CN101921721A - New marine Verrucosispora sp.FIM06031 and application thereof - Google Patents

New marine Verrucosispora sp.FIM06031 and application thereof Download PDF

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Publication number
CN101921721A
CN101921721A CN2010102426000A CN201010242600A CN101921721A CN 101921721 A CN101921721 A CN 101921721A CN 2010102426000 A CN2010102426000 A CN 2010102426000A CN 201010242600 A CN201010242600 A CN 201010242600A CN 101921721 A CN101921721 A CN 101921721A
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terpenoid
fim06031
wart spore
wart
verrucosispora
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江红
聂毅磊
林如
连云阳
郑卫
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Fujian Institute of Microbiology
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Abstract

The invention relates to a new marine Verrucosispora sp.FIM06031 and application thereof. In the invention, an actinomycete with high antineoplastic activity is separated and screened from the sponge; and the actinomycete is marine Verrucosispora sp.FIM06031. The invention also provides a method for extracting terpenoid FW03104, which has cell toxicant activity for tumor cells, from the Verrucosispora sp.FIM06031 fermentation liquid. The invention provides a lead compound for the research and development of new antineoplastic drugs, and has important value for developing and utilizing Chinese marine drug resources.

Description

A kind of new ocean wart spore bacteria strain and application thereof
[technical field]
The present invention relates to a kind of microorganism and application thereof, relate in particular to a kind of new ocean wart spore bacteria strain FIM06031 and use the anti-tumor activity lead compound FW03104 of its generation.
[background technology]
Wart spore Pseudomonas (Verrucosispora) is divided the earliest from marsh mud, belongs to actinomycetales Micromonosporaceae (Micromonosporaceae), gains the name because of spore surface has verruca, increase with incubation time, the wart of spore surface can become hair-like, and Gram-positive is not antiacid, strict aerobic, chemoheterotrophic bacteria, base silk is flourishing, branch have every, diameter 0.4 μ m produces single not zoospore.The wart spore Pseudomonas bacterial classification of having reported seldom, the bacterial classification major part comes from ocean, mangrove forest.The research report that derives from the secondary metabolite of wart spore Pseudomonas bacterial classification lacks.The German T ü bingen Bister of university in 2004 etc. have obtained many rings polyketide abyssomicinB~D of novel structure from wart spore bacterium AB-18-032 secondary metabolite, the wherein growth of abyssomicin C strongly inhibited gram-positive microorganism, even can suppress the growth of methicillin-resistant gold Portugal bacterium (MRSA).The German T ü bingen Fiedler of university in 2008 etc. find furan derivatives Proximicin A, B and the C of new antitumoral from wart spore bacterium MG-37.Proximicins structurally contains the amino furans of 4--2-carboxylic acid, is a kind of newfound gamma-amino acid.The Proximicins anti-microbial activity a little less than, but have very strong anti-tumor activity at gut epithelium tumour cell, mammary cancer, liver cancer, just be used as new anticancer drug candidate and in depth researching and developing.
[summary of the invention]
Technical problem to be solved by this invention is to provide a kind of new ocean wart spore bacteria strain FIM06031, this wart spore bacteria strain FIM06031 is preserved in China Committee for Culture Collection of Microorganisms common micro-organisms center on June 12nd, 2010, deposit number is CGMCC NO.3924, and obtains a kind of terpene lead compound that can suppress tumour by the fermented liquid of this new bacterial strain of extraction separation.
The present invention solves the problems of the technologies described above by the following technical programs:
This laboratory is separated to the tens strains actinomycetes that grow nonparasitically upon another plant altogether from the sponge in Ping Hai marine site, Putian, Fujian, the East Sea, and screens the good actinomycetes of a strain anti-tumor activity.By strain culturing feature, physio-biochemical characteristics and 16S rRNA genic system evolutionary analysis, it is accredited as the bacterial strain of wart spore Pseudomonas.
