SK5593A3 - Process for preparing lovastatin - Google Patents

Process for preparing lovastatin Download PDF

Info

Publication number: SK5593A3
Authority: SK; Slovakia
Prior art keywords: lovastatin; strain; oryzae; aspergillus; fungal
Prior art date: 1992-02-10

Application number

SK55-93A

Other languages

English (en)

Slovak (sk)

Inventor

Jagroop S Dahiya

Original Assignee

Novopharm Ltd

Priority date (The priority date 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 date listed.)

1992-02-10

Filing date

1993-02-02

Publication date

1993-12-08

1992-02-27 Priority claimed from CA002062023A external-priority patent/CA2062023A1/en

1993-02-02 Application filed by Novopharm Ltd filed Critical Novopharm Ltd

1993-12-08 Publication of SK5593A3 publication Critical patent/SK5593A3/sk

Links

PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 title claims abstract description 62
229960004844 lovastatin Drugs 0.000 title claims abstract description 62
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 title claims abstract description 62
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 title claims abstract description 61
238000004519 manufacturing process Methods 0.000 title claims description 16
238000000034 method Methods 0.000 claims abstract description 24
240000006439 Aspergillus oryzae Species 0.000 claims abstract description 22
241001465318 Aspergillus terreus Species 0.000 claims abstract description 16
230000002538 fungal effect Effects 0.000 claims abstract description 11
241000228212 Aspergillus Species 0.000 claims abstract description 7
210000001938 protoplast Anatomy 0.000 claims description 17
230000009466 transformation Effects 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 9
102000004190 Enzymes Human genes 0.000 claims description 8
108090000790 Enzymes Proteins 0.000 claims description 8
239000003550 marker Substances 0.000 claims description 8
241000894007 species Species 0.000 claims description 8
235000015097 nutrients Nutrition 0.000 claims description 5
108090000623 proteins and genes Proteins 0.000 claims description 5
238000011084 recovery Methods 0.000 claims description 5
241000351920 Aspergillus nidulans Species 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
244000005700 microbiome Species 0.000 claims description 4
241000228197 Aspergillus flavus Species 0.000 claims description 3
241001225321 Aspergillus fumigatus Species 0.000 claims description 3
241000228245 Aspergillus niger Species 0.000 claims description 3
238000007273 lactonization reaction Methods 0.000 claims description 3
238000000638 solvent extraction Methods 0.000 claims description 3
150000001261 hydroxy acids Chemical class 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
238000003786 synthesis reaction Methods 0.000 claims description 2
241000228257 Aspergillus sp. Species 0.000 claims 3
230000002194 synthesizing effect Effects 0.000 claims 2
238000000855 fermentation Methods 0.000 abstract description 9
230000004151 fermentation Effects 0.000 abstract description 9
235000002247 Aspergillus oryzae Nutrition 0.000 abstract description 6
YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 21
239000002609 medium Substances 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000011534 incubation Methods 0.000 description 7
239000000203 mixture Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
238000001228 spectrum Methods 0.000 description 6
238000002474 experimental method Methods 0.000 description 5
230000008929 regeneration Effects 0.000 description 5
238000011069 regeneration method Methods 0.000 description 5
229920001817 Agar Polymers 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
239000008272 agar Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
239000002689 soil Substances 0.000 description 4
239000000243 solution Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
241000233866 Fungi Species 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
238000011081 inoculation Methods 0.000 description 3
239000013587 production medium Substances 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
230000001954 sterilising effect Effects 0.000 description 3
238000004659 sterilization and disinfection Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000008399 tap water Substances 0.000 description 3
235000020679 tap water Nutrition 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
108010073771 Soybean Proteins Proteins 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
244000309466 calf Species 0.000 description 2
210000002421 cell wall Anatomy 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000001172 regenerating effect Effects 0.000 description 2
238000011218 seed culture Methods 0.000 description 2
239000002904 solvent Substances 0.000 description 2
229940001941 soy protein Drugs 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
-1 tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl Chemical group 0.000 description 2
210000001541 thymus gland Anatomy 0.000 description 2
229960005486 vaccine Drugs 0.000 description 2
XNCSCQSQSGDGES-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]propyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C(C)CN(CC(O)=O)CC(O)=O XNCSCQSQSGDGES-UHFFFAOYSA-N 0.000 description 1
101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 1
241000219495 Betulaceae Species 0.000 description 1
244000223760 Cinnamomum zeylanicum Species 0.000 description 1
238000007400 DNA extraction Methods 0.000 description 1
240000008570 Digitaria exilis Species 0.000 description 1
235000005459 Digitaria exilis Nutrition 0.000 description 1
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
WQZGKKKJIJFFOK-ZZWDRFIYSA-N L-glucose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-ZZWDRFIYSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
241000233855 Orchidaceae Species 0.000 description 1
239000001888 Peptone Substances 0.000 description 1
235000010575 Pueraria lobata Nutrition 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
150000007960 acetonitrile Chemical class 0.000 description 1
239000002253 acid Substances 0.000 description 1
238000005273 aeration Methods 0.000 description 1
229960000723 ampicillin Drugs 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
230000002925 chemical effect Effects 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
235000017803 cinnamon Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
210000002314 coated vesicle Anatomy 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
230000018842 conidium formation Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
239000002038 ethyl acetate fraction Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000000054 fungal extract Substances 0.000 description 1
230000035784 germination Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
210000004209 hair Anatomy 0.000 description 1
125000001145 hydrido group Chemical group *[H] 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000007003 mineral medium Substances 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
XAMUDJHXFNRLCY-UHFFFAOYSA-N phenthoate Chemical compound CCOC(=O)C(SP(=S)(OC)OC)C1=CC=CC=C1 XAMUDJHXFNRLCY-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
238000007670 refining Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
229960001225 rifampicin Drugs 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000014616 translation Effects 0.000 description 1
238000011282 treatment Methods 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/42—Hydroxy-carboxylic acids
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A20/00—Water conservation; Efficient water supply; Efficient water use
- Y02A20/40—Protecting water resources
- Y02A20/402—River restoration

