CA2846893A1 - Cell-free preparation of carbapenems - Google Patents
Cell-free preparation of carbapenems Download PDFInfo
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- CA2846893A1 CA2846893A1 CA2846893A CA2846893A CA2846893A1 CA 2846893 A1 CA2846893 A1 CA 2846893A1 CA 2846893 A CA2846893 A CA 2846893A CA 2846893 A CA2846893 A CA 2846893A CA 2846893 A1 CA2846893 A1 CA 2846893A1
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- 229940041011 carbapenems Drugs 0.000 title abstract description 14
- 238000002360 preparation method Methods 0.000 title description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 177
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 7
- -1 proline compound Chemical class 0.000 claims description 164
- 102000004190 Enzymes Human genes 0.000 claims description 157
- 108090000790 Enzymes Proteins 0.000 claims description 157
- 239000001257 hydrogen Substances 0.000 claims description 151
- 229910052739 hydrogen Inorganic materials 0.000 claims description 151
- 210000004027 cell Anatomy 0.000 claims description 137
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 135
- 238000000034 method Methods 0.000 claims description 119
- 125000000623 heterocyclic group Chemical group 0.000 claims description 107
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 71
- 239000006166 lysate Substances 0.000 claims description 67
- 108010044467 Isoenzymes Proteins 0.000 claims description 63
- 241000588724 Escherichia coli Species 0.000 claims description 56
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 50
- 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 claims description 49
- 239000008103 glucose Substances 0.000 claims description 48
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 44
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 44
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 210000001322 periplasm Anatomy 0.000 claims description 39
- 229930195712 glutamate Natural products 0.000 claims description 37
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 36
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- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 claims description 35
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- 229940093530 coenzyme a Drugs 0.000 claims description 35
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 claims description 35
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- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 33
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- 101710088194 Dehydrogenase Proteins 0.000 claims description 30
- KABXUUFDPUOJMW-BYPYZUCNSA-N L-glutamic 5-semialdehyde Chemical class OC(=O)[C@@H](N)CCC=O KABXUUFDPUOJMW-BYPYZUCNSA-N 0.000 claims description 28
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 28
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 27
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 26
- 150000002306 glutamic acid derivatives Chemical class 0.000 claims description 26
- 125000003107 substituted aryl group Chemical group 0.000 claims description 25
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 21
- 230000034659 glycolysis Effects 0.000 claims description 20
- 230000002934 lysing effect Effects 0.000 claims description 20
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 claims description 19
- 239000004471 Glycine Substances 0.000 claims description 18
- 102000016397 Methyltransferase Human genes 0.000 claims description 17
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- 108010043428 Glycine hydroxymethyltransferase Proteins 0.000 claims description 16
- 108010050451 2-oxoglutarate 3-dioxygenase proline Proteins 0.000 claims description 15
- 101000761250 Pectobacterium carotovorum subsp. carotovorum (5R)-carbapenem-3-carboxylate synthase Proteins 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 claims description 14
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 claims description 14
- 108010018763 Biotin carboxylase Proteins 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 108010069632 carbapenam synthetase Proteins 0.000 claims description 14
- 108010008386 malonyl-Coa reductase Proteins 0.000 claims description 14
- 210000000805 cytoplasm Anatomy 0.000 claims description 13
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- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
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- GZCGUPFRVQAUEE-VANKVMQKSA-N aldehydo-L-glucose Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-VANKVMQKSA-N 0.000 claims description 5
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- 102000002568 Multienzyme Complexes Human genes 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims 8
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- 102000005133 Glutamate 5-kinase Human genes 0.000 claims 4
- 108010012152 beta-lactam synthetase Proteins 0.000 claims 3
- 108010011384 acyl-CoA dehydrogenase (NADP+) Proteins 0.000 claims 2
- 229940000635 beta-alanine Drugs 0.000 claims 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-aminopropionic acid Natural products NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 66
- 238000011282 treatment Methods 0.000 abstract description 8
- 210000004671 cell-free system Anatomy 0.000 abstract description 3
- 235000002639 sodium chloride Nutrition 0.000 description 131
- 125000000217 alkyl group Chemical group 0.000 description 101
- 108090000623 proteins and genes Proteins 0.000 description 77