Further, be separated to a terpenoid FW03104 with the very strong novel structure of cytotoxic activity from the fermented liquid of this bacterial strain, the chemical structural formula of this terpenoid FW03104 is:
Figure BDA0000023993320000021
Further, this terpenoid FW03104 has following physical and chemical character:
(1) color and outward appearance: white amorphous powder;
(2) molecular formula: C 23H 32O 3
(3) high resolution electrospray ionization mass spectrum (HR-ESI-MS)
Observed value: m/z 379.2249[M+Na] +
Theoretical value: m/z 379.2351[M+Na] +
(4) 1The H NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ(ppm):4.54(dd),1.03,1.79,1.41,1.76,1.92(m),1.49,1.94,1.11,1.84,1.75(s),4.71(d),0.94(s),1.15(s),3.38(s),7.36,7.31,7.50;
(5) 13The C NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ(ppm):83.0,41.7,72.0,54.1,26.2,26.8,27.6,47.2,41.4,39.5,151.6,21.5,108.9,14.5,22.5,173.3,49.9,135.9,130.4,129.6,128.1;
(6) solubleness: be dissolved in methyl alcohol, acetone, acetonitrile, ethyl acetate and methyl-sulphoxide; Be slightly soluble in normal hexane and sherwood oil; Water insoluble.
Further, described terpenoid FW03104 preparation method's concrete steps are:
(1) fermented liquid of preparation wart spore bacterium FIM06031: at first a platinum loop wart spore bacterium FIM06031 starch asparagine agar slant culture is inserted seed culture medium, 35 ℃ of temperature, rotating speed 240rpm/min, incubation time 45h, change fermention medium over to by 10% culture transferring amount then, 28 ℃ of temperature, rotating speed 240rpm/min, shaking culture 96~120h;
(2) extract: will cultivate the wart spore bacterium FIM06031 bacterial strain fermentation liquor of gained by behind the centrifugal 15min of 4500rpm through step (1), the mycelia slag that obtains with 95% alcohol immersion of 2 times of volumes 2 times, the soak solution concentrating under reduced pressure, the ethyl acetate extraction of concentrated solution usefulness equivalent volumes 3 times, concentrating under reduced pressure gets medicinal extract shape extract;
(3) separate: the extract that step (2) is obtained adopts the purification on normal-phase silica gel column chromatography, with hexanaphthene: the acetone solvent gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Again through C 18Reversed phase column chromatography, with methyl alcohol: the water gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Through Sephadex LH-20 gel filtration chromatography, with the acetone wash-out, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104 again; Again through the purification on normal-phase silica gel column chromatography, with chloroform: the methanol solvate gradient elution, thin-layer chromatography detects, and obtains tumour cell is had the pure product of terpenoid FW03104 of cytotoxic activity.
Further, the component of described seed culture medium is: Zulkovsky starch 1.5%, glucose 0.5%, peptone 0.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, and NaCl 0.05%, (NH 4) 2SO 40.05%, CaCO 30.1%, 50% old seawater preparation, pH 7.5;
The component of fermention medium is: Zulkovsky starch 4%, glucose 0.5%, soybean cake powder 2.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, K 2HPO 40.05%, CaCO 30.1%, 50% old seawater preparation, pH7.8.
Beneficial effect of the present invention is: provide a kind of separation from the ocean of sponge wart spore bacteria strain FIM06031, and provide from this wart spore bacteria strain fermented liquid extraction separation to obtain the method for terpenoid FW03104, this terpenoid FW03104 has cytotoxic activity to tumour cell, this invention provides lead compound for researching and developing new antitumor drug, and the marine pharmaceutical resource that develops China is had important value.
[description of drawings]
The invention will be further described in conjunction with the embodiments with reference to the accompanying drawings.
Fig. 1 is the synoptic diagram based on the phylogenetic tree of 16S rRNA gene order of a kind of new ocean wart spore bacteria strain FIM06031 of the present invention and immediate type species.
Fig. 2 is the hydrogen nuclear magnetic resonance collection of illustrative plates of terpenoid FW03104 among the present invention.
Fig. 3 is the nuclear magnetic resonance of carbon collection of illustrative plates of terpenoid FW03104 among the present invention.
Fig. 4 is the relevant collection of illustrative plates of the heteronuclear multikey of terpenoid FW03104 among the present invention.
Fig. 5 is the relevant two-dimensional map of the hydrogen hydrogenation displacement study of terpenoid FW03104 among the present invention.
