal smooth spasmolysis；Have been reported
Dicentrine has certain increasing to people's GLC cell, people's uterus carcinoma HeLa cell and KB cell
Grow inhibitory action.But its water solublity is poor, druggability probability is low, and derivatization probability is low.Therefore, I
Need to improve the probability of its water solublity and derivatization.4-hydroxyl dicentrine has and dicentrine phase
The anti-tumor activity of same level, but its water-soluble be nearly 1800 times of dicentrine.Therefore, invention one turns
Change the method that dicentrine is 4-hydroxyl dicentrine the most important.
In recent years, because the growth of microorganism cycle is short, avoid because condition acutely produces unnecessary side reaction
Feature and the advantage such as microorganism conversion reaction conditions is gentle, by-product is few, stereo selectivity is strong, utilize micro-
The method of biological (fungus, antibacterial and algae) fermentation modification is increasingly subject to people's attention.Raw in reality
In product, substantial amounts of application example has been had to be produced by the fermentation of microorganism some novelties, active higher
And to the useful food of health or medicine etc..
Summary of the invention
It is contemplated that converted in tradition by plant pathogenic fungi Clonostachys sp. solid and liquid fermentation
The dicentrine of medical material Radix Stephaniae Epigaeae, thus reach Efficient Conversion dicentrine purpose, the invention provides one
Planting conversion ratio high, equipment requirements is low, simple and easy to operate, green non-pollution, is suitable for industrialization and converts Dicentra spectabilis
Alkali is the method for (4S, 6aR)-4-hydroxyl dicentrine.
Another object of the present invention is to utilize plant pathogenic fungi Clonostachys sp. to come by solid and liquid
Body microbe conversion Radix Stephaniae Epigaeae, thus reached Efficient Conversion dicentrine for (4S, 6aR)-4-hydroxyl Dicentra spectabilis
Alkali effect.Method is simple for this kind, low for equipment requirements, green non-pollution, is that one is highly suitable for work
The method that industry metaplasia is produced.
It is an object of the invention to by the realization of technical scheme in detail below: a kind of by Clonostachys sp.
Microbe conversion dicentrine is the method for (4S, 6aR)-4-hydroxyl dicentrine, it is characterised in that solid fermentation
Radix Stephaniae Epigaeae converts and carries out as follows:
(1) first plan Microbial biomass C lonostachys sp. is activated, will connect by Clonostachys sp.
Plant after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivate 3-7d
After, it is placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) after taking dry Radix Stephaniae Epigaeae pulverizing medicinal materials, take appropriate medicinal powder and be placed in conical flask, add
After tap water infiltration, observe the wettability of medical material；Will be equipped with the conical flask of medical material packaging of jumping a queue and be placed on 121 DEG C
Sterilizing 30min in high-temperature sterilization box, cools down medical material after taking-up；
(4) seed culture medium of step (2) is inoculated in an aseptic environment through step (3) pre-treatment
Radix Stephaniae Epigaeae on, packaging of jumping a queue be placed in incubator cultivation 5-30d after take out.
(5) through Microbial biomass C lonostachys sp. ferment before and after Radix Stephaniae Epigaeae through methanol solution supersound extraction,
Filter and be concentrated to give crude extract；It is individually separated dicentrine and (4S, 6aR)-4-hydroxyl lotus that crude extract obtains
The structural formula of bag bicuculline is as follows:
(6) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column to enter
Row separates, and separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
To compound on gel column purification, pass through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains
Compound structure；
The described response time is 5-30d.
Described in the described response time, reaction temperature is 20-37 DEG C.
Described Extraction solvent is methanol.
A kind of is (4S, 6aR)-4-hydroxyl Dicentra spectabilis by Clonostachys sp. microbe conversion dicentrine
The method of alkali, it is characterised in that liquid fermentation dicentrine converts and carries out as follows:
(1) first plan Microbial biomass C lonostachys sp. is activated, will Clonostachys sp.
