CN103173390A - Chromobacterium violaceum strain and application thereof - Google Patents
Chromobacterium violaceum strain and application thereof Download PDFInfo
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Abstract
The invention discloses a new chromobacterium violaceum strain and application thereof. The new chromobacterium violaceum strain is called as Chromobacterium sp. HS-13-94, and the preservation No. is CGMCC (china general microbiological culture collection center) No.6247. The Chromobacterium sp. HS-13-94 disclosed by the invention can generate disulfide-bond depsipeptide type compound as an active substance, the compound has great inhibition effect in tumor cells such as lung cancer epithelial cell A549 and HepG (hepatoma carcinoma cell) of human body and has the characteristic of wide antitumor spectrum, and excellent business development prospect is shown.
Description
Technical field
The present invention relates to the microbial engineering field, relate in particular to a strain chromobacterium and contain application in the depsipeptide compounds of cystine linkage in preparation.
Background technology
Malignant tumour is one of serious disease that threatens human health.For a long time, oncotherapy is the key subjects of medical circle research always, and the new drug of searching treatment malignant tumour is pharmaceuticals researcher's top priority especially.In antitumor drug, the medicine with optionally anticancer growth of research and development non-cytotoxicity is the research emphasis of present antitumor drug.In recent years, a dependent metalloprotease of Zn-like ions---histone deacetylase (histone deacetylases, HDACs) becomes the focus of antitumor drug research.HDACs has participated in the adjusting of many functional protein activity in cell, as: histone, tumor-inhibiting factor p53, heat shock protein 90 (HSP90), alpha-tubulin etc.These protein and apoptosis, tumour occur and shift closely relatedly, and the expression level of HDACs is all very high in a lot of tumour cells, play an important role in the propagation of cancer cells, in shifting.Micromolecular inhibitor (HDACi) has become an available strategy of exploitation wide spectrum non-cytotoxicity antitumor drug take HDACs as shot design.
Disclosing chromobacterium (Chromobacterium sp.) in US4977138 can ferment and produce a kind of depsipeptide anti-tumor compounds romidepsin (romidepsin).In its structure, distinctive disulfide linkage is the active crucial group of performance.Due to stable hydrophobic structure, romidepsin easily sees through the cytolemma of tumour, and its disulfide linkage is reduced into the effect of sulfydryl performance histone deacetylase (HDACs) inhibitor by gsh in born of the same parents.Drugs approved by FDA romidepsin was used for the treatment of skin T-cell lymphoma (CTCL) in 2004.The present invention is from a kind of new chromobacterium bacterial strain HS-13-94 (Chromobacterium sp.HS-13-94, be deposited in China Committee for Culture Collection of Microorganisms's common micro-organisms center on June 21st, 2012, be called for short CGMCC, deposit number is CGMCC No.6247) fermented liquid in isolate a kind of depsipeptide anti-tumor compounds, Spectrum Analysis proof is basic identical with romidepsin.
Summary of the invention
One of purpose of the present invention is to provide a kind of new chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94), has the ability of producing the depsipeptide compounds that contains cystine linkage, and its deposit number is CGMCC NO.6247.
The present invention also aims to provide the application of a kind of chromobacterium HS-13-94 (Chromobacterium sp.) (CGMCC NO.6247) in being prepared as follows the depsipeptide compounds that contains cystine linkage shown in formula I,
Formula I.
The present invention also provides the method for fermentative production and separation and purification formula I compound.Fermented liquid prepares this compound by steps such as extraction, concentrated, silicagel column wash-out, crystallizations.
Separate the formula I compound obtain from chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) (CGMCC NO.6247) bacterial strain fermentation liquor, through MS,
1H-NMR reaches
13The Spectrum Analysis such as C-NMR determine that a kind of molecular weight is 540.98 depsipeptide compounds.This material is carried out anti tumor activity in vitro detect, find that it has anti-tumor activity.
The present invention also comprises the secondary metabolite that the chromobacterium bacterial strain produces, and it has very strong anti-tumor activity external, and kinds of tumor cells is had good inhibition, as the IC to Human Lung Cancer epithelial cell A549
50Be 3.8nM, to the IC of liver cancer cell HepG
50Be 5.5nM.
The biological characteristics of this bacterial strain is the colonial morphology milk yellow, and circle is smooth, has an even surface, and is moistening, easily picking; Particularly gelatine liquefication negative (-) in biochemical reactions, Starch Hydrolysis positive (+), milk is solidified as the positive (+), and iced milk turns to the positive (+).
