JPH06509226A - 組み替え蛋白質の製造法及び用いられる宿主細胞 - Google Patents
組み替え蛋白質の製造法及び用いられる宿主細胞Info
- Publication number
- JPH06509226A JPH06509226A JP5502002A JP50200293A JPH06509226A JP H06509226 A JPH06509226 A JP H06509226A JP 5502002 A JP5502002 A JP 5502002A JP 50200293 A JP50200293 A JP 50200293A JP H06509226 A JPH06509226 A JP H06509226A
- Authority
- JP
- Japan
- Prior art keywords
- protein
- yeast
- gene
- host cells
- plasmid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 29
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 title claims description 25
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 title claims description 25
- 108090000623 proteins and genes Proteins 0.000 claims description 68
- 210000004027 cell Anatomy 0.000 claims description 37
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 33
- 239000012634 fragment Substances 0.000 claims description 33
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- 239000013612 plasmid Substances 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 23
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 12
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 12
- 241001138401 Kluyveromyces lactis Species 0.000 claims description 8
- 230000004927 fusion Effects 0.000 claims description 8
- -1 serum albuminase Substances 0.000 claims description 7
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
- 230000003362 replicative effect Effects 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 239000003914 blood derivative Substances 0.000 claims description 5
- 239000013613 expression plasmid Substances 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 230000003248 secreting effect Effects 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 238000013518 transcription Methods 0.000 claims description 4
- 230000035897 transcription Effects 0.000 claims description 4
- 102000002572 Alpha-Globulins Human genes 0.000 claims description 3
- 108010068307 Alpha-Globulins Proteins 0.000 claims description 3
- 108700023418 Amidases Proteins 0.000 claims description 3
- 239000004382 Amylase Substances 0.000 claims description 3
- 102000013142 Amylases Human genes 0.000 claims description 3
- 108010065511 Amylases Proteins 0.000 claims description 3
- 102000006734 Beta-Globulins Human genes 0.000 claims description 3
- 108010087504 Beta-Globulins Proteins 0.000 claims description 3
- 102000007644 Colony-Stimulating Factors Human genes 0.000 claims description 3
- 108010071942 Colony-Stimulating Factors Proteins 0.000 claims description 3
- 241000701022 Cytomegalovirus Species 0.000 claims description 3
- 102000003951 Erythropoietin Human genes 0.000 claims description 3
- 108090000394 Erythropoietin Proteins 0.000 claims description 3
- 101150021185 FGF gene Proteins 0.000 claims description 3
- 108010051696 Growth Hormone Proteins 0.000 claims description 3
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 3
- 102000004877 Insulin Human genes 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- 102000015696 Interleukins Human genes 0.000 claims description 3
- 108010063738 Interleukins Proteins 0.000 claims description 3
- 102000008072 Lymphokines Human genes 0.000 claims description 3
- 108010074338 Lymphokines Proteins 0.000 claims description 3
- 101710098940 Pro-epidermal growth factor Proteins 0.000 claims description 3
- 102100038803 Somatotropin Human genes 0.000 claims description 3
- 102000005922 amidase Human genes 0.000 claims description 3
- 235000019418 amylase Nutrition 0.000 claims description 3
- 230000000890 antigenic effect Effects 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 229940105423 erythropoietin Drugs 0.000 claims description 3
- 239000000122 growth hormone Substances 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 239000003550 marker Substances 0.000 claims description 3
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 3
- 230000010076 replication Effects 0.000 claims description 3
- 230000000087 stabilizing effect Effects 0.000 claims description 3
- 239000002753 trypsin inhibitor Substances 0.000 claims description 3
- 229960005486 vaccine Drugs 0.000 claims description 3
- 210000004885 white matter Anatomy 0.000 claims description 3
- 102100035882 Catalase Human genes 0.000 claims description 2
- 108010053835 Catalase Proteins 0.000 claims description 2
- 102000004882 Lipase Human genes 0.000 claims description 2
- 108090001060 Lipase Proteins 0.000 claims description 2
- 239000004367 Lipase Substances 0.000 claims description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims description 2
- 230000002759 chromosomal effect Effects 0.000 claims description 2
- 230000002414 glycolytic effect Effects 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims description 2
- 235000019421 lipase Nutrition 0.000 claims description 2
- 108020003175 receptors Proteins 0.000 claims description 2
- 102000005962 receptors Human genes 0.000 claims description 2
- 108010054218 Factor VIII Proteins 0.000 claims 2
- 102000001690 Factor VIII Human genes 0.000 claims 2
- 229960000301 factor viii Drugs 0.000 claims 2
- 102000016359 Fibronectins Human genes 0.000 claims 1
- 108010067306 Fibronectins Proteins 0.000 claims 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims 1