Fig. 6 is the single quantum coherent collection of illustrative plates of the heteronuclear of terpenoid FW03104 among the present invention.
Fig. 7 is the undistorted polarization transfer gain of the 135 degree collection of illustrative plates of terpenoid FW03104 among the present invention.
[embodiment]
A kind of new ocean wart spore bacteria strain FIM06031 of the present invention separates from the sponge in Ping Hai marine site, Putian, Fujian, the East Sea, screens and obtains by strain culturing feature, physio-biochemical characteristics and the evaluation of 16S rRNA genic system evolutionary analysis.In addition, extraction separation obtains a kind of pure product of terpenoid FW03104 that three kinds of tumour cell HepG2, EC109 and HeLa all had cytotoxic activity from this wart spore bacteria strain FIM06031 fermented liquid.
1. the separation of this bacterial strain FIM06031:
(1) 10 gram sponges (is not named, gather from Ping Hai marine site, Putian, Fujian, China East Sea in June, 2006) use sterile water wash 3 times, scissors subtracts broken, adds aseptic old seawater 30mL and grinds 3-5 minute in aseptic mortar, make the sponge suspension, get part sponge suspension and be diluted to 10 with Chen Haishui -1With 10 -2Doubly;
(2) get stoste respectively and the marine organisms sample suspension 0.1mL that diluted coats the starch asparagine and separates on the agar plate, dull and stereotypedly cultivate 7-20d down in 32 ℃;
(3) the above-mentioned separation agar plate of having cultivated of visual inspection, colonial morphology similar (bacterium colony circle, protuberance, little, smooth), bacterium colony is orange at the cultivation initial stage, with brown, the black of incubation time prolongation changing into, the single bacterium colony of picking actinomycetes is transferred in starch asparagine agar slant culture-medium, cultivates 10-15d down in 32 ℃, obtains 47 strain actinomycetes altogether, by bacterial strain anti-tumor activity primary dcreening operation, obtain the bacterial strain FIM06031 that a strain tunning has remarkable anti-tumor activity.
Wherein, the component of starch asparagine separation agar is: Zulkovsky starch 2%, L-asparagine 0.5%, KNO 30.1%, K 2HPO 43H 2O 0.05%, and NaCl 0.05%, MgSO 47H 2O 0.05%, CaCO 30.1%, K 2Cr 2O 70.005%, derosal (containing 50% benzimidazole) 0.1%, agar 1.5%, pH7.5;
The component of starch asparagine agar slant culture-medium is: Zulkovsky starch 2%, L-asparagine 0.05%, KNO 30.1%, K 2HPO 43H 2O 0.05%, and NaCl 0.05%, MgSO 47H 2O 0.05%, CaCO 30.1%, agar 1.8%, pH7.5.
2. the evaluation of this bacterial strain FIM06031:
(1) slant culture with bacterial strain FIM06031 lines Gao Shi asparagine agar plate oblique cutting cover glass in 32 ℃ of following cultivations 5-20 days, observes gas silk, Ji Si and pigment; Take out the cover glass observation by light microscope, electron microscope is observed spore shape and outward appearance down; The substratum that cultural characteristic and physio-biochemical characteristics adopt the plan of international chain mould to recommend is cultivated, is observed and describes; Bacterial strain FIM06031 spore single give birth on sporophore, spore surface has verruca; Spore is few on inorganic medium, well-grown on organic substratum, and all can grow at 20-40 ℃ (35 ℃ of optimum growth temperatures) do not grow more than 45 ℃; Can liquefy gelatin, solidify peptonized milk; Sucrose, maltose, starch, D-glucose, D-wood sugar and D-seminose etc. be can utilize, melibiose, rhamnosyl, raffinose, melizitose, D-fructose, sorbyl alcohol and inositol etc. do not utilized; Hydrocellulose not;
(2) bacterial strain FIM06031 genomic dna adopts enzymolysis process to extract, and the DNA sample that obtains is stored in-20 ℃, and this DNA sample is carried out the amplification of 16S rRNA gene PCR as dna profiling, and the PCR product send the order-checking of Beijing three rich companies; Existing sequence in the 16S rDNA sequence of measured bacterial strain and the GenBank database is compared, and carry out homology analysis; On LPSN (http://www.bacterio.cict.fr) website, choose corresponding type strain 16S rRNA gene order, phylogenetic analysis is compared with CLUSTAL-X software, the comparison file that generates carries out phylogenetic analysis with TREECON software adjacent method, and topological analysis is the result of 1000 repeated samplings; Found that bacterial strain FIM06031 and rare actinomycete wart spore Pseudomonas (Verrucosispora) deliver the type strain Verrucosispora gifhornensis DSM 44337 that comes into force THomology the highest, similarity 99.78% is up to 99.85% with wart spore bacterium Verrucosispora sp.AB-18-032 similarity;
Learn to sum up that (3) bacterial strain FIM06031 is the bacterial strain of wart spore Pseudomonas (Verrucosispora), names the sp.FIM06031 into Verrucosispora.In addition, the long 1375bp of 16S rRNA Gene Partial sequence of bacterial strain FIM06031 is EU696742 in DNA database GenBank accession number.Its phylogenetic tree is seen Fig. 1.