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Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Wood Science & Technology (AREA)
Zoology (AREA)
Bioinformatics & Cheminformatics (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
Biochemistry (AREA)
Microbiology (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
Physics & Mathematics (AREA)
Biophysics (AREA)
General Chemical & Material Sciences (AREA)
Plant Pathology (AREA)
Mycology (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

SK55-93A 1992-02-10 1993-02-02 Process for preparing lovastatin SK5593A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US83349692A	1992-02-10	1992-02-10
CA002062023A CA2062023A1 (en)	1992-02-10	1992-02-27	Novel fungal strains and use thereof in antibiotic production

Publications (1)

Publication Number	Publication Date
SK5593A3 true SK5593A3 (en)	1993-12-08

Family

ID=25674996

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK55-93A SK5593A3 (en)	1992-02-10	1993-02-02	Process for preparing lovastatin

Country Status (18)

Country	Link
EP (1)	EP0556699A1 (cs)
JP (1)	JPH0622780A (cs)
CN (1)	CN1076965A (cs)
AU (1)	AU667498B2 (cs)
BG (1)	BG61180B1 (cs)
BR (1)	BR9300467A (cs)
CZ (1)	CZ17293A3 (cs)
EE (1)	EE03048B1 (cs)
FI (1)	FI930561A7 (cs)
HR (1)	HRP930134A2 (cs)
HU (1)	HUT67061A (cs)
IL (1)	IL104481A0 (cs)
LV (1)	LV10502B (cs)
NO (1)	NO930446L (cs)
NZ (1)	NZ245713A (cs)
PL (1)	PL297691A1 (cs)
SI (1)	SI9300068A (cs)
SK (1)	SK5593A3 (cs)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5849881A (en) *	1989-05-05	1998-12-15	Baylor College Medicine	Production of recombinant lactoferrin and lactoferrin polypeptides using cDNA sequences in various organisms
IL94183A (en)	1989-05-05	2003-09-17	Baylor College Medicine	cDNA SEQUENCE CODING FOR HUMAN LACTOFERRIN PROTEIN OR PORTION THEREOF AND LACTOFERRIN PROTEIN PRODUCED FROM SAID SEQUENCE
US5766939A (en) *	1989-05-05	1998-06-16	Baylor College Of Medicine	Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms
US6100054A (en) *	1989-05-05	2000-08-08	Baylor College Of Medicine	Production for recombinant lactoferrin and lactoferrin polypeptides using DNA sequences in various organisms
US5571691A (en) *	1989-05-05	1996-11-05	Baylor College Of Medicine	Production of recombinant lactoferrin and lactoferrin polypeptides using CDNA sequences in various organisms
SI9300303A (en) *	1993-06-08	1994-12-31	Krka Tovarna Zdravil	Process for isolation of hypolipemic effective substance
US5849541A (en)	1993-11-02	1998-12-15	Merck & Co., Inc.	DNA encoding triol polyketide synthase
US6221637B1 (en)	1996-03-05	2001-04-24	Takeda Chemical Industries, Ltd.	Xanthene derivatives, their production and use
US6111081A (en) *	1996-05-31	2000-08-29	Baylor College Of Medicine	Lactoferrin variants and uses thereof
CZ299290B6 (cs) *	1997-02-20	2008-06-11	Dsm Ip Assets B.V.	Zpusob výroby beta-laktamové slouceniny, zpusob prípravy a/nebo zlepšení vláknitého mikrobiálního kmene a použití chemicky definovaného fermentacníhomédia
