CN104877910A - Plant endophytic fungus Eupenicillium brefeldianum F4a and its application - Google Patents
Plant endophytic fungus Eupenicillium brefeldianum F4a and its application Download PDFInfo
- Publication number
- CN104877910A CN104877910A CN201410072690.1A CN201410072690A CN104877910A CN 104877910 A CN104877910 A CN 104877910A CN 201410072690 A CN201410072690 A CN 201410072690A CN 104877910 A CN104877910 A CN 104877910A
- Authority
- CN
- China
- Prior art keywords
- mine
- brefeldin
- bfa
- plant endogenesis
- bacterium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention relates to the technical field of microbes, and concretely relates to a new plant endophytic fungus and its application in the preparation of brefeldin A (BFA). The plant endophytic fungus is Eupenicillium brefeldianum F4a, and is preserved in China Center for Type Culture Collection on Dec. 18, 2012 with the preservation number of CCTCC M2012531. The Eupenicillium brefeldianum F4a can generate high content BFA, and the highest fermentation output reaches 1.9g/L. The invention also provides a method for preparing the highly pure BFA through HP20 solid phase extraction and rapid silica gel column chromatography or a pure crystallization technology. The method has the advantages of low production cost, great reduction of treatment and pollution of organic matters, and good industrial prospect. The BFA prepared in the invention has antifungal and insecticidal activity, and is an ideal veterinary or agricultural candidate drug.
Description
Technical field
The present invention relates to microbial technology field, be specially a kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a and application thereof.
Background technology
Endophyte of plant refers to that a class survives in health plant organization internal in its part or all of life history, and does not make host plant show the microorganism of obvious infection symptoms (at least temporarily not having infection symptoms).In long-term evolutionary process, define the relation of specific mutualism with this its special habitats of host, its growth metabolism is by the restriction of the many factors such as host, the external environment factor.Nowadays, the important physiology that endophyte plays and Ecology Action and the huge applications potentiality in agriculture, forestry and field of medicaments thereof, become the focus of research both at home and abroad gradually.Therefore, rich and varied endophyte of plant has become at the important sources finding antitumor, anti-infective and anti-plant pest active substance.The invention provides the plant endogenesis epiphyte mine-laying penicillium bacterium F4a that a strain is new, there is very strong antibacterial and insecticidal activity, the brefeldin A (brefeldin A, BFA) of generation high-content and it can ferment
BFA to be separated first by Singleton etc. as far back as 1958 and to obtain and be named as ducumbin. until Weber in 1971 etc. determine the absolute configuration of this compound from penicillium decumbens (Penicillium decumbens), and used brefeldin A as its title.Thus this title is used till today.BFA is a kind of macrolide antibiotics comprising 13 rings, and its uncompetitive inhibitor protein can be transported to golgi body from endoplasmic reticulum, therefore has the extensively biologic activity such as antimycotic, antitumor, antiviral, nematicide.The research of National Cancer research institute finds that BFA has Selective depression and kills human tumor cells activity.BFA is not by relying on p53 Apoptosis mechanism induction Human Prostate Cancer Cells apoptosis, and therefore, BFA is the apoptotic effective alternative chemotherapeutics not relying on p53 as induction.The conbined usage low dosage BFA such as Akira improve gemcitabine (gemcitabine) and the action effect to human pancreatic cancer cell MIA PaCa-2 cell line.This compound visible alternatively antitumor drug, medicine and pesticide intermediate and important molecular tool reagent has the larger market requirement.