3. terpenoid FW03104 preparation method's concrete steps are:
(1) fermented liquid of preparation wart spore bacterium FIM06031: at first a platinum loop wart spore bacterium FIM06031 starch asparagine agar slant culture is inserted seed culture medium, 35 ℃ of temperature, rotating speed 240rpm/min, incubation time 45h, change fermention medium over to by 10% culture transferring amount then, 28 ℃ of temperature, rotating speed 240rpm/min, shaking culture 96~120h;
Wherein, the component of seed culture medium is: Zulkovsky starch 1.5%, glucose 0.5%, peptone 0.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, and NaCl 0.05%, (NH 4) 2SO 40.05%, CaCO 30.1%, the distilled water preparation, pH 7.5;
The component of fermention medium is: Zulkovsky starch 4%, glucose 0.5%, soybean cake powder 2.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, K 2HPO 40.05%, CaCO 30.1%, the distilled water preparation, pH 7.8;
(2) extract: will cultivate the wart spore bacterium FIM06031 bacterial strain fermentation liquor of gained by behind the centrifugal 15min of 4500rpm through step (1), the mycelia slag that obtains with 95% alcohol immersion of 2 times of volumes 2 times, the soak solution concentrating under reduced pressure, the ethyl acetate extraction of concentrated solution usefulness equivalent volumes 3 times, concentrating under reduced pressure gets medicinal extract shape extract;
(3) separate: the extract that step (2) is obtained adopts the purification on normal-phase silica gel column chromatography, with hexanaphthene: the acetone solvent gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Again through the C18 reversed phase column chromatography, with methyl alcohol: the water gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Through Sephadex LH-20 gel filtration chromatography, with the acetone wash-out, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104 again; Again through the purification on normal-phase silica gel column chromatography, with chloroform: the methanol solvate gradient elution, thin-layer chromatography detects, and obtains the pure product of terpenoid FW03104, and from the appearance, it is white amorphous powder.
4. the structure by MS and NMR technical evaluation terpenoid FW03104:
High resolution electrospray ionization mass spectrum (HR-ESI-MS)
Observed value: m/z 379.2249[M+Na] +
Theoretical value: m/z 379.2351[M+Na] +
1The H NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ (ppm): 4.54 (dd), 1.03,1.79,1.41,1.76,1.92 (m), 1.49,1.94,1.11,1.84,1.75 (s), 4.71 (d), 0.94 (s), 1.15 (s), 3.38 (s), 7.36,7.31,7.50 (see figure 2)s;
13The C NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ (ppm): 83.0,41.7,72.0,54.1,26.2,26.8,27.6,47.2,41.4,39.5,151.6,21.5,108.9,14.5,22.5,173.3,49.9,135.9,130.4,129.6,128.1 (see figure 3)s;
Simultaneously, the present invention has also measured the multiple nuclear magnetic resonance map of this compound (seeing Fig. 4 to Fig. 7), thereby determined carbon atom and the ownership of hydrogen atom and the chemical structure of this compound that this compound is all, determined that it is the terpenoid of novel structure, structural formula is as follows:
Figure BDA0000023993320000071
5. terpenoid FW03104 is carried out antitumor activity in vitro:
Present embodiment has carried out antitumor activity in vitro to terpenoid FW03104, shows that it has the effect of significant inhibition tumour.The test bacterial strain uses therefor is international tumor cell line, that is:
EC109 (esophageal cancer cell);
HepG2 (liver cancer cell);
HeLa (cervical cancer cell).
Embodiment: the tumour cell of taking the logarithm respectively vegetative period, use 0.25% tryptic digestion, transfer cell suspension density to 1 * 10 5~4 * 10 5Individual/mL, be inoculated in 96 orifice plates by 100 μ L/ holes, in 5%CO 2, cultivate 24h under 37 ℃ of conditions; Substratum in the culture hole is exhausted, every hole adds the nutrient solution that contains medicine of the respective concentration that 100 μ L have prepared, establish contrast and blank (contrast and blank per-cent preparation according to the methyl alcohol in the medicine of maximum concentration) simultaneously, this moment, the substratum serum-concentration was 2%, in 5%CO 2, continue to cultivate under 37 ℃ of conditions; Cultivating 24h, behind 48h and the 72h, take out corresponding orifice plate respectively, inverted microscope is observed down, and takes the aspect graph of cell; Every hole adds MTT liquid (5mg/ml) 10 μ L behind the 72h, continues to hatch 3-4h in incubator; The exhaustion nutrient solution, every hole adds the DMSO of 150 μ L, and it is dissolving crystallized to shake (about 10min) on decolorization swinging table; Select the 570nm wavelength, on enzyme-linked immunosorbent assay instrument, measure the absorbance value in each hole, the record result.Be calculated as follows medicine to inhibition rate of tumor cell:
Growth of tumour cell inhibiting rate (IC)=(OD control group-OD experimental group)/OD control group * 100%.
Tumour cell survival rate=OD experimental group/OD control group * 100%.
With SPSS software analysis median lethal concentration IC 50Test-results sees Table 1
Table 1FW03104 is to the restraining effect of tumour cell
Tumour cell HepG2 EC109 HeLa
IC 50(μM) 16.99 25.33 34.64
Terpenoid FW03104 can cause necrocytosis when high density, with the reduction of concentration, the restraining effect of growth of tumour cell is weakened.
Show from the anti tumor activity in vitro test of this terpenoid: it has very strong anti-tumor activity, thereby provides lead compound for researching and developing new antitumor drug, and the marine pharmaceutical resource that develops China is had important value.
In addition, the per-cent among the present invention in involved each nutrient media components is weight ratio, and in addition, other per-cent is volume ratio.

Claims (5)

1. new ocean wart spore bacteria strain, it is characterized in that: described ocean wart spore bacteria strain is wart spore bacterium FIM06031 (Verrucosispora sp.FIM06031), be preserved in China Committee for Culture Collection of Microorganisms common micro-organisms center on June 12nd, 2010, deposit number is CGMCC NO.3924.
2. terpenoid FW03104 who suppresses tumour is characterized in that: described terpenoid FW03104 is that the fermented liquid by separation and Extraction wart spore bacterium FIM06031 obtains, and the chemical structural formula of this terpenoid FW03104 is:
3. as the terpenoid FW03104 of inhibition tumour as described in the claim 2, it is characterized in that: it has following physical and chemical character:
(1) color and outward appearance: white amorphous powder;
(2) molecular formula: C 23H 32O 3
(3) high resolution electrospray ionization mass spectrum (HR-ESI-MS)
Observed value: m/z 379.2249[M+Na] +
Theoretical value: m/z 379.2351[M+Na] +
(4) 1The H NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ(ppm):4.54(dd),1.03,1.79,1.41,1.76,1.92(m),1.49,1.94,1.11,1.84,1.75(s),4.71(d),0.94(s),1.15(s),3.38(s),7.36,7.31,7.50;
(5) 13The C NMR (Nuclear Magnetic Resonance) spectrum (MEOD, 400MHz)
δ(ppm):83.0,41.7,72.0,54.1,26.2,26.8,27.6,47.2,41.4,39.5,151.6,21.5,108.9,14.5,22.5,173.3,49.9,135.9,130.4,129.6,128.1;
(6) solubleness: be dissolved in methyl alcohol, acetone, acetonitrile, ethyl acetate and methyl-sulphoxide; Be slightly soluble in normal hexane and sherwood oil; Water insoluble.