- 210000005238 principal cell Anatomy 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 108010047303 von Willebrand Factor Proteins 0.000 claims 1
- 102100036537 von Willebrand factor Human genes 0.000 claims 1
- 229960001134 von willebrand factor Drugs 0.000 claims 1
- 102000009027 Albumins Human genes 0.000 description 18
- 108010088751 Albumins Proteins 0.000 description 18
- 230000014509 gene expression Effects 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 239000013598 vector Substances 0.000 description 13
- 101150050575 URA3 gene Proteins 0.000 description 11
- 239000002609 medium Substances 0.000 description 10
- 241000235649 Kluyveromyces Species 0.000 description 9
- 230000028327 secretion Effects 0.000 description 8
- 238000010276 construction Methods 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 6
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 5
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 101100029886 Caenorhabditis elegans lov-1 gene Proteins 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- 101150094690 GAL1 gene Proteins 0.000 description 4
- 102100028501 Galanin peptides Human genes 0.000 description 4
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 244000057717 Streptococcus lactis Species 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 239000007222 ypd medium Substances 0.000 description 4
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 3
- SEHFUALWMUWDKS-UHFFFAOYSA-N 5-fluoroorotic acid Chemical compound OC(=O)C=1NC(=O)NC(=O)C=1F SEHFUALWMUWDKS-UHFFFAOYSA-N 0.000 description 3
- 108090000746 Chymosin Proteins 0.000 description 3
- 101150038242 GAL10 gene Proteins 0.000 description 3
- 102100024637 Galectin-10 Human genes 0.000 description 3
- 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 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101100246753 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) pyrF gene Proteins 0.000 description 3
- 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 3
- 239000004365 Protease Substances 0.000 description 3
- 229910009523 YCl3 Inorganic materials 0.000 description 3
- 229940080701 chymosin Drugs 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- GNOLWGAJQVLBSM-UHFFFAOYSA-N n,n,5,7-tetramethyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=C(C)C=C2C(N(C)C)CCCC2=C1C GNOLWGAJQVLBSM-UHFFFAOYSA-N 0.000 description 3
- 101150047627 pgk gene Proteins 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- PCMOZDDGXKIOLL-UHFFFAOYSA-K yttrium chloride Chemical compound [Cl-].[Cl-].[Cl-].[Y+3] PCMOZDDGXKIOLL-UHFFFAOYSA-K 0.000 description 3
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 2
- 108010051457 Acid Phosphatase Proteins 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
- 102000007592 Apolipoproteins Human genes 0.000 description 2
- 108010071619 Apolipoproteins Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- 241000235346 Schizosaccharomyces Species 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 108070000030 Viral receptors Proteins 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 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 2
- 238000004458 analytical method Methods 0.000 description 2
- 101150057950 aph gene Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- 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 1
- IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 101100459439 Caenorhabditis elegans nac-2 gene Proteins 0.000 description 1
- 101100148606 Caenorhabditis elegans pst-1 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010055018 Gingival cyst Diseases 0.000 description 1
- 101000658545 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) Type I restriction enyme HindI endonuclease subunit Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 102000034452 Methionyl aminopeptidases Human genes 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 241000828418 Neomicrococcus lactis Species 0.000 description 1
- 101150002582 PSPH gene Proteins 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 241001135910 Phage M13mp18 Species 0.000 description 1
- 241000724206 Phage M13mp7 Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000311088 Schwanniomyces Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 241000121220 Tricholoma matsutake Species 0.000 description 1
- 102000018265 Virus Receptors Human genes 0.000 description 1
- 108010066342 Virus Receptors Proteins 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 101150015886 nuc-1 gene Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000003016 pheromone Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 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
- C12N15/01—Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
-
- 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
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
- C12N15/815—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts for yeasts other than Saccharomyces
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR91/08217 | 1991-07-02 | ||
| FR9108217A FR2678636A1 (fr) | 1991-07-02 | 1991-07-02 | Procede de production de proteines recombinantes et cellules hote utilisees. |