BFA structural formula is as follows:
bFA is because its multifarious biological activity and unique chemical structure cause the interest at synthetic chemistry door.But because it contains mulitiple chiral centers, therefore chemosynthesis more complicated and yield is lower.Simultaneously, can ferment due to many fungies and produce BFA, comprise Cladosporium (Cladosporium), Phoma (Phoma), paecilomyces (Paecilomyces), Phyllosticta (Phyllosticta), Penicillium (Penicillium), Eupenicillium sp (Eupenicillium), Aspergillus (Aspergillus) etc.Therefore fermentable produces BFA becomes a kind of efficient manner.But the output of the fermentable product BFA of report is lower at present.It is 300mg/L that the United States Patent (USP) U.S.3896002 invented as Howard etc. discloses the ferment output of BFA of Phyllosticta medicaginis.It is 151.6mg/L that Liu Wanyun reports that Penicillium notatum Penicillium sp.SHZK-15 produces BFA after optimization of fermentation conditions.The Chinese patent CN101445784A of contriver Zheng Yu state etc. discloses the Eupenicillium brefeldianum variety ZJB 082702 utilizing low energy ion beam implantation technology mutagenic obtained and to ferment the BFA produced up to 943.8mg/L.Wang second places in 2012 etc. are optimized the fermentation condition of Eupenicillium brefeldianum variety ZJB 082702 further, finally make the output of BFA reach 1304.7mg/L.
Summary of the invention
The object of the invention is to provide a kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a and application thereof.
To achieve these goals, the technical solution used in the present invention is:
A kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a, plant endogenesis epiphyte is mine-laying penicillium bacterium F4a(Eupenicillium brefeldianum F4a), China typical culture collection center is preserved in, deposit number: CCTCC M2012531 on December 18th, 2012.
The application of plant endogenesis epiphyte mine-laying penicillium bacterium F4a, its feature: utilize described plant endogenesis epiphyte mine-laying penicillium bacterium F4a in order to prepare brefeldin A.
Plant endogenesis epiphyte mine-laying penicillium bacterium F4a is utilized to prepare the method for brefeldin A,
1) mine-laying penicillium bacterium F4a fermentation seed liquid is inoculated in PSB fermention medium according to volume ratio 1:10-1:20, cultivates 7-15d for 28 DEG C;
2) above-mentioned gained fermented liquid is adopted 4-6 layer filtered through gauze, solid-liquid separation obtains supernatant liquor and mycelium; Filtering supernatant adopts HP20 macroporous adsorbent resin Solid-Phase Extraction, obtains crude extract with 70-100% ethanol elution; Mycelium obtains extract through acetone extraction; Refine through MeOH further after merging two portions extract concentrating under reduced pressure and obtain the crude extract of BFA content more than 50-65%;
3) above-mentioned crude extract decompression flash silica gel chromatography is separated, using 49:1-0:10(v/v) methylene chloride/methanol solvent systems carries out gradient elution, collected volume per-cent is the methylene chloride/methanol elutriant of 47:3-44:6, obtains the brefeldin A that purity is 90-99%;
Or, by described crude extract by acetone solution, spend the night under normal temperature, obtain the brefeldin A that purity is 90-99%.
Bacterial strain F4a method of scoring is inoculated on PSA substratum by described step 1), in 28 DEG C of constant temperature culture 4-6d; Then adopt and dig block method and be inoculated in the 250mL triangular flask that 50mL PSB substratum is housed, cultivate 72h as fermentation seed liquid in 28 DEG C of 180rpm constant-temperature tables.
Described compound can be used for the anti-mycotic agent being prepared into medical, for animals or agricultural non-treatment object.
Described compound can be used for being prepared into sterilant.
Described compound can be used as the fungistat of Candida albicans, dry thread Pyrenomycetes, sickle-like bacteria.
Described compound can be prepared as and kill the agent of halogen worm.
The advantage that the present invention has: plant endogenesis epiphyte mine-laying penicillium bacterium F4a of the present invention, it has very strong antibacterial and insecticidal action, and it can ferment and produce the BFA of content up to more than 1.9g/L.Bacterial strain of the present invention produces the highest wild-type strain of BFA.Use fermentation medium components simple in the present invention and product is more single, simple and Extraction and isolation efficiently can be realized.Namely resin is utilized to adopt Solid-Phase Extraction and flash chromatography on silica gel or pure crystallization technique can obtain highly purified BFA.The method production cost is low, and greatly reduces organic process and pollution.This invention has good industrial prospect.
