CN107099464A - A kind of sclerotium aspergillus and its method for preparing penicillic acid - Google Patents

A kind of sclerotium aspergillus and its method for preparing penicillic acid Download PDF

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CN107099464A
CN107099464A CN201710372818.XA CN201710372818A CN107099464A CN 107099464 A CN107099464 A CN 107099464A CN 201710372818 A CN201710372818 A CN 201710372818A CN 107099464 A CN107099464 A CN 107099464A
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penicillic acid
aspergillus
sclerotium
prepares
sclerotium aspergillus
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马丽英
刘为忠
张怀斌
荣先国
刘德胜
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Binzhou Medical College
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Binzhou Medical College
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14Fungi; Culture media therefor
    • C12N1/145Fungal isolates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12RINDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00Microorganisms ; Processes using microorganisms
    • C12R2001/645Fungi ; Processes using fungi
    • C12R2001/66Aspergillus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02Oxygen as only ring hetero atoms
    • C12P17/04Oxygen as only ring hetero atoms containing a five-membered hetero ring, e.g. griseofulvin, vitamin C

Abstract

The present invention relates to a kind of sclerotium aspergillus and its method for preparing penicillic acid, belong to biological technical field.A kind of sclerotium aspergillus, Classification And Nomenclature is (Aspergillus sclerotiorum), strain number is JH42, China Committee for Culture Collection of Microorganisms's common micro-organisms center (abbreviation CGMCC) was preserved on 01 16th, 2017, its deposit number is CGMCC NO.13562,18s rRNA sequences as described in sequence table.The method that the sclerotium aspergillus prepares penicillic acid, yield is up to 1.7g/L, and obtained penicillic acid purity is up to 99%.The preparation method is simple to operate, with low cost, time saving and energy saving, is easy to large-scale production, significant to exploitation, research and application of the penicillic acid in medicine and industrial and agricultural production.

Description

A kind of sclerotium aspergillus and its method for preparing penicillic acid
Technical field
The present invention relates to a kind of sclerotium aspergillus and its method for preparing penicillic acid, belong to biological technical field.
Background technology
Penicillic acid be mainly Aspergillus (A.sclerotiorum, A.ostianus, A.terreus, A.ochraceus) and The secondary metabolite of Penicillium notatum (P.melinii, P.brasilianum, P.puberulum, P.cyclopium), with wide General bioactivity.
Penicillic acid has stronger antitumor activity to many plants of tumour cells, to human breast carcinoma high-transfer cell (MDA-MB- 435) with the IC of people's liver ascitis adenocarcinoma cell (HCT-8)50Respectively 4.43 and 8.76 μ g/ml (Chem.&Biodiv.2012,9 (10),2203-2209);To human large cell lung cancer cell (NCI-H460), human breast carcinoma (MCF-7), the neural cancer cell (SF- of people 268), the IC of cancer of pancreas (MIA Pa Ca-2) and human embryonic lung cell (WI-38)50Respectively 5.80,12.80,20.00,8.00 and 57.50μM(J.Nat.Prod.2004,67,1985-1991);To murine osteosarcoma tumor cell strain (POS1) IC50For 7.8 μM (J.Nat.Prod.2013,76,297-301);It is thin to gastric carcinoma cells (MKN45), colon cancer cell (LOVO), human lung adenocarcinoma Born of the same parents system (A549), human breast carcinoma high-transfer cell (MDA-MB-435), human liver cancer cell (HepG2) and the white blood of the acute early young grain of people The IC of sick cell (HL-60)50The μ g/mL of respectively 2.85,2.21,7.46,6.28,3.67 and 0.80 (Appl.Microbiol.Biotechnol.2013,97(17),7617-7625)。
Penicillic acid also has stronger bacteriostasis, to Aeromonas hydrophila (Aeromonas hydrophilia), eel arc The minimal inhibitory concentration (MIC) of bacterium (Vibrio anguillarum) and vibrio harveyi (Vibrio harveyi) is respectively: 1.0th, 32 and 0.5mg/mL (Phytochem.Lett.2015,12,232-236);To aurococcus The minimal inhibitory concentration of (Staphylococcus aureus) and Escherichia coli (Escherichia coli) is 128g/mL (Phytochem.2017,137,165-173)。
Penicillic acid has antimalarial activity, its IC50For 16.8 μM (Phytochem.2017,137,165-173).Mould Acid has the activity of very strong weeding (Japan Patent 08-053310,1996) and coordinate plant growth (Phytochem.2005,66,1012-1016)。
Applicant sends out during research sclerotium aspergillus (A.sclerotiorum) JH42 liquid shaker fermentation product Now the bacterium can largely produce penicillic acid, be produced on a large scale, to exploitation, research of the penicillic acid in medicine and industrial and agricultural production It is significant with application.