| PCT/FR1992/000610 WO1993001274A1 (fr) | 1991-07-02 | 1992-06-30 | Procede de production de proteines recombinantes et cellules hotes utilisees |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06509226A true JPH06509226A (ja) | 1994-10-20 |
Family
ID=9414582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5502002A Pending JPH06509226A (ja) | 1991-07-02 | 1992-06-30 | 組み替え蛋白質の製造法及び用いられる宿主細胞 |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP0521767A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JPH06509226A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE250126T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2278392A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2110992A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE69233206T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0592574T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2203611T3 (cg-RX-API-DMAC7.html) |
| FR (1) | FR2678636A1 (cg-RX-API-DMAC7.html) |
| IE (1) | IE922148A1 (cg-RX-API-DMAC7.html) |
| NO (1) | NO934572L (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ243403A (cg-RX-API-DMAC7.html) |
| PT (1) | PT592574E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1993001274A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105063080A (zh) * | 2015-09-07 | 2015-11-18 | 复旦大学 | 不含有信号肽的在马克斯克鲁维酵母营养缺陷型菌株中进行外源基因表达的重组载体 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3381090D1 (de) * | 1982-05-19 | 1990-02-15 | Gist Brocades Nv | Klonierungssystem fuer kluyveromyce spezies. |
| IT1203758B (it) * | 1986-03-27 | 1989-02-23 | Univ Roma | Vettori di clonazione e di espressione di geni eterologhi in lieviti e lieviti trasformati con tali vettori |
| AU628018B2 (en) * | 1987-07-28 | 1992-09-10 | Dsm Ip Assets B.V. | Kluyveromyces as a host strain |
| FR2649991B2 (fr) * | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
-
1991
- 1991-07-02 FR FR9108217A patent/FR2678636A1/fr active Granted
-
1992
- 1992-06-30 PT PT92915114T patent/PT592574E/pt unknown
- 1992-06-30 EP EP92401848A patent/EP0521767A1/fr active Pending
- 1992-06-30 EP EP92915114A patent/EP0592574B1/fr not_active Expired - Lifetime
- 1992-06-30 ES ES92915114T patent/ES2203611T3/es not_active Expired - Lifetime
- 1992-06-30 JP JP5502002A patent/JPH06509226A/ja active Pending
- 1992-06-30 CA CA002110992A patent/CA2110992A1/fr not_active Abandoned
- 1992-06-30 DE DE69233206T patent/DE69233206T2/de not_active Expired - Lifetime
- 1992-06-30 DK DK92915114T patent/DK0592574T3/da active
- 1992-06-30 AT AT92915114T patent/ATE250126T1/de active
- 1992-06-30 WO PCT/FR1992/000610 patent/WO1993001274A1/fr not_active Ceased
- 1992-06-30 AU AU22783/92A patent/AU2278392A/en not_active Abandoned
- 1992-07-01 NZ NZ243403A patent/NZ243403A/en unknown
- 1992-07-01 IE IE214892A patent/IE922148A1/en not_active Application Discontinuation
-
1993
- 1993-12-13 NO NO934572A patent/NO934572L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT592574E (pt) | 2004-02-27 |
| NO934572D0 (no) | 1993-12-13 |
| DE69233206D1 (de) | 2003-10-23 |
| FR2678636B1 (cg-RX-API-DMAC7.html) | 1994-08-19 |
| NO934572L (no) | 1993-12-13 |
| ES2203611T3 (es) | 2004-04-16 |
| NZ243403A (en) | 1994-12-22 |
| CA2110992A1 (fr) | 1993-01-21 |
| EP0592574B1 (fr) | 2003-09-17 |
| EP0521767A1 (fr) | 1993-01-07 |
| DK0592574T3 (da) | 2004-01-19 |
| EP0592574A1 (fr) | 1994-04-20 |
| ATE250126T1 (de) | 2003-10-15 |
| DE69233206T2 (de) | 2004-07-01 |
| FR2678636A1 (fr) | 1993-01-08 |
| AU2278392A (en) | 1993-02-11 |
| WO1993001274A1 (fr) | 1993-01-21 |
| IE922148A1 (en) | 1993-01-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5593858A (en) | Highly stable recombinant yeasts for the production of recombinant proteins | |
| EP0073657B1 (en) | Preparation of hepatitis b surface antigen in yeast | |
| JPH03143385A (ja) | 酵母細胞 | |
| Okabayashi et al. | Secretory expression of the human serum albumin gene in the yeast, Saccharomyces cerevisiae | |
| US5627046A (en) | Yeast promoter and its use | |
| US4803164A (en) | Preparation of hepatitis b surface antigen in yeast | |
| EP0399455B1 (en) | Stably transformed yeast host cells and their use for the production of albumin | |
| US5633146A (en) | Method for producing recombinant proteins and host cells used therein | |
| US4940661A (en) | Metallothionein transcription control sequences and use thereof | |
| IE921395A1 (en) | Yeast promoter and its use | |
| EP0362183B1 (en) | Process for the production of human lysozyme | |
| US5068185A (en) | Trains of yeast for the expression of heterologous genes | |
| USRE37447E1 (en) | Modified Kluyveromyces yeasts, their preparation and use | |
| JPH08500014A (ja) | K.ラクチス(K.lactis)トランスアルドラーゼ遺伝子のプロモーターおよびその使用 | |
| JP2855130B2 (ja) | 異種蛋白発現用融合酵母菌、該菌の製造方法および異種蛋白の製造方法 | |
| US5756313A (en) | Albumin gene-containing plasmid, transformant carrying same, production of such transformant and production of albumin | |
| JPH06509226A (ja) | 組み替え蛋白質の製造法及び用いられる宿主細胞 | |
| JPH08500007A (ja) | K.ラクチス(K.lactis)のピルビン酸デカルボキシラーゼ遺伝子のプロモーターおよびその使用 | |
| JPH08500008A (ja) | K.ラクチス(K.lactis)リボソームタンパク質RP28の遺伝子のプロモーターおよびその使用 | |
| WO2017122638A1 (ja) | 形質転換体、およびトランスフェリンの製造方法 | |
| JPS63152982A (ja) | 新規dnaおよびその用途 | |
| JP2024528145A (ja) | タンパク質合成および分泌のための方法および組成物 | |
| EP0216573A1 (en) | Yeast promoter and method of producing heterologous proteins | |
| JPH08511161A (ja) | 酵母プロモーターおよびその使用 | |
| JPS62151181A (ja) | 新規dnaおよびその用途 |