Accompanying drawing explanation
The morphological feature of the mine-laying penicillium bacterium F4a that Fig. 1 provides for the embodiment of the present invention.
The systematic evolution tree that the mine-laying penicillium bacterium F4a that Fig. 2 provides for the embodiment of the present invention builds based on its ITS gene order.
The ESIMS figure of the compound brefeldin A that Fig. 3 provides for the embodiment of the present invention.
The compound brefeldin A's that Fig. 4 provides for the embodiment of the present invention
1h-NMR (Bruker AV600, CD
3oD) spectrogram.
The compound brefeldin A's that Fig. 5 provides for the embodiment of the present invention
13h-NMR (Bruker AV600, CD
3oD) spectrogram
The X-ray single crystal diffraction result of the compound brefeldin A that Fig. 6 provides for the embodiment of the present invention.
The time curve of the mine-laying penicillium bacterium F4a fermentation product brefeldin A that Fig. 7 provides for the embodiment of the present invention.
Embodiment
Content for a better understanding of the present invention, is described further below in conjunction with specific embodiment, but the protection content of this patent is not limited only to this.
The qualification of embodiment 1 endophyte of plant mine-laying penicillium bacterium F4a
Plant endogenesis epiphyte F4a, China typical culture collection center is preserved on December 18th, 2012, depositary institution address is China. Wuhan. and Wuhan University, deposit number: CCTCC M2012531, taxonomy called after mine-laying penicillium bacterium F4a(Eupenicillium brefeldianum F4a).
Bacterial strain F4a is well-grown on PDA, Ma Dingshi substratum; Early stage bacterium colony is pure white, and bacterium colony central authorities become yellow-green colour gradually; Bacterium colony surface is fine hair shape, without transudate and soluble pigment; After ripe, bacterium colony has radial ridges, and central authorities swell a little, forms the obvious circular bacterial plaque of color, and the back side is in yellow.Microscopic observation, top is without the top capsule expanded, and its conidium structure is rare, and spore and is born in conidiophore, and in broom shape, stigma apical meristem spore becomes string-like, the subsphaeroidal or pyriform of conidium, size 2.5-2.0 × 2.2-1.6 μm (Fig. 1).
After bacterial strain F4a liquid culture 48h, extract STb gene, purified rear employing universal primer carries out the pcr amplification of ITS gene order, and PCR primer after testing, check order after purifying, obtain ITS sequence and submit GenBank database to, obtain the gene number of logging in: KF682223.BLAST compare of analysis result show, bacterial strain F4a and Eupenicillium brefeldianum A1163 homology the highest, reach 100%.F4a and Eupenicillium brefeldianum A1163 and Eupenicillium brefeldianum NRRL710 is in same branch (Fig. 2) for the display of phylogenetic analysis result.Comprehensive morphological feature, is accredited as Eupenicillium brefeldianum by F4a.
>F4a ITS
TTTATCGTACCTTGTTGCTTCGGCGGGCCCGCCGTTCCGGCCGCCGGGGGGCATCCGCCCCCGGGCCCGCGCCCGCCGAAGACACCATTGAACGCTGTCTGAAGAATGCAGTCTGAGCGATTAGCTAAATCAGTTAAAACTTTCAACAACGGATCTCTTGGTTCCGGCATCGATGAAGAACGCAGCGAAATGCGATAAGTAATGTGAATTGCAGAATTCAGTGAATCATCGAGTCTTTGAACGCACATTGCGCCCCCTGGTATTCCGGGGGGCATGCCTGTCCGAGCGTCATTGCTGCCCTCAAGCACGGCTTGTGTGTTGGGCCCCGCCCCCCGGCTACCGGGGGGCGGGCCCGAAAGGCAGCGGCGGCACCGCGTCCGGTCCTCGAGCGTATGGGGCTTCGTCACCCGCTCTGTAGGCCCGGCCGGCGCCCGCCGGCGACCCCCCTCAATCTTTCTCAGGTTGACCTCGGATCAGGTAGGGATACCCGCTGAACTTAAGCATATCAA
Embodiment 2 bacterial strain F4a fermentation is for BFA
The preparation of 2.1 seed liquor: first bacterial strain F4a method of scoring is inoculated on ready PSA culture medium flat plate, 28 DEG C of constant temperature culture 5d; Then mycelial growth place punch tool cut-off footpath 5mm bacterium block on flat board, is inoculated in 250mL triangular flask and is equipped with in 50mL PSB substratum, and 28 DEG C of 180rpm constant-temperature tables cultivate 72h;
Described PSB substratum is: 20.0g sucrose sugar, 200g potato leach liquor, with distilled water trim to 1L, pH5.0 ~ 8.0, and 115 DEG C of sterilizing 30min.