4. as the terpenoid FW03104 of inhibition tumour as described in the claim 2, it is characterized in that: the concrete steps of its preparation method are:
(1) fermented liquid of preparation wart spore bacterium FIM06031: at first a platinum loop wart spore bacterium FIM06031 starch asparagine agar slant culture is inserted seed culture medium, 35 ℃ of temperature, rotating speed 240rpm/min, incubation time 45h, change fermention medium over to by 10% culture transferring amount then, 28 ℃ of temperature, rotating speed 240rpm/min, shaking culture 96~120h;
(2) extract: will cultivate the wart spore bacterium FIM06031 bacterial strain fermentation liquor of gained by behind the centrifugal 15min of 4500rpm through step (1), the mycelia slag that obtains with 95% alcohol immersion of 2 times of volumes 2 times, the soak solution concentrating under reduced pressure, the ethyl acetate extraction of concentrated solution usefulness equivalent volumes 3 times, concentrating under reduced pressure gets medicinal extract shape extract;
(3) separate: the extract that step (2) is obtained adopts the purification on normal-phase silica gel column chromatography, with hexanaphthene: the acetone solvent gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Again through C 18Reversed phase column chromatography, with methyl alcohol: the water gradient elution, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104; Through Sephadex LH-20 gel filtration chromatography, with the acetone wash-out, thin-layer chromatography detects, and collects the stream part that contains terpenoid FW03104 again; Again through the purification on normal-phase silica gel column chromatography, with chloroform: the methanol solvate gradient elution, thin-layer chromatography detects, and obtains tumour cell is had the pure product of terpenoid FW03104 of cytotoxic activity.
5. as the terpenoid FW03104 of inhibition tumour as described in the claim 4, it is characterized in that:
The component of described seed culture medium is: Zulkovsky starch 1.5%, glucose 0.5%, peptone 0.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, and NaCl 0.05%, (NH 4) 2SO 40.05%, CaCO 30.1%, 50% old seawater preparation, pH 7.5;
The component of fermention medium is: Zulkovsky starch 4%, glucose 0.5%, soybean cake powder 2.5%, yeast powder 0.5%, MgSO 47H 2O 0.05%, K 2HPO 40.05%, CaCO 30.1%, 50% old seawater preparation, pH 7.8.
CN2010102426000A 2010-08-02 2010-08-02 New marine Verrucosispora sp.FIM06031 and application thereof Pending CN101921721A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110092758A (en) * 2019-03-27 2019-08-06 福建省微生物研究所 A kind of new bio alkali cpd and fermentation prepare the wart spore bacterial strain of the compound
WO2019227969A1 (en) * 2019-01-28 2019-12-05 中国科学院南海海洋研究所 Ansamycin all-carbon cycle polyketide-type antibiotic and uses thereof in preparing antimicrobial medications or anti-tumor medications
CN115109023A (en) * 2022-05-14 2022-09-27 福建省微生物研究所 Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019227969A1 (en) * 2019-01-28 2019-12-05 中国科学院南海海洋研究所 Ansamycin all-carbon cycle polyketide-type antibiotic and uses thereof in preparing antimicrobial medications or anti-tumor medications
CN110092758A (en) * 2019-03-27 2019-08-06 福建省微生物研究所 A kind of new bio alkali cpd and fermentation prepare the wart spore bacterial strain of the compound
CN110092758B (en) * 2019-03-27 2021-06-18 福建省微生物研究所 Novel alkaloid compound and wart spore strain for preparing compound by fermentation
CN115109023A (en) * 2022-05-14 2022-09-27 福建省微生物研究所 Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof
CN115109023B (en) * 2022-05-14 2023-10-27 福建省微生物研究所 Macrolide compound FWYZ52-A, fermentation strain, fermentation method and application thereof

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Application publication date: 20101222