It is inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivates 3-7
After d, it is placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) dicentrine is dissolved in methanol, joins in the seed culture medium of (2), in constant-temperature table
Take out after middle cultivation 3-15d.
(4) through Microbial biomass C lonostachys sp. ferment after Radix Stephaniae Epigaeae through ethyl acetate solution supersound extraction,
Filter and be concentrated to give crude extract；Separate the structure of (4S, 6aR)-4-hydroxyl dicentrine that crude extract obtains
Formula is as follows:
(5) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column to enter
Row separates, and separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
To compound on gel column purification, pass through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains
Compound structure.
The described response time is 3-15d.
Described in the described response time, reaction temperature is 20-37 DEG C.
Described Extraction solvent is ethyl acetate.
Using fermentable Radix Stephaniae Epigaeae of the present invention to convert dicentrine is (4S, 6aR)-4-hydroxyl dicentrine
Method, compared with prior art, the preparation method advantage of the present invention is:
(1) the most perhaps dicentrine is raw material, and a step catalytic reaction can be converted into
(4S, 6aR)-4-hydroxyl dicentrine；
(2) selecting microbial enzyme is catalyst, and its essence is protein, has strong regioselectivity, vertical
Body selectivity and the specificity of height, and catalytic reaction condition is gentle, it is not necessary to the participation of chemical reagent and
The conditions such as the High Temperature High Pressure of chemical reaction.
In sum, the raw material Radix Stephaniae Epigaeae that this inventive method uses is cheap and easily-available, and Dicentra spectabilis alkali content is higher,
Reaction condition is gentle, be easily controlled, environmental nonpollution, and equipment requirements is simple, the conversion produced of suitably magnifying
Dicentrine is the process of (4S, 6aR)-4-hydroxyl dicentrine.
Accompanying drawing explanation
Fig. 1 is target compound in the present invention1H-NMR；
Fig. 2 is target compound in the present invention13C-NMR；
Detailed description of the invention
The present invention is expanded on further below in conjunction with embodiment, but the present invention is not limited to this specific embodiment, ability
Field technique personnel it should be appreciated that present invention encompasses in right all possible alternative,
Improvement project and equivalents.
1. converted by solid fermentation:
(1) first plan Microbial biomass C lonostachys sp. is activated, will Clonostachys sp.
It is inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivates 3-7
After d, it is placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) after taking dry Radix Stephaniae Epigaeae pulverizing medicinal materials, take appropriate medicinal powder and be placed in conical flask, add
After tap water infiltration, observe the wettability of medical material；Will be equipped with the conical flask of medical material packaging of jumping a queue and be placed on 121 DEG C
Sterilizing 30min in high-temperature sterilization box, cools down medical material after taking-up；
(4) seed culture medium of step (2) is inoculated in an aseptic environment through step (3) pre-treatment
Radix Stephaniae Epigaeae on, packaging of jumping a queue be placed in incubator cultivation 5-30d after take out.
(5) through Microbial biomass C lonostachys sp. ferment before and after Radix Stephaniae Epigaeae through methanol solution supersound extraction,
Filter and be concentrated to give crude extract；It is individually separated dicentrine and (4S, 6aR)-4-hydroxyl lotus that crude extract obtains
The structural formula of bag bicuculline is as follows:
(6) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column to enter
Row separates, and separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
To compound on gel column purification, pass through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains
Compound structure.
2. converted by liquid fermentation:
(1) first plan Microbial biomass C lonostachys sp. is activated, will Clonostachys sp.
It is inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivates 3-7
After d, it is placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) dicentrine is dissolved in methanol, joins in the seed culture medium of (2), in constant-temperature table
Take out after cultivating 3-15d.
(4) through Microbial biomass C lonostachys sp. ferment after Radix Stephaniae Epigaeae through ethyl acetate solution supersound extraction,
Filter and be concentrated to give crude extract；Separate the structure of (4S, 6aR)-4-hydroxyl dicentrine that crude extract obtains
Formula is as follows:
(5) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column to enter
Row separates, and separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
To compound on gel column purification, pass through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains
Compound structure.