PSA is then the solid medium that often liter of PSB adds 18g agar.
2.2 large bottles fermentations: be the triangular flask of 3L with capacity, every bottled PSB substratum 0.70L, for subsequent use after 115 DEG C of sterilizing 30min.Every bottle graft kind seed liquor 50mL, 28 DEG C of 180rpm constant-temperature tables cultivate 7-13d, and ferment 10L altogether;
The acquisition of 2.3 crude extracts: fermented liquid will be obtained and adopt 4-6 layer filtered through gauze, and complete solid-liquid separation.Filtering supernatant adopts HP20 macroporous adsorbent resin Solid-Phase Extraction, 15% ethanol elution removal of impurities, and 100% ethanol elution obtains 6.09g crude extract A; Mycelium obtains 13.23g extract B through acetone extraction more than 3 times.Merge the extract after two portions concentrating under reduced pressure, and add pure MeOH solution 200-250mL, ultrasonic 10-20min makes it dissolve completely as far as possible, then static more than 10min, draw supernatant liquor refining for MeOH to another round-bottomed flask after solid-liquid separation, concentrating under reduced pressure obtains BFA content more than 50% crude extract 11.5g.
The purifying of 2.4BFA and preparation:
First the ratio that above-mentioned crude extract and silica gel mass ratio are about 1:2 mixes sample, and underpressure distillation is to complete drying.Get out 500-600 order column chromatography silica gel post simultaneously.After completing dry method loading, carry out gradient elution purifying (v/v49:1-0:10) according to methylene chloride/methanol system.Collected volume, than the elution fraction under methylene chloride-methanol (v/v) wash-out for 45:5, obtains purity and surpasses 90%BFA5.729g.Or 2.3 gained crude extracts are about 50mg through acetone ultrasonic dissolution, and room temperature hold over night solvent flashing can separate out the BFA crystal 28mg of purity more than 95%.
The structure elucidation of embodiment 3BFA
BFA is clear crystal, ESI-MS provides (Fig. 3) m/z303.2 [M+Na]
+(Calcd.for C
16h
24o
4na, 303.1572) infer that its molecular formula is C
16h
24o
4.?
1h-NMR(600MHz, CD
3oD) in spectrum (table 1 and Fig. 4), low place δ
h7.46(1H, dd, J=15.5,2.2Hz) and 5.82(1H, d, J=15.5Hz) form a trans double bond, and one end is connected on quaternary carbon; δ
h5.27(H, dd, J=15.1,9.7Hz) and 5.77(1H, ddd, J=15.1,9.7,4.4Hz) form another trans double bond, two ends connect CH and CH respectively
2group.Hydrogen δ on 3 company's oxygen carbon
h4.04(1H, brd, J=9.1Hz), 4.80(1H, m) and 4.21(1H, m) and 1 methyl proton signal δ be connected on CH
h1.24(3H, d, J=6.2Hz).
13c-NMR(150MHz, CD
3oD) 16 carbon signals (table 1 and Fig. 5) are provided in, wherein 1 ester carbonyl group carbon signal δ
c166.96; 4 unsaturated carbon signal δ
c153.69,136.70,129.99,116.37; 3 company oxygen sp
3the carbon δ of hydridization
c75.21,71.8,71.56; 1 methyl carbon signal δ
c19.66.In conjunction with calculating its degree of unsaturation be 5, remove 1 carbonyl and 2 pairs of double bonds, compound should be twin nuclei.To sum up can infer that this compound should for having 2 pairs of trans double bond, 2 hydroxyls, 1 methyl, 1 methoxyl group and having α, the dicyclo macrolide of beta unsaturated ketone.In conjunction with its ESI-MS can the two dimensional structure of preliminary deterministic compound identical with BFA.