The content of the invention
It is an object of the invention to provide a kind of sclerotium aspergillus of high yield penicillic acid, and its method for preparing penicillic acid.
The present invention is achieved by the following technical solutions:
A kind of sclerotium aspergillus, Classification And Nomenclature is (Aspergillus sclerotiorum), and strain number is JH42, in 2017 Year is preserved in China Committee for Culture Collection of Microorganisms's common micro-organisms center (abbreviation CGMCC, address in 16 days 01 month:North The institute 3 of Jing Shi Chaoyang Districts North Star West Road 1, Institute of Microorganism, Academia Sinica, postcode 100101), its deposit number is CGMCC NO.13562,18s rRNA sequences are as described in sequence table.
Sclerotium aspergillus is to cover separate in alkaline land soil sample near your east of a river sand island, purify and obtain from Shandong Province Zhanhua County Obtain, its acquisition methods includes step in detail below:
By alkaline land soil sample and sterile old seawater according to mass ratio 1:5 mixing, are sufficiently stirred for;
(2) takes 0.5mL said mixtures to be uniformly coated in PDA culture medium, after be put in 28 DEG C of insulating boxs cultivate, treat bacterium Fall the morphological feature after growing according to bacterial strain to be selected, produce sclerotium Aspergillus strain, and be named as JH42.
The method that sclerotium aspergillus prepares penicillic acid, sclerotium aspergillus JH42 is fermented to obtain the fermentate containing penicillic acid, hair The extracted purifying of ferment thing obtains penicillic acid.
The method that sclerotium aspergillus prepares penicillic acid, is comprised the following specific steps that:
(1) cultivates 7 days in 28 DEG C of incubators by sclerotium aspergillus JH42 kinds to PDA culture medium, obtains seed;
(2) the seed that (1) step is prepared is inoculated into expand in liquid fermentation medium and cultivated by, obtains fermentate;
(3) fermentates are isolated to zymotic fluid and mycelium, and zymotic fluid is extracted through extractant, mycelium digestion agent Extraction, after be concentrated under reduced pressure into without digestion agent, then extracted with extractant;
(4) zymotic fluids extract and mycelium extract merge, and decompression and concentration operation obtains medicinal extract;
(5) by step, (4) gained medicinal extract is recrystallized, obtains mould acid crystal and mother liquor;
(6), by step (5) mother liquid obtained progress silica gel column chromatography separation, is first 1 with volume ratio:3 ethyl acetate and oil Ether mixed liquor is made eluant, eluent and eluted, then with volume ratio be 2:3 ethyl acetate and petroleum ether mixed liquor makees eluant, eluent progress Elution, and collect final eluent;
(7) by step, (6) middle gained eluent is recrystallized, obtains penicillic acid.
Prepare during penicillic acid, the compound method of the PDA culture medium is:200g peeled potatoes are boiled after dicing with seawater 20 minutes, filtered through gauze must soak juice, addition 20g glucose and 18g agar in leaching juice, and be settled to 1L with seawater, at 121 DEG C Steam sterilizing 30min under HTHP.
The compound method of the fermentation medium is:50-1000g peeled potatoes boil 20 minutes, gauze with seawater after dicing Juice must be soaked by filtering, in leaching juice addition 1-100g glucose, 1-100g maltose, 1-100g mannitol, 0.1-30g yeast extracts, 0.1-1g epsom salts, 0.1-2g potassium dihydrogen phosphates;The fermentation medium is natural ph.