- 125000004432 carbon atom Chemical group C* 0.000 description 60
- 125000003118 aryl group Chemical group 0.000 description 55
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- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 46
- 125000000304 alkynyl group Chemical group 0.000 description 45
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- 229910052757 nitrogen Inorganic materials 0.000 description 27
- 235000013930 proline Nutrition 0.000 description 27
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 26
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
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- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 description 21
- 102000020233 phosphotransferase Human genes 0.000 description 21
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 description 20
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- GSOSVVULSKVSLQ-JJVRHELESA-N imipenem hydrate Chemical compound O.C1C(SCCNC=N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 GSOSVVULSKVSLQ-JJVRHELESA-N 0.000 description 14
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- HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 1
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- 239000004474 valine Substances 0.000 description 1
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- 235000019154 vitamin C Nutrition 0.000 description 1
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- 235000019165 vitamin E Nutrition 0.000 description 1
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- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 239000008170 walnut oil Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
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- 210000002268 wool Anatomy 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
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Classifications
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- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
- C12P17/184—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system containing a beta-lactam ring, e.g. thienamycin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C12N15/09—Recombinant DNA-technology
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- C12N9/0026—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on CH-NH groups of donors (1.5)
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- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
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- C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
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- C12Y207/02—Phosphotransferases with a carboxy group as acceptor (2.7.2)
- C12Y207/02011—Glutamate 5-kinase (2.7.2.11)
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- C12Y603/03—Cyclo-ligases (6.3.3)
- C12Y603/03004—(Carboxyethyl)arginine beta-lactam-synthase (6.3.3.4)
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- C12Y603/04—Other carbon-nitrogen ligases (6.3.4)
- C12Y603/04016—Carbamoyl-phosphate synthase (ammonia) (6.3.4.16)
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- C12Y603/05—Carbon-nitrogen ligases with glutamine as amido-N-donor (6.3.5)
- C12Y603/05005—Carbamoyl-phosphate synthase (glutamine-hydrolysing) (6.3.5.5)
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- 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
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- Y02P20/00—Technologies relating to chemical industry
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- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Oncology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Public Health (AREA)
- Veterinary Medicine (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161533039P | 2011-09-09 | 2011-09-09 | |
| US61/533,039 | 2011-09-09 | ||
| PCT/US2012/054195 WO2013036787A2 (en) | 2011-09-09 | 2012-09-07 | Cell-free preparation of carbapenems |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2846893A1 true CA2846893A1 (en) | 2013-03-14 |
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| KR20190100386A (ko) | 2017-01-06 | 2019-08-28 | 그린라이트 바이오사이언시스, 아이엔씨. | 당의 무세포 생산 |
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2012
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- 2012-09-07 US US13/606,911 patent/US9469861B2/en not_active Expired - Fee Related
- 2012-09-07 KR KR1020147009054A patent/KR20150010932A/ko not_active Withdrawn
- 2012-09-07 CA CA2846893A patent/CA2846893A1/en not_active Abandoned
- 2012-09-07 JP JP2014529904A patent/JP2014526250A/ja active Pending
- 2012-09-07 EP EP12766509.9A patent/EP2753702B1/en not_active Not-in-force
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- 2012-09-07 WO PCT/US2012/054195 patent/WO2013036787A2/en not_active Ceased
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- 2014-02-17 IL IL231010A patent/IL231010A0/en unknown
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| IL231010A0 (en) | 2014-03-31 |
| EP2753702B1 (en) | 2021-12-15 |
| US20130065878A1 (en) | 2013-03-14 |
| JP2014526250A (ja) | 2014-10-06 |
| HK1199909A1 (en) | 2015-07-24 |
| US20170096692A1 (en) | 2017-04-06 |
| US9469861B2 (en) | 2016-10-18 |
| CN104093848A (zh) | 2014-10-08 |
| SG2014014377A (en) | 2014-05-29 |
| EP2753702A2 (en) | 2014-07-16 |
| KR20150010932A (ko) | 2015-01-29 |
| WO2013036787A3 (en) | 2013-06-13 |
| WO2013036787A2 (en) | 2013-03-14 |
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