Because this compound has 5 chiral centres, X-Ray single crystal diffraction is therefore adopted to measure its relative configuration further.The unit cell parameters of this chemical combination single crystal diffraction is respectively:
spacer is P212121, and derivation crystalline structure as shown in Figure 6.Finally measuring the specific rotation of this compound, obtaining its specific rotatory power by calculating
+ 95.4 ± 2.0(c1.40, MeOH).Therefore finally determine that its absolute configuration is for (1R, 2E, 6S, 10E, 11aS, 13S, 14aR)-1,13-dihydroxy-6-methyl-6,7,8,9,12,13,14,14a-octahydro-H-cyclopenta [f] [1] oxacyclotridecin-4 (11aH)-one.Namely this compound is BFA.Its NMR signals assignment is as shown in table 1.
The NMR signals assignment of table 1.Brefeldin A and feature (CD
3oD)
Embodiment 4 fungi F4a produces the output of BFA
The content of HPLC quantitative analysis fungi F4a different time fermented supernatant fluid BFA in HP20 Solid-Phase Extraction thing and thalline methanol extract.Utilize Dionex U3000HPLC system Criterion curve, use C18YMC-Pack ODS-A (5 μm, φ 4.6 × 250mm) post, elution program is: initial solvent is methyl alcohol: water (7:3), be pure methyl alcohol during linear gradient wash-out 20min, flow velocity 0.53ml/min, determined wavelength 210nm.
Quantitative analysis results shows, and BFA produces from during fermentation 2d, and increases gradually.In initialization phase fermented liquid, content is higher than in thalline, but in fermentation 7 days later fermented liquids, content reduces gradually and tends towards stability.And in thalline, content rises gradually along with the growth of fermentation time, and reach peak value when 13d.Fermented liquid output when 7d is the highest, reach 509.1mg/L, and thalline is the highest when 13d, is equivalent to thalline output in 1L fermented liquid up to 1605.5mg.Brefeldin A output when amounting to its 13d in fermented liquid and thalline is up to 1939.6mg/L(Fig. 7).This is the bacterial strain that the current product brefeldin A reported is the highest.
The bioactive mensuration of embodiment 5BFA
Paper-agar block diffusion experiment (paper-agar disk diffusion assay) is adopted to determine the inhibit activities of compd B FA to pathogenic fungi and bacterium.
For filamentous fungus, first beat 9mm bacterium block by after dry thread Pyrenomycetes and cucumber fusarium axysporum activation with punch tool, be inoculated into the dull and stereotyped central authorities of PSA, 28 DEG C of constant temperature culture, when colony growth is greater than 4cm to diameter, the BFA of purifying is mixed with the methanol solution that concentration is respectively 2mg/mL.Anti-mycotic activity is measured with filter paper enzyme, applied sample amount is 20 μ L, filter paper diameter is 8mm, Deng the complete follow-up diameter recording inhibition zone when 28 DEG C of constant temperature culture to pathogenic fungies grow to and are paved with whole flat board that continues of methyl alcohol volatilization on filter paper, antibacterial circle diameter is larger, illustrates that antimycotic activity of this bacterial strain is stronger.
Experimental result shows, BFA Rhizoctonia solani and cucumber fusarium axysporum all show good anti-mycotic activity, and antibacterial circle diameter is respectively 18mm and 6.4mm.Therefore BFA has the application prospect used as disinfectant use in agriculture.