This chromobacterium bacterial strain (called after chromobacterium HS-13-94, Chromobacterium sp.HS-13-94, CGMCC NO.6247) being preserved in China Committee for Culture Collection of Microorganisms's common micro-organisms center on June 21st, 2012 (is called for short: CGMCC), address: No. 3, Yard 1, BeiChen xi Road, Chaoyang District, Beijing City Institute of Microorganism, Academia Sinica, preserving number is CGMCC No.6247, and register on the books, prove survival.
The feature of chromobacterium HS-13-94 provided by the invention (Chromobacterium sp.HS-13-94) (CGMCC NO.6247) on morphology, Physiology and biochemistry and molecular level, produce the morphology of bacterium with known romidepsin, the feature on Physiology and biochemistry compares, can assert that chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) (CGMCC NO.6247) belongs to chromobacterium and belongs to, but with at document as US Patent No. 4977138; European patent EP 0352646; Microbiotic magazine The Journal of Antibiotics, 1994,47 (3): in 301-310, disclosed romidepsin produces the bacterium difference, especially gelatine liquefication negative (-) in chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) (CGMCC NO.6247) physiological and biochemical property, Starch Hydrolysis positive (+), milk is solidified as the positive (+), and iced milk turns to the positive (+).And general chromobacterium be characterized as gelatine liquefication positive (+), Starch Hydrolysis negative (-), milk is solidified as feminine gender (-), iced milk turns to feminine gender (-), proves that thus chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) is a new bacterial strain.
Description of drawings
Fig. 1 is the HPLC collection of illustrative plates of the embodiment of the present invention 6 antitumor formula I compounds of gained;
Fig. 2 is the ESI/MS collection of illustrative plates of the embodiment of the present invention 6 antitumor formula I compounds of gained;
Fig. 3 is the embodiment of the present invention 6 antitumor formula I compounds of gained
1The H-NMR collection of illustrative plates;
Fig. 4 is the embodiment of the present invention 6 antitumor formula I compounds of gained
13The C-NMR collection of illustrative plates.
Embodiment
Embodiment 1: bacterium source
Chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94, CGMCC No.6247) is the strain marine bacteria that separation obtains from Taizhou of Zhejiang Floor of The East China Sea mud sample.
Carry out ALTERNATE SAMPLING in the zone that the East Sea, Taizhou delimited; get at random 5 sampling points; each point is got bottom silt sample 10g; put into Erlenmeyer flask; mix rear sample thief 10g, joining in an Erlenmeyer flask that the 90ml seawater is housed (has a magnetic stirring apparatus in bottle), and vortex stirs 30min; make its abundant mixing make suspension liquid, be 10
-1Bacterium liquid.With the dilution spread flat band method, above-mentioned suspension liquid and sterilized water were diluted to 10 in 1: 9 by volume
-2, 10
-3, 10
-4, 10
-5Concentration is got different extension rate bacterium liquid 0.1ml, coats in the beef-protein medium flat board, is coated with gently in media surface with the aseptic rod that is coated with, and under room temperature, standing 30min is placed on 30 ℃ of constant incubators.After bacterium colony grows, observed and recorded colony colour, transparency, bacterium colony surface, edge configuration, check it is characterized in that no consistent.Finally choose 1000 strain primary dcreening operation bacterial classifications and be inoculated in the beef-protein medium bevel, and the checking of fermenting.Thalline one ring with transfering loop picking slant culture is inoculated into respectively (every bottle contains the 30mL fermention medium) in the 250ml Erlenmeyer flask, and shaking culture is 2 days under 30 ℃ of conditions, and the standby survey of fermented liquid is lived.
The marine microorganism that has anti-tumor activity take the lung cancer epithelial cell as target sieving.The 5 above-mentioned fermented liquids of μ l are added in 200 μ l lung cancer epithelial cell nutrient solutions (different time is got a blank) respectively, then put into 5%CO
2Cultivate 48h in incubator, detect each hole photoabsorption (OD with microplate reader
490nm), thereby the judgement fermented liquid is active to the inhibition of tumor cell line.The final 1 the highest bacterial strain of strain activity that obtains is numbered HS-13-94.The method for preserving of obtained strains comprises: adopt beef extract-peptone slant medium preservation strain in-4 ℃ of refrigerators, or adopt glycerine pipe preserving process to carry out long-term preservation in-80 ℃ of Ultralow Temperature Freezers.
Embodiment 2: feature is learned in the morphology of bacterial strain (chromobacterium HS-13-94, Chromobacterium sp.HS-13-94, CGMCC No.6247) and cultivation
With reference to " common bacteria system identification handbook, " molecular cloning experiment guide " and " related content in the book such as Chinese pharmacopoeia (2010 editions XIH) is tested.The morphology of bacterial strain and cultivation are learned the feature experiment and are adopted ISP1, ISP2, ISP3, ISP4, ISP5, Gause I, calcium malate, nutrient agar medium, YMS and 10 kinds of substratum of Cha Shi substratum, cultivate after 7～10 days, observe mycelial color and pigment situation for 28 ℃.The results are shown in Table 1.
The cultural characteristic of table 1 bacterial strain 13-94 on different culture media
Embodiment 3: the physiological and biochemical property of bacterial strain (chromobacterium HS-13-94, Chromobacterium sp.HS-13-94, CGMCC NO.6247)
The utilization test of carbon source: adopt ISP9 as basic medium, the final concentration of various carbon sources is 1.0%, and it the results are shown in Table 2.
Inorganic nitrogen-sourced utilization test: adopt ISP9 as basic medium, the concentration of saltpetre and ammonium sulfate is 1.0%, and it the results are shown in Table 2.
Degrading experiment and NaCl tolerance experiment: all adopt basic medium GYEA (pH6.0).Degradation experiment the results are shown in Table 3; The NaCl tolerance experimental results is: the NaCl tolerance is relatively poor, and 1% NaCl exists and just can not grow.
Oxydase and catalase test, pH test and humid test: all adopt nutrient agar.Its result is: bacterial strain all can be grown between 7 ℃ to 45 ℃, and optimum growth temperature is 28 ℃; PH5.5-7.5 all can grow, and optimum scope is pH6.5-7.0; Oxydase and catalase test the results are shown in Table 4.
M.R, V-P and urease test: adopt " common bacteria system identification handbook method.It the results are shown in Table 4.
Physiological and biochemical test: except temperature experiment, be 28 ℃ and cultivated 5～7 days.It the results are shown in Table 4.
The Carbon and nitrogen sources of table 2 bacterial strain HS-13-94 utilize situation
The Degrading experiment result of table 3 bacterial strain HS-13-94
The physiological and biochemical property that table 4 bacterial strain HS-13-94 is main
* annotate: 0: without growth; 1: grow very weak; 2: can grow; 3: well-grown; 4: grow best; +: the positive;-: feminine gender.
Embodiment 4:16SrDNA sequential analysis and strain identification
Collect the new fresh thalli of bacterial strain to be measured, adopt the improved Pitcher method of solution bacterium enzyme process (Letters in Applied Microbiology, 1989,8:151-156) extract total DNA profiling, adopt universal primer (27F and 1495R) to carry out 16S rRNA gene amplification, the PCR product after purifying, directly carries out sequencing after testing, and order-checking is given birth to work biotechnology company limited by Shanghai and carried out.The 16S rDNA sequence of surveying after check and correction to the GenBank database in sequence relevant kind, that belong to carry out homologous sequence BLAST relatively, with the classification position of definite this bacterial strain.
In bacterial strain HS-13-94 (CGMCC NO.6247) 16S rDNA sequence and GenBank, correlated series carries out BLAST relatively, the results are shown in Table 5 (only listing the higher bacterial strain of homology in table).
The homology of table 5 bacterial strain 13-94 and relevant bacterial strain
Bacterial strain HS-13-94 (CGMCC NO.6247) finds that by 16S rDNA zone order-checking itself and chromobacterium (Chromobacterium sp.) have very high homology, the highest reaches 99%, simultaneously bacterial strain HS-13-94 (CGMCC NO.6247) is carried out the appearance features test, find that this bacterial strain and chromobacterium (Chromobacterium sp.) classification correlation parameter is very approaching, therefore bacterial strain HS-13-94 (CGMCC NO.6247) is accredited as chromobacterium (Chromobacterium sp.) bacterial strain.
In sum, HS-13-94 (CGMCC NO.6247) belongs to chromobacterium and belongs to, produce bacterium Chromobacterium violaceum968 but be different from known romidepsin on morphological feature, therefore chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) (CGMCC NO.6247) is the brand-new bacterial classification of a strain.