Preferably, the compound method of the fermentation medium is:200g peeled potatoes boil 20 minutes, yarn with seawater after dicing Cloth, which is filtered, must soak juice, addition 20g glucose, 20g maltose, 10g mannitol, 3g yeast extracts, the water sulfuric acid of 0.3g seven in leaching juice Magnesium, 0.5g potassium dihydrogen phosphates, and 1L is settled to seawater, the steam sterilizing 30min under 121 DEG C of HTHPs.
(2) middle fermentation culture conditions are to be carried out under 20-28 DEG C, 100-170rpm rotating speeds to the step, and incubation time is 5- 15 days.
Preferably, (2) middle fermentation culture conditions are to be carried out under 28 DEG C, 170rpm rotating speeds to the step, and incubation time is 9 My god.
The extractant is at least one in chloroform, dichloromethane, benzene,toluene,xylene, ethyl acetate or n-butanol Kind;Digestion agent is at least one of acetone, methanol or ethanol;Recrystallization solvent be acetone, chloroform, dichloromethane, ethyl acetate, At least one of methanol or ethanol.
Penicillic acid prepared by sclerotium aspergillus, it is colourless bulk crystals, and molecular formula is C8H10O4, chemical formula is:
The method that the sclerotium aspergillus prepares penicillic acid, yield is up to 1.7g/L, and obtained penicillic acid purity is up to 99%. The preparation method is simple to operate, with low cost, time saving and energy saving, is easy to large-scale production, and penicillic acid is given birth in medicine and industrial or agricultural Exploitation, research and application in production is significant.
Sclerotium aspergillus was preserved in China Committee for Culture Collection of Microorganisms's common micro-organisms on 01 16th, 2017 Center (abbreviation CGMCC), deposit number is CGMCC NO.13562.
Embodiment
Embodiment of the invention given below, for the present invention is further described.
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material, reagent used etc., unless otherwise specified, are commercially obtained in following embodiments.
The acquisition of sclerotium aspergillus JH42 bacterial strains
The sclerotium aspergillus JH42 of the present invention is to cover alkaline land soil sample near your east of a river sand island from Shandong Province Zhanhua County Middle separation, purifying are obtained.
Its isolation and purification method is:20g pedotheques are diluted with the sterile old seawater of 100ml, after being sufficiently mixed, taken 0.5mL mixed liquors are uniformly coated in PDA culture medium, after be put in 28 DEG C of insulating boxs cultivate, according to bacterial strain after bacterium colony is grown Morphological feature is selected, and produces sclerotium Aspergillus strain, and be named as JH42.
The compound method of the PDA culture medium is:200g peeled potatoes are boiled 20 minutes after dicing with seawater, and filtered through gauze is obtained Juice is soaked, addition 20g glucose, 18g agar and 0.2g streptomysins in leaching juice, and 1L is settled to seawater, in 121 DEG C of high temperature height Depress steam sterilizing 30min.
The identification of sclerotium aspergillus JH42 bacterial strains
By in the above-mentioned sclerotium aspergillus JH42 inoculations picked out to PDA culture medium, dark culturing 7d under the conditions of 28 DEG C.
Colony characteristicses are as follows:Colony diameter 43mm, quality is cotton-shaped;Conidium structure is rare, is concentrated mainly in bacterium colony Centre, it is faint yellow;Bacterium colony reverse side is faint yellow.
The DNA of sclerotium aspergillus JH42 bacterial strains, and the universal primer amplification in the ITS areas using fungi are extracted according to conventional methods Its ITS area, the base sequence in Jiang Qi ITS areas submits GeneBank, and its GenBank gene accession number is:HQ717801, by Blast retrievals are carried out in GenBank, it is sclerotium aspergillus JH42 to determine the bacterial strain.Its 18s rRNA sequence is as described in sequence table.
The fermenting and producing and separation and purification of penicillic acid
(1) cultivates 7 days in 28 DEG C of incubators by sclerotium aspergillus JH42 kinds to PDA culture medium, obtains seed;
(2) the seed that (1) step is prepared is inoculated into shaker fermentation culture in liquid fermentation medium by, obtains fermentate;
(3) fermentates are isolated to zymotic fluid and mycelium, and zymotic fluid is extracted through extractant, mycelium digestion agent Extraction, after be concentrated under reduced pressure into without digestion agent, then extracted with extractant;
(4) zymotic fluids extract and mycelium extract merge, and decompression and concentration operation obtains medicinal extract;
(5) by step, (4) gained medicinal extract is recrystallized, obtains mould acid crystal and mother liquor;
(6), by step (5) mother liquid obtained progress silica gel column chromatography separation, is first 1 with volume ratio:3 ethyl acetate and oil Ether mixed liquor is made eluant, eluent and eluted, then with volume ratio be 2:3 ethyl acetate and petroleum ether mixed liquor makees eluant, eluent progress Elution;
(7) by step, (6) middle gained eluent is recrystallized, obtains penicillic acid.
Produce the fermented and cultured of bacterium:By the conventional method of culture microorganism, take sclerotium aspergillus JH42 appropriate, be inoculated into PDA On plating medium, cultivated 7 days in 28 DEG C of incubators, obtain seed.
The compound method of the PDA culture medium is:200g peeled potatoes are boiled 20 minutes after dicing with seawater, and filtered through gauze is obtained Juice is soaked, addition 20g glucose and 18g agar in leaching juice, and 1L is settled to Chen Haishui, the steam under 121 DEG C of HTHPs Sterilize 30min.
The seed of preparation is inoculated into the 500mL Erlenmeyer flasks equipped with 180mL nutrient solutions, 28 DEG C of cultivation temperature, rotating speed is 170rpm, shaking table culture 9 days, obtains fermentate 34.5L.Wherein, nutrient solution composition is:200g peeled potatoes leaching juice, 20g grapes Sugar, 20g maltose, 10g mannitol, 3g yeast extracts, 0.3g epsom salts, 0.5g potassium dihydrogen phosphates, are settled to Chen Haishui 1L, the pH value of culture medium is natural.
With cotton by mycelium and separation of fermentative broth, mycelium is extracted three times with methanol, is concentrated under reduced pressure into without methanol, Gained water layer is extracted three times with isometric ethyl acetate;Zymotic fluid is extracted with ethyl acetate three times, combined ethyl acetate extract, Medicinal extract 73g is obtained after being concentrated under reduced pressure.
Medicinal extract obtains mould acid crystal 18g through acetone recrystallization, and the solution removed after the mould acid crystal of part is mother liquor. Mother liquor, through silica gel (200-300 mesh) column chromatography for separation, is first 1 with volume ratio:3 ethyl acetate and petroleum ether mixed liquor is eluted Agent is eluted, then with volume ratio be 2:3 ethyl acetate and petroleum ether mixed liquor is made eluant, eluent and eluted, collected volume ratio For 2:Containing a large amount of blue or green in the solution that 3 ethyl acetate and petroleum ether mixed liquor is eluted as mobile phase, the eluent of collection Mould acid, through acetone recrystallization, obtains penicillic acid 41g.
Above-mentioned gained penicillic acid checking is analyzed as follows:
Penicillic acid is colourless bulk crystals, mp 81-82 DEG C;UV(MeOH)λmax(logε):224(4.02);IR(ATR) νmax 3255,1739,1727,1634,1446,1345,1275,1220,1183,1166,1059,1043,1012,997,953, 900,802,781,747,692cm-1;HRESIMS m/z 169.0496[M-H]-(calcd for C8H9O4,169.0501), Molecular formula C8H10O4
1H and13C NMR datas see the table below.
In summary, sclerotium aspergillus JH42 of the present invention can largely produce penicillic acid.Used medium raw material is easy to get, and cost is low Honest and clean, fermentation period is short.
The yield that sclerotium aspergillus JH42 of the present invention prepares penicillic acid is high, and fermentation broth extract is (i.e.:Medicinal extract) up to 2.1g/L Zymotic fluid, is separated through simple silica gel column chromatography, then is carried out recrystallization operation and can be obtained purity up to 99% penicillic acid, separation The penicillic acid obtained after purification is equivalent to 1.7g/L, and yield is up to 81%.
The method that sclerotium aspergillus JH42 of the present invention prepares penicillic acid is beneficial to industrialized production, to penicillic acid in medicine and workers and peasants Developmental research in industry production is significant.
All documents referred in the present invention are all incorporated as reference in this application, independent just as each document It is incorporated as reference.Presently preferred embodiments of the present invention is the foregoing is only, is not intended to limit the invention, all essences in the present invention God is with principle, and any modification, equivalent substitution and improvements made etc. should be included in the scope of the protection.
SEQUENCE LISTING
<110>Binzhou Medical College
<120>A kind of sclerotium aspergillus and its method for preparing penicillic acid
<160> 1
<210> 1
<211> 956
<212> RNA
<213>Sclerotium aspergillus (Aspergillus sclerotiorum)
<400> 1
ggcaacattg agtgaggtac tcggggccaa cctcccaccc gtgtataccg taccttgttg 60
cttcggcggg cccgccgcgc aagcggccgc cgggggggcg tcaaaccccc ctccctaggc 120
gagcgcccgc cggagacacc aacgtgaaca ctgtctgaag ttttgttgtc tgagttcgat 180
tgtatcgcaa tcagttaaaa ctttcaacaa tggatctctt ggttccggca tcgatgaaga 240
acgcagcgaa atgcgataat taatgtgaat tgcagaattc agtgaatcat cgagtctttg 300
aacgcacatt gcaccccctg gtattccggg gggtatgcct gtccgagcgt cattgctgcc 360
ctcaagcacg gcttgtgtgt tgggtcgtcg tccccccggg gacgggcccg aaaggcagcg 420
gcggcaccgc gtccggtcct cgagcgtatg gggctttgtc acccgctctt gtaggcccgg 480
ccggcgctgg ccgacgctga aaagcaacca actatttctc caggttgacc tcggatcagg 540
tagggatacc cgctgaactt aagcatatca ataagcggag gaagatcatt actgagtgag 600
ggtccctcgg ggccaacctc caccggggta taccgtacct tgttgcttcg gcgggccgcg 660
gcaagcggcc ccgggggggc gtcaacccct cctaggcgag cgccgccgga gacaccaacg 720
tgaacactgt ctgaagtttt gttgtctgag tttcgattgt atcccaatca gttaaaaact 780
ttcaacaatg gatctcttgg ttcggcatca tgaagaacgc acgaaatgcg ataattaatg 840
tgaattgcag aaattcatga aatcatcagt cttttgtacg cacatttgcc ccctggtatt 900
tcggggggga tggcctgctc gaaacgatct tgctgcccct caacacgttg tggtgg 956

Claims (10)

1. a kind of sclerotium aspergillus, it is characterised in that:Classification And Nomenclature is sclerotium aspergillus (Aspergillus sclerotiorum) JH42, deposit number is CGMCC NO.13562,18s rRNA sequences as described in sequence table.
2. the method that sclerotium aspergillus prepares penicillic acid according to claim 1, it is characterised in that:Sclerotium aspergillus JH42 is fermented The fermentate containing penicillic acid is obtained, the extracted purifying of fermentate obtains penicillic acid.
3. the method that sclerotium aspergillus as claimed in claim 2 prepares penicillic acid, it is characterised in that:Comprise the following specific steps that:
(1) cultivates 7 days in 28 DEG C of incubators by sclerotium aspergillus JH42 kinds to PDA culture medium, obtains seed;
(2) the seed that (1) step is prepared is inoculated into shaker fermentation culture in liquid fermentation medium by, obtains fermentate;
(3) fermentates are isolated to zymotic fluid and mycelium, and zymotic fluid is extracted through extractant, and mycelium is soaked with digestion agent Carry, after be concentrated under reduced pressure into without digestion agent, then extracted with extractant;
(4) zymotic fluids extract and mycelium extract merge, and decompression and concentration operation obtains medicinal extract;
(5) by step, (4) gained medicinal extract is recrystallized, obtains mould acid crystal and mother liquor;
(6), by step (5) mother liquid obtained progress silica gel column chromatography separation, is first 1 with volume ratio:3 ethyl acetate and petroleum ether is mixed Close liquid to make eluant, eluent and eluted, then with volume ratio be 2:3 ethyl acetate and petroleum ether mixed liquor is made eluant, eluent and eluted, And collect final eluent;
(7) by step, (6) middle gained eluent is recrystallized, obtains penicillic acid.
4. the method that sclerotium aspergillus as claimed in claim 3 prepares penicillic acid, it is characterised in that:The preparation of the PDA culture medium Method is:200g peeled potatoes are boiled 20 minutes after dicing with seawater, and filtered through gauze must soak juice, and 20g glucose is added in leaching juice With 18g agar, and 1L is settled to seawater, the steam sterilizing 30min under 121 DEG C of HTHPs.