For Candida albicans, intestinal bacteria and subtilis, then first by above-mentioned target bacterium activation, and be configured to 2-5 × 10 with the physiological saline of sterilizing
4the concentration of cfu/ml, gets 50ul and is spread evenly across on substratum.Then by pre-prepd 2mg/mL BFA solution, measure anti-mycotic activity with filter paper enzyme, applied sample amount is 20 μ L, and filter paper diameter is 8mm, continues 28 DEG C of constant temperature culture 48h.Inhibit activities result display BFA does not show inhibit activities to intestinal bacteria and subtilis, and demonstrates extremely strong inhibit activities to Candida albicans, and its antibacterial circle diameter reaches 22mm.
Halogen worm bioassay method (Brine Shrimp Assay, BSA) is adopted to evaluate the insecticidal activity of BFA.Concrete operations: the artificial seawater first being prepared by above-described embodiment the sterilizing of gained compound is mixed with the aqueous solution that final concentration is respectively 200,100,50,25,12.5,6.23 μ g/ml, be added in 96 hole polystyrene plates of sterilizing respectively according to every hole 100 μ l, each concentration three repetition.With the artificial seawater of sterilizing for blank.Then added in each 96 orifice plates by the halogen worm liquid of having hatched in advance, make halogen borer population in every hole be 10-20, volume is 200 μ l.Room temperature places 24h, observes with binocular anatomical lens, record halogen worm death toll.Concentration during death that halogen worm is whole is decided to be the minimum of this compound and kills concentration.Result shows, BFA shows stronger insecticidal activity, and it is 100 μ g/ml to the minimum concentration of killing of halogen worm.
Claims (8)
1. a plant endogenesis epiphyte mine-laying penicillium bacterium F4a, it is characterized in that: plant endogenesis epiphyte is mine-laying penicillium bacterium F4a(Eupenicillium brefeldianum F4a), China typical culture collection center is preserved in, deposit number: CCTCC M2012531 on December 18th, 2012.
2. an application of plant endogenesis epiphyte mine-laying penicillium bacterium F4a according to claim 1, its feature: utilize described plant endogenesis epiphyte mine-laying penicillium bacterium F4a in order to prepare brefeldin A.
3. the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 1, is characterized in that:
1) mine-laying penicillium bacterium F4a fermentation seed liquid is inoculated in PSB fermention medium according to volume ratio 1:10-1:20, cultivates 7-15d for 28 DEG C;
2) above-mentioned gained fermented liquid is adopted 4-6 layer filtered through gauze, solid-liquid separation obtains supernatant liquor and mycelium; Filtering supernatant adopts HP20 macroporous adsorbent resin Solid-Phase Extraction, obtains crude extract with 70-100% ethanol elution; Mycelium obtains extract through acetone extraction; Refine through MeOH further after merging two portions extract concentrating under reduced pressure and obtain the crude extract of BFA content more than 50-65%;
3) above-mentioned crude extract decompression flash silica gel chromatography is separated, using 49:1-0:10(v/v) methylene chloride/methanol solvent systems carries out gradient elution, collected volume per-cent is the methylene chloride/methanol elutriant of 47:3-44:6, obtains the brefeldin A that purity is 90-99%;
Or, by described crude extract by acetone solution, spend the night under normal temperature, obtain the brefeldin A that purity is 90-99%.
4., by the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 3, it is characterized in that:
Bacterial strain F4a method of scoring is inoculated on PSA substratum by described step 1), in 28 DEG C of constant temperature culture 4-6d; Then adopt and dig block method and be inoculated in the 250mL triangular flask that 50mL PSB substratum is housed, cultivate 72h as fermentation seed liquid in 28 DEG C of 180rpm constant-temperature tables.
5., by the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 3, it is characterized in that: described compound can be used for being prepared into the anti-mycotic agent of medical, for animals or agricultural non-treatment object.
6., by the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 3, it is characterized in that: described compound can be used for being prepared into sterilant.
7., by the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 5, it is characterized in that: described compound can be used as the fungistat of Candida albicans, dry thread Pyrenomycetes, sickle-like bacteria.