Embodiment 5: fermentation preparation antineoplastic compound
(1) preparation of inclined-plane thalline and cultivation
The inclined-plane adopts beef-protein medium (g/L): extractum carnis 5, peptone 10, sodium-chlor 5, agar 20, distilled water 1000ml, pH7.0-7.2, sterilization pressure 1.05kg/cm
2, 20min is cooled to 50-60 ℃ and puts the inclined-plane, and access one ring thalline was cultivated 2 days through 30 ℃.
(2) preparation of seed liquor and cultivation
Seed culture based formulas (g/L): sucrose 20, peptone 10, yeast powder 5, NaCl3, water 1000ml, pH7.0 was through 121 ℃ of sterilizations 20 minutes.The thalline inoculum size is 10
5-10
6C.f.u./mL, 30 ℃ of culture temperature, 250rpm, shaking table shaking culture 24 hours.
(3) preparation of fermention medium and cultivation
Fermentative medium formula (g/L): sucrose 40, Zulkovsky starch 30, NH
4Cl3, K
2HPO
43, pH7.0 was through 121 ℃ of sterilizations 20 minutes.The seed liquor inoculum size is 5% (volume percent).If shake flask fermentation, at 30 ℃, 250rpm shaking table shaking culture 3 days makes the fermented liquid of antineoplastic compound.
Embodiment 6: the separation and purification of antineoplastic compound and Structural Identification
(1) fermented liquid extraction
Fermented liquid 30L adds the 30L ethyl acetate, stirs, and the standing 30min of room temperature collects the supernatant liquor organic phase and separately deposits.Aqueous phase adds the 25L ethyl acetate again, stirs, and the standing 30min of room temperature collects supernatant liquor and is incorporated in the organic phase of last time extraction.
(2) concentrated organic phase
Organic phase after merging, under 40 ℃ of water-baths ,-0.1Mpa vacuum concentration is to the 40ml left and right.
(3) mix sample
After concentrated, organic phase joins in 30g column chromatography silica gel (100 orders-200 order), mixes thoroughly in grinding alms bowl, rolls after standing approximately 4h volatilizes naturally as without granulated powders.
(4) silicagel column wash-out
Add approximately 120g column chromatography silica gel (100 orders-200 order) in glass chromatography column, then will mix sample silica gel and add in chromatography column.(v/v) carries out gradient elution with ethyl acetate/acetone, and the gradient that adopts was respectively 9: 1, and 8: 2,7: 3,6: 4,5: 5, and each gradient difference wash-out 2BV (with the solvent elution of 2 times of column volumes).(developping agent is ethyl acetate: acetone=5: 1) colour developing is followed the tracks of, and when using ethyl acetate: during acetone=8: 2 wash-outs, gained elutriant TLC colour developing has obvious principal point, begins to collect this component, is concentrated into Powderedly, and approximately 8mg weighs with TLC.
(5) crystallization
Powdered samples 2ml acetone solution, condensing crystal.Crystals weighed is 6mg, purity 96%.HPLC analyzes collection of illustrative plates as shown in Figure 1.The HPLC condition is: chromatographic column: Eclipse XDB-C18 9.4mm * 250mm, moving phase: methyl alcohol: water=7: 3.
(6) Structural Identification of antineoplastic compound
The sterling of antineoplastic compound is 540.98 through its molecular weight of MS Analysis deterrmination.By
1H-NMR reaches
13C-NMR analyzes, and determines that it is a kind of depsipeptide anti-tumor compounds, and structure is as follows:
Formula I.
Embodiment 7: the pharmacology activity research of antineoplastic compound
Adopt CCK-8 method (the .Anal Commun such as document 1:Tominage H, 36, the 47-50 pages (1999); The .The Journal of Antibiotics such as document 2:Jidong Wang, 62, the 483-487 pages (2009)) cytotoxicity of detection compound.The cell harvesting of taking the logarithm vegetative period in centrifuge tube, the centrifugal 5min of 1000r/min, counting, re-suspended cell concentration to 50000/ml, 100 μ l/ holes add 96 hole microwell plates.Negative control is the cell solution of 50000 every milliliter in 100 μ l/ holes, and blank is 100 μ l cell culture fluids (RPMI1640+10% foetal calf serum).Then be placed in 37 ℃, 5%CO
2In incubator, overnight incubation.Respectively each testing compound is diluted to 10mg/ml with DMSO, then uses the cell culture fluid doubling dilution, the testing compound sample liquid of the concentration of successively decreasing successively adds in 96 porocyte culture plates, every hole 25 μ l; Negative control and blank all add the cell culture fluid of 25 μ l.Be placed in again 37 ℃, 5%CO
2Cultivate 48h in incubator.Equal 8 the multiple holes of each sample.After adding the romidepsin reagent continuation cultivation 3.5-4h of 10 μ l in each hole, measure absorbancy (OD) under the 490nm wavelength.Be calculated as follows compound to the inhibiting rate of growth of tumour cell:
Growth of tumour cell inhibiting rate %=(1-OD experiment/OD contrast) * 100%
With the different concns of same sample, the growth of tumour cell inhibiting rate is mapped and to obtain dose response curve, therefrom obtain the half casualty-producing concentrations IC of sample
50Result shows, the secondary metabolite that chromobacterium HS-13-94 (Chromobacterium sp.HS-13-94) CGMCC NO.6247 produces has a very strong anti-tumor activity external, to the IC of Human Lung gland cancer epithelial cell A549
50Be 3.8nM, to the IC of liver cancer cell HepG
50Be 5.5nM.
Claims (2)
1. a chromobacterium (Chromobacterium sp.) HS-13-94, its deposit number is CGMCC NO.6247, has the ability of producing the depsipeptide compounds that contains cystine linkage.
2. the chromobacterium HS-13-94(CGMCC NO.6247 according to claim 1) application in being prepared as follows the depsipeptide compounds that contains cystine linkage shown in the formula I,
The formula I.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104894195A (en) * | 2014-03-07 | 2015-09-09 | 上海医药工业研究院 | Fermentation culture medium for increasing yield of FK228 |
| CN105801667A (en) * | 2016-03-22 | 2016-07-27 | 浙江海正药业股份有限公司 | Method for preparing amorphous-form Romidepsin |
| WO2016155661A1 (en) * | 2015-04-03 | 2016-10-06 | 浙江海正药业股份有限公司 | Cyclic peptide compound, and preparation and use thereof |
| CN107189974A (en) * | 2017-07-31 | 2017-09-22 | 哈尔滨工业大学 | One plant of poor nutrition low-temperature denitrification bacterium and its application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1040054A (en) * | 1988-07-26 | 1990-02-28 | 藤泽药品工业株式会社 | New compound of biologically active and preparation method thereof |
| CN101801994A (en) * | 2006-12-29 | 2010-08-11 | 格洛斯特制药公司 | Preparation Romidepsin |
-
2013
- 2013-03-16 CN CN201310087484.3A patent/CN103173390B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1040054A (en) * | 1988-07-26 | 1990-02-28 | 藤泽药品工业株式会社 | New compound of biologically active and preparation method thereof |
| CN101801994A (en) * | 2006-12-29 | 2010-08-11 | 格洛斯特制药公司 | Preparation Romidepsin |
Non-Patent Citations (2)
| Title |
|---|
| 《Folia Microbiol》 20101130 M. DUR�N ，et al Chromobacterium violaceum and Its Important Metabolites - review 535-547 1－2 第55卷, 第6期 * |
| M. DURÁN ，ET AL: "Chromobacterium violaceum and Its Important Metabolites – review", 《FOLIA MICROBIOL》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104894195A (en) * | 2014-03-07 | 2015-09-09 | 上海医药工业研究院 | Fermentation culture medium for increasing yield of FK228 |
| WO2016155661A1 (en) * | 2015-04-03 | 2016-10-06 | 浙江海正药业股份有限公司 | Cyclic peptide compound, and preparation and use thereof |
| CN107428802A (en) * | 2015-04-03 | 2017-12-01 | 浙江海正药业股份有限公司 | Cyclic peptide compound and its preparation and use |
| CN107428802B (en) * | 2015-04-03 | 2021-09-28 | 浙江海正药业股份有限公司 | Cyclic peptide compounds, their preparation and use |
| CN105801667A (en) * | 2016-03-22 | 2016-07-27 | 浙江海正药业股份有限公司 | Method for preparing amorphous-form Romidepsin |
| CN105801667B (en) * | 2016-03-22 | 2019-04-09 | 浙江海正药业股份有限公司 | A method of preparing unformed romidepsin |
| CN107189974A (en) * | 2017-07-31 | 2017-09-22 | 哈尔滨工业大学 | One plant of poor nutrition low-temperature denitrification bacterium and its application |
| CN107189974B (en) * | 2017-07-31 | 2022-09-30 | 哈尔滨工业大学 | Low-temperature denitrification bacterium for poor nutrition and application thereof |
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