5. the method that sclerotium aspergillus as claimed in claim 3 prepares penicillic acid, it is characterised in that:The preparation of the fermentation medium Method is:50-1000g peeled potatoes are boiled 20 minutes after dicing with seawater, and filtered through gauze must soak juice, and 1-100g is added in leaching juice Glucose, 1-100g maltose, 1-100g mannitol, 0.1-30g yeast extracts, 0.1-1g epsom salts, 0.1-2g di(2-ethylhexyl)phosphates Hydrogen potassium;The fermentation medium is natural ph.
6. the method that sclerotium aspergillus as claimed in claim 5 prepares penicillic acid, it is characterised in that:The preparation of the fermentation medium Method is:200g peeled potatoes are boiled 20 minutes after dicing with seawater, and filtered through gauze must soak juice, in leaching juice addition 20g glucose, 20g maltose, 10g mannitol, 3g yeast extracts, 0.3g epsom salts, 0.5g potassium dihydrogen phosphates, and 1L is settled to seawater, The steam sterilizing 30min under 121 DEG C of HTHPs.
7. the method that sclerotium aspergillus as claimed in claim 3 prepares penicillic acid, it is characterised in that:The step (2) middle fermented and cultured Condition is to be carried out under 20-28 DEG C, 100-170rpm rotating speeds, and incubation time is 5-15 days.
8. the method that sclerotium aspergillus as claimed in claim 7 prepares penicillic acid, it is characterised in that:The step (2) middle fermented and cultured Condition is to be carried out under 28 DEG C, 170rpm rotating speeds, and incubation time is 9 days.
9. the method that sclerotium aspergillus as claimed in claim 4 prepares penicillic acid, it is characterised in that:The extractant is chloroform, two At least one of chloromethanes, benzene,toluene,xylene, ethyl acetate or n-butanol;Digestion agent is in acetone, methanol or ethanol It is at least one;Recrystallization solvent is at least one of acetone, chloroform, dichloromethane, ethyl acetate, methanol or ethanol.
10. penicillic acid prepared by sclerotium aspergillus described in claim 1, it is characterised in that:Penicillic acid is colourless bulk crystals, molecule Formula is C8H10O4, chemical formula is:
CN201710372818.XA 2017-05-24 2017-05-24 A kind of sclerotium aspergillus and its method for preparing penicillic acid Pending CN107099464A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107794229A (en) * 2017-11-24 2018-03-13 浙江师范大学 The bacterial strains of sclerotium aspergillus As 75 of antagonism rice leaf spot bacteria and its fermentation culture and application
CN109456899A (en) * 2018-10-30 2019-03-12 云南大学 A kind of method of Penicillium notatum and its fermenting and producing penicillic acid
CN111117893A (en) * 2018-10-31 2020-05-08 中国科学院青岛生物能源与过程研究所 Aspergillus terreus strain for producing 4-O-demethylbarbituric acid and application thereof

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107794229A (en) * 2017-11-24 2018-03-13 浙江师范大学 The bacterial strains of sclerotium aspergillus As 75 of antagonism rice leaf spot bacteria and its fermentation culture and application
CN107794229B (en) * 2017-11-24 2020-12-04 浙江师范大学 Aspergillus sclerotiorum As-75 strain for antagonizing rice bacterial blight and fermentation culture solution and application thereof
CN109456899A (en) * 2018-10-30 2019-03-12 云南大学 A kind of method of Penicillium notatum and its fermenting and producing penicillic acid
CN109456899B (en) * 2018-10-30 2021-10-22 云南大学 Penicillium and method for producing penicillic acid by fermenting penicillium
CN111117893A (en) * 2018-10-31 2020-05-08 中国科学院青岛生物能源与过程研究所 Aspergillus terreus strain for producing 4-O-demethylbarbituric acid and application thereof
CN111117893B (en) * 2018-10-31 2022-03-11 中国科学院青岛生物能源与过程研究所 Aspergillus terreus strain for producing 4-O-demethylbarbituric acid and application thereof

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Application publication date: 20170829