8., by the method utilizing plant endogenesis epiphyte mine-laying penicillium bacterium F4a to prepare brefeldin A according to claim 6, it is characterized in that: described compound can be prepared as and kill the agent of halogen worm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410072690.1A CN104877910B (en) | 2014-02-27 | 2014-02-27 | A kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410072690.1A CN104877910B (en) | 2014-02-27 | 2014-02-27 | A kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a and its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104877910A true CN104877910A (en) | 2015-09-02 |
| CN104877910B CN104877910B (en) | 2017-12-19 |
Family
ID=53945591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410072690.1A Active CN104877910B (en) | 2014-02-27 | 2014-02-27 | A kind of plant endogenesis epiphyte mine-laying penicillium bacterium F4a and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104877910B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827805A (en) * | 2017-06-05 | 2018-03-23 | 海南师范大学 | A kind of indoles diterpene-kind compound of mangrove xylocarpus granatum originated from fungus and preparation method and application |
| CN109111422A (en) * | 2017-06-23 | 2019-01-01 | 沈阳药科大学 | Macrolides compound and its application in preparation prevention and treatment plant-pathogenic pathogenic bacteria drug |
| CN113583881A (en) * | 2021-09-13 | 2021-11-02 | 福建省微生物研究所 | Penicillium strain for producing brefeldin A by fermentation and application thereof |
| CN113773287A (en) * | 2021-08-30 | 2021-12-10 | 中国科学院沈阳应用生态研究所 | Bioactive secondary metabolite and preparation and application thereof |
| CN114058516A (en) * | 2020-08-01 | 2022-02-18 | 中国海洋大学 | Marine-source brefeldin A-producing penicillium fungus N29 and application thereof |
| CN114874915A (en) * | 2022-01-24 | 2022-08-09 | 中国人民解放军陆军军医大学 | Corydalis mauritiana endophytic fungus for producing brefeldin A and application thereof |
| CN115074255A (en) * | 2022-06-24 | 2022-09-20 | 自然资源部第三海洋研究所 | Fusarium and application of fermentation compound thereof in preventing and treating necrosis apoptosis-related diseases |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4305249A1 (en) * | 1993-02-20 | 1994-08-25 | Hoechst Ag | Galactosylbrefeldin A, a metabolite with pharmacological action, a process for its preparation and its use |
| CN101445784A (en) * | 2008-12-31 | 2009-06-03 | 浙江工业大学 | Eupenicillium brefeldianum variety ZJB082702 and application thereof in preparation of Brefeldin A by fermentation |
| CN101580805A (en) * | 2009-03-31 | 2009-11-18 | 中国人民解放军第二军医大学 | Brefeldin A-producing bacteria and method for preparing brefeldin A by fermentation |
| CN102399210A (en) * | 2011-11-18 | 2012-04-04 | 浙江工业大学 | Method for separating and extracting high-purity brefeldin A from fermentation liquor |
-
2014
- 2014-02-27 CN CN201410072690.1A patent/CN104877910B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4305249A1 (en) * | 1993-02-20 | 1994-08-25 | Hoechst Ag | Galactosylbrefeldin A, a metabolite with pharmacological action, a process for its preparation and its use |
| CN101445784A (en) * | 2008-12-31 | 2009-06-03 | 浙江工业大学 | Eupenicillium brefeldianum variety ZJB082702 and application thereof in preparation of Brefeldin A by fermentation |
| CN101580805A (en) * | 2009-03-31 | 2009-11-18 | 中国人民解放军第二军医大学 | Brefeldin A-producing bacteria and method for preparing brefeldin A by fermentation |
| CN102399210A (en) * | 2011-11-18 | 2012-04-04 | 浙江工业大学 | Method for separating and extracting high-purity brefeldin A from fermentation liquor |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107827805A (en) * | 2017-06-05 | 2018-03-23 | 海南师范大学 | A kind of indoles diterpene-kind compound of mangrove xylocarpus granatum originated from fungus and preparation method and application |
| CN109111422A (en) * | 2017-06-23 | 2019-01-01 | 沈阳药科大学 | Macrolides compound and its application in preparation prevention and treatment plant-pathogenic pathogenic bacteria drug |