Up to the present, the method is a kind of efficient, novelty, reaction condition gentleness, green without dirty
Dye, easily extension produces, and it is (4S, 6aR)-4-hydroxyl that operation equipment converts dicentrine the most in a large number
The method of dicentrine, not only meets modern environment protection and the demand of low-carbon economy, and be the later stage Ah
Solid foundation has been established in the research and development further of Piao Fei alkaloid.
Embodiment 1
(1) Microbial biomass C lonostachys sp. bought from Kunming Xin Zhiling Science and Technology Ltd. in May, 2014,
Radix Stephaniae Epigaeae was bought from Bellamya quadrata gulf, Kunming Chinese Medicinal Materials Markets in November, 2014.
(2) first plan Microbial biomass C lonostachys sp. is activated, will Clonostachys sp.
It is inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivates 3-7
After d, it is placed in 4 DEG C of refrigerators；
(3) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 7d；
(4) after taking dry Radix Stephaniae Epigaeae pulverizing medicinal materials, take appropriate medicinal powder and be placed in conical flask, add
After tap water infiltration, observe the wettability of medical material；Will be equipped with the conical flask of medical material packaging of jumping a queue and be placed on 121 DEG C
Sterilizing 30min in high-temperature sterilization box, cools down medical material after taking-up；
(5) seed culture medium of step (2) is inoculated in an aseptic environment through step (3) pre-treatment
Radix Stephaniae Epigaeae on, packaging of jumping a queue be placed in incubator cultivation 5-30d after take out.
(6) through Microbial biomass C lonostachys sp. ferment before and after Radix Stephaniae Epigaeae through methanol solution supersound extraction,
Filter and be concentrated to give crude extract；It is individually separated dicentrine and (4S, 6aR)-4-hydroxyl lotus that crude extract obtains
The structural formula of bag bicuculline is as follows:
(7) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column
Separating, separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
On the compound obtained, gel column purification, passes through1H-NMR,13C-NMR and HR-ESI-MS identifies
To compound structure.
Result shows: Radix Stephaniae Epigaeae medical material is after Clonostachys sp. ferments, and the composition of its compound is sent out really
Give birth to change.Contain dicentrine the most in a large number, under the effect of Clonostachys sp., be changed into
(4S, 6aR)-4-hydroxyl dicentrine.TLC and HPLC checks, dicentrine and (4S, 6aR)-4-hydroxyl
Dicentrine achieves the conversion of 1:1 substantially, and this result does not find in research before.Cause
This, it completely can be as a kind of efficient, Green-pollution, low for equipment requirements conversion dicentrine
For the method for (4S, 6aR)-4-hydroxyl dicentrine, for after us, Dicentra spectabilis alkali derivant is entered one
Step research provides favourable condition.
It is white that the previous research of this laboratory shows that the method utilizing plant pathogenic fungi to ferment can be effectively improved
And and the total phenol content of little Pseudobulbus Bletillae (Rhizoma Bletillae) and antioxidant activity, the process of preparing Chinese medicine for Chinese medicine material provides a kind of new think of
Road.Additionally, fermentable can modify some chemical compositions efficiently, such as steroidal, alkaloid, saponin,
Phenolic compounds etc., not only save the production cost in building-up process, and avoid the use of chemical reagent,
Can yet be regarded as a kind of efficient, easy mode of production meeting Modern Green Chemistry and sustainable development chemistry.
Conversion ratio of the present invention is high, and green non-pollution is simple and easy to do, the high conversion conversion that reaction condition is gentle
Dicentrine is that (4S, 6aR)-4-hydroxyl dicentrine shows: (4S, 6aR)-4-hydroxyl dicentrine and
Precursor compound realizes equivalent and converts, and conversion ratio is close to 100%, and after conversion, water solublity improves nearly 1800
Times, and anti-tumor activity keeps the level of dicentrine substantially.
Embodiment 2
(1) Microbial biomass C lonostachys sp. bought from Kunming Xin Zhiling Science and Technology Ltd. in May, 2014,
Radix Stephaniae Epigaeae was bought from Bellamya quadrata gulf, Kunming Chinese Medicinal Materials Markets in November, 2014.
(2) first Microbial biomass C lonostachys sp. is activated, then Clonostachys sp. is inoculated
To after the PDA slant medium that 121 DEG C of high temperature sterilizes process, in constant incubator, cultivate 3-7d
After, it is placed in 4 DEG C of refrigerators；
(3) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(4) dicentrine is dissolved in methanol, joins in the seed culture medium of (2), in constant-temperature table
Take out after cultivating 3-15d.
(5) through Microbial biomass C lonostachys sp. ferment after Radix Stephaniae Epigaeae through ethyl acetate solution supersound extraction,
Filter and be concentrated to give crude extract；Separate the structure of (4S, 6aR)-4-hydroxyl dicentrine that crude extract obtains
Formula is as follows:
(6) detect through TLC thin layer chromatography, compare with crude drug respectively.It is then passed through silicagel column
Separating, separation process uses gradient elution, and eluant is chloroform: methanol (20:1), the most separated
On the compound obtained, gel column purification, passes through1H-NMR,13C-NMR and HR-ESI-MS identifies
To compound structure.
Result shows: dicentrine medical material is after Clonostachys sp. ferments, and the composition of its compound is true
There occurs change in fact.Contain dicentrine the most in a large number, under the effect of Clonostachys sp., be changed into
(4S, 6aR)-4-hydroxyl dicentrine.TLC and HPLC checks, dicentrine and (4S, 6aR)-4-hydroxyl
Dicentrine achieves the conversion of 1:1 substantially, and this result does not find in research before.Cause
This, it completely can be as a kind of efficient, Green-pollution, low for equipment requirements conversion dicentrine
For the method for (4S, 6aR)-4-hydroxyl dicentrine, for after us, Dicentra spectabilis alkali derivant is entered one
Step research provides favourable condition.
It is white that the previous research of this laboratory shows that the method utilizing plant pathogenic fungi to ferment can be effectively improved
And and the total phenol content of little Pseudobulbus Bletillae (Rhizoma Bletillae) and antioxidant activity, the process of preparing Chinese medicine for Chinese medicine material provides a kind of new think of
Road.Additionally, fermentable can modify some chemical compositions efficiently, such as steroidal, alkaloid, saponin,
Phenolic compounds etc., not only save the production cost in building-up process, and avoid the use of chemical reagent,
Can yet be regarded as a kind of efficient, easy mode of production meeting Modern Green Chemistry and sustainable development chemistry.
Conversion ratio of the present invention is high, and green non-pollution is simple and easy to do, the high conversion conversion that reaction condition is gentle
Dicentrine is that (4S, 6aR)-4-hydroxyl dicentrine shows: (4S, 6aR)-4-hydroxyl dicentrine and
Precursor compound realizes equivalent and converts, and conversion ratio is close to 100%.And water solublity improves nearly 1800 after converting
Times, and anti-tumor activity keeps the level of dicentrine substantially.
Claims (8)
1. pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine, it is characterised in that solid fermentation Radix Stephaniae Epigaeae converts and carries out as follows:
(1) first plan Microbial biomass C lonostachys sp. is activated, will be inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process by Clonostachys sp., after cultivating 3-7d in constant incubator, be placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) after taking dry Radix Stephaniae Epigaeae pulverizing medicinal materials, take appropriate medicinal powder and be placed in conical flask, after adding tap water infiltration, observe the wettability of medical material；Will be equipped with the conical flask of medical material packaging of jumping a queue and be placed on sterilizing 30min in 121 DEG C of high-temperature sterilization boxes, after taking-up, medical material is cooled down；
(4) being inoculated in an aseptic environment on the Radix Stephaniae Epigaeae of step (3) pre-treatment by the seed culture medium of step (2), packaging of jumping a queue is taken out after being placed in incubator cultivation 5-30d.
(5) through Microbial biomass C lonostachys sp. ferment before and after Radix Stephaniae Epigaeae through methanol solution supersound extraction, filter and be concentrated to give crude extract；The structural formula being individually separated dicentrine that crude extract obtains and (4S, 6aR)-4-hydroxyl dicentrine is as follows:
(6) detect through TLC thin layer chromatography, compare with crude drug respectively.Being then passed through silicagel column to separate, separation process uses gradient elution, and eluant is chloroform: methanol (20:1), on the compound being then isolated to, gel column purification, passes through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains compound structure.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 1, it is characterised in that the described response time is 5-30d.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 1, it is characterised in that described in the described response time, reaction temperature is 20-37 DEG C.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 1, it is characterised in that described Extraction solvent is methanol.
5. pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine, it is characterised in that liquid fermentation dicentrine converts and carries out as follows:
(1) first plan Microbial biomass C lonostachys sp. is activated, will be inoculated into after the PDA slant medium that 121 DEG C of high temperature sterilizes process by Clonostachys sp., after cultivating 3-7d in constant incubator, be placed in 4 DEG C of refrigerators；
(2) strain of activation is received in PDB seed culture medium, in constant-temperature table, cultivate 3-7d；
(3) dicentrine is dissolved in methanol, joins in the seed culture medium of (2), take out after cultivating 3-15d in constant-temperature table.
(4) through Microbial biomass C lonostachys sp. ferment after Radix Stephaniae Epigaeae through ethyl acetate solution supersound extraction, filter and be concentrated to give crude extract；The structural formula separating (4S, 6aR)-4-hydroxyl dicentrine that crude extract obtains is as follows:
(5) detect through TLC thin layer chromatography, compare with crude drug respectively.Being then passed through silicagel column to separate, separation process uses gradient elution, and eluant is chloroform: methanol (20:1), on the compound being then isolated to, gel column purification, passes through1H-NMR,13C-NMR and HR-ESI-MS identifies and obtains compound structure.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 5, it is characterised in that the described response time is 3-15d.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 5, it is characterised in that described in the described response time, reaction temperature is 20-37 DEG C.
Pass through the method that Clonostachys sp. microbe conversion dicentrine is (4S, 6aR)-4-hydroxyl dicentrine the most according to claim 5, it is characterised in that described Extraction solvent is ethyl acetate.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106636259A (en) * | 2016-11-07 | 2017-05-10 | 云南大学 | Method for producing antibiotics TMC-154 from microorganism Clonostachys rogersoniana by means of solid fermentation |
| CN107384983A (en) * | 2017-07-21 | 2017-11-24 | 云南大学 | Method and the application of ILLIGERA AROMATTICA prepare compound are handled by the mould solid fermentation of the asexual fringe of Rogers |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100999714A (en) * | 2006-12-18 | 2007-07-18 | 云南省微生物研究所 | Fusarium |
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| CN106636259A (en) * | 2016-11-07 | 2017-05-10 | 云南大学 | Method for producing antibiotics TMC-154 from microorganism Clonostachys rogersoniana by means of solid fermentation |
| CN106636259B (en) * | 2016-11-07 | 2020-02-18 | 云南大学 | A method for producing antibiotic TMC-154 by solid fermentation of microorganism Clonostachys rogesoniana |
| CN107384983A (en) * | 2017-07-21 | 2017-11-24 | 云南大学 | Method and the application of ILLIGERA AROMATTICA prepare compound are handled by the mould solid fermentation of the asexual fringe of Rogers |
| CN107384983B (en) * | 2017-07-21 | 2020-07-07 | 云南大学 | Method for preparing compound by processing moldavica robusta solid fermentation and application |
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