NZ500870A (en) *	1998-03-20	2002-03-01	Biogal Gyogyszergyar	Metabolic controlled fermentation process for preparing mevinolin (lovastatin)
US6391583B1 (en)	1998-12-18	2002-05-21	Wisconsin Alumni Research Foundation	Method of producing antihypercholesterolemic agents
EP1176208A1 (en) *	2000-07-28	2002-01-30	Société des Produits Nestlé S.A.	Koji molds and use thereof for preparing cholesterol-lowering products
WO2002064809A2 (en)	2001-02-09	2002-08-22	Unilever N.V.	Process for the preparation of one or more statins by fermentation
KR100423892B1 (ko) *	2001-12-03	2004-03-22	씨제이 주식회사	스타틴의 제조에 있어서 새로운 락톤화 방법
WO2006035295A1 (en) *	2004-09-27	2006-04-06	Ranbaxy Laboratories Limited	Process for the purification of lovastatin
CN102533893A (zh) *	2010-12-09	2012-07-04	浙江海正药业股份有限公司	一种制备莫那可林j的方法
CN104277980B (zh) *	2013-07-09	2020-04-21	丰益(上海)生物技术研发中心有限公司	分离纯化米曲霉转化子的方法
CN105602856B (zh) *	2015-12-16	2019-04-16	浙江师范大学	黑曲霉（Aspergillus niger）An-19菌株及其用于洛伐他汀的生产的用途和发酵方法
CN108118042B (zh) *	2016-11-30	2021-01-15	中国科学院青岛生物能源与过程研究所	2-甲基丁酸侧链水解酶和产莫纳可林j的曲霉菌株及其构建方法与应用
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1993
- 1993-01-20 NZ NZ245713A patent/NZ245713A/en unknown
- 1993-01-22 IL IL104481A patent/IL104481A0/xx unknown
- 1993-01-28 AU AU32121/93A patent/AU667498B2/en not_active Ceased
- 1993-02-02 SK SK55-93A patent/SK5593A3/sk unknown
- 1993-02-03 BR BR9300467A patent/BR9300467A/pt not_active Application Discontinuation
- 1993-02-08 HR HR930134A patent/HRP930134A2/hr not_active Application Discontinuation
- 1993-02-09 FI FI930561A patent/FI930561A7/fi not_active Application Discontinuation
- 1993-02-09 EP EP93102016A patent/EP0556699A1/en not_active Withdrawn
- 1993-02-09 NO NO93930446A patent/NO930446L/no unknown
- 1993-02-09 BG BG97421A patent/BG61180B1/bg unknown
- 1993-02-10 HU HU9300330A patent/HUT67061A/hu unknown
- 1993-02-10 SI SI19939300068A patent/SI9300068A/sl unknown
- 1993-02-10 CZ CZ93172A patent/CZ17293A3/cs unknown
- 1993-02-10 LV LVP-93-115A patent/LV10502B/en unknown
- 1993-02-10 CN CN93102686A patent/CN1076965A/zh active Pending
- 1993-02-10 PL PL29769193A patent/PL297691A1/xx unknown
- 1993-02-10 JP JP5061492A patent/JPH0622780A/ja active Pending
1994
- 1994-11-14 EE EE9400129A patent/EE03048B1/xx unknown

Also Published As

Publication number	Publication date
FI930561L (fi)	1993-08-11
AU3212193A (en)	1993-08-12
PL297691A1 (en)	1994-01-24
FI930561A0 (fi)	1993-02-09
NO930446L (no)	1993-08-11
HRP930134A2 (en)	1995-10-31
HU9300330D0 (en)	1993-04-28
LV10502B (en)	1995-08-20
JPH0622780A (ja)	1994-02-01
EP0556699A1 (en)	1993-08-25
AU667498B2 (en)	1996-03-28
NZ245713A (en)	1994-12-22
IL104481A0 (en)	1993-05-13
CZ17293A3 (en)	1993-12-15
EE03048B1 (et)	1997-10-15
HUT67061A (en)	1995-01-30
BR9300467A (pt)	1993-08-17
CN1076965A (zh)	1993-10-06
BG97421A (bg)	1994-03-24
NO930446D0 (no)	1993-02-09
FI930561A7 (fi)	1993-08-11
SI9300068A (en)	1993-09-30
LV10502A (lv)	1995-02-20
BG61180B1 (bg)	1997-02-28

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