| CN114058516A (en) * | 2020-08-01 | 2022-02-18 | 中国海洋大学 | Marine-source brefeldin A-producing penicillium fungus N29 and application thereof |
| CN114058516B (en) * | 2020-08-01 | 2023-07-28 | 中国海洋大学 | Penicillium fungus N29 capable of producing brefeldin A from ocean source and application thereof |
| CN113773287A (en) * | 2021-08-30 | 2021-12-10 | 中国科学院沈阳应用生态研究所 | Bioactive secondary metabolite and preparation and application thereof |
| CN113583881A (en) * | 2021-09-13 | 2021-11-02 | 福建省微生物研究所 | Penicillium strain for producing brefeldin A by fermentation and application thereof |
| CN114874915A (en) * | 2022-01-24 | 2022-08-09 | 中国人民解放军陆军军医大学 | Corydalis mauritiana endophytic fungus for producing brefeldin A and application thereof |
| CN114874915B (en) * | 2022-01-24 | 2023-06-23 | 中国人民解放军陆军军医大学 | Cordycepin A-producing endophytic fungus and application thereof |
| CN115074255A (en) * | 2022-06-24 | 2022-09-20 | 自然资源部第三海洋研究所 | Fusarium and application of fermentation compound thereof in preventing and treating necrosis apoptosis-related diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104877910B (en) | 2017-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104877910A (en) | Plant endophytic fungus Eupenicillium brefeldianum F4a and its application | |
| CN108165500A (en) | One plant of marine fungi Aspergillus terreus C23-3, zymotic fluid activity extract and its preparation method and application | |
| CN103555607B (en) | A kind of endophyte H6 strain separation methods in silk tree blade and its application | |
| CN103360351B (en) | Isopimarane diterpenoid compounds and application thereof | |
| CN102482188A (en) | Novel anthraquinone derivatives | |
| CN110305798A (en) | The purposes of one plant of Aspergillus and the compound and application thereof prepared by the Aspergillus | |
| Biswas et al. | Endophytes producing podophyllotoxin from Podophyllum sp. and other plants: A review on isolation, extraction and bottlenecks | |
| CN104277982A (en) | Tricyclic sesquiterpenoid compound as well as preparation method and applications thereof | |
| CN102634551B (en) | Algal epiphytic fungus chlorinated depside cyclic ether compound, and preparation and application thereof | |
| CN102220247B (en) | Glycyrrhiza endophytic fungi for producing glycyrrhetic acid | |
| CN110218200B (en) | Cyclic depsipeptide compound in mangrove endophytic fungi and preparation method and application thereof | |
| CN107974412A (en) | A kind of penicillium roqueforti for being used to prepare antiinflammatory active compound peniroquesine A and its application | |
| CN109020861A (en) | The preparation method and application of compound pencolide | |
| CN114437011B (en) | Chromone compound and preparation method and application thereof | |
| CN109400444B (en) | Sesquiterpenoids for inhibiting plant pathogenic fungi and preparation method thereof | |
| CN102786528B (en) | Polyoxybiotic alkali compound as well as preparation method and application thereof | |
| CN102659547B (en) | Ophiobolin sesterterpene compound and preparation and application thereof | |
| CN108033877A (en) | A kind of anti-MRSA naphthalene compounds and preparation method thereof | |
| CN101857842B (en) | Metarhizium GYYA0601 strain capable of producing broad-spectrum antibiotics and application thereof | |
| Pandey | Lichens: a resource chest of herbal antimicrobial compounds | |
| CN112961783A (en) | Plant endophytic fungus and application thereof in preparation of spironolactone derivative | |
| CN102701935B (en) | Tetranuclear diterpenoids as well as preparation and application thereof | |
| CN101235040B (en) | Phomopsis rhzomorph compound and its preparation method and application | |
| CN104774773A (en) | Polygonum cuspidatum endogenous bacterial strain aspergillus fumigates J3 bacterial strain for converting polydatin | |
| CN108017528A (en) | A kind of naphthalene compounds and preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |