SI2367940T1 - Mutirane penicilin G acilaze - Google Patents

Mutirane penicilin G acilaze Download PDF

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Publication number
SI2367940T1
SI2367940T1 SI200931814T SI200931814T SI2367940T1 SI 2367940 T1 SI2367940 T1 SI 2367940T1 SI 200931814 T SI200931814 T SI 200931814T SI 200931814 T SI200931814 T SI 200931814T SI 2367940 T1 SI2367940 T1 SI 2367940T1
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Slovenia
Prior art keywords
acylase
penicillin
mutated
apa
semi
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SI200931814T
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English (en)
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Der Laan Jan Metske Van
Harold Monro Moody
Richard Kerkman
Der Does Thomas Van
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Dsm Sinochem Pharmaceuticals Netherlands B.V.
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Application filed by Dsm Sinochem Pharmaceuticals Netherlands B.V. filed Critical Dsm Sinochem Pharmaceuticals Netherlands B.V.
Publication of SI2367940T1 publication Critical patent/SI2367940T1/sl

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    • CCHEMISTRY; METALLURGY
    • 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
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/78Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/80Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
    • C12N9/84Penicillin amidase (3.5.1.11)
    • CCHEMISTRY; METALLURGY
    • 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
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70Vectors or expression systems specially adapted for E. coli
    • 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
    • C12P35/00Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
    • C12P35/04Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin by acylation of the substituent in the 7 position
    • 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
    • C12P37/00Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin
    • C12P37/04Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin by acylation of the substituent in the 6 position
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y305/00Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/01Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
    • C12Y305/01011Penicillin amidase (3.5.1.11), i.e. penicillin-amidohydrolase

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

Claims (12)

  1. Mutirane penicilin G acilaze Patentni zahtevki
    1. Mutirana prokariontska penicilin G acilaza,ki ima zaporedje SEQ ID No: 1 ali ima zaporedje, ki ima od 80% do 100% enakost z zaporedjem SEQ ID No: 1, pridobljenim iz divjega tipa penicilin G acilaze, značilna po tem, da ima mutant alanin na položaju B24 in ima levcin na položaju B460, v skladu s številčenjem amino kislin Escherichia coli penicilin G acilaze, ki ima zaporedje prikazano v SEQ ID No: 1.
  2. 2. Mutirana prokariontska penicilin G acilaza po zahtevku 1, ki ima levcin na položaju A3 ali ima lizin na položaju A90 ali ima glutaminsko kislino na položaju A192 in/ali ima levcin na položaju B148.
  3. 3. Nukleinska kislina, ki kodira mutirane penicilin G acilazo po kateremkoli predhodnem zahtevku.
  4. 4. Ekspresijski vektor, ki vsebuje nukleinsko kislino po zahtevku 3.
  5. 5. Gostiteljska celica, ki vsebuje ekspresijski vektor po zahtevku 4.
  6. 6. Postopek izdelave mutirane penicilin G acilaze, po kateremkoli zahtevku od 1 do 2.
  7. 7. Postopek izdelave polsintetičnega β-laktam antibiotika, ki obsega encimsko spajanje aktivirane stranske verige z jedrom β-laktama, značilen po uporabi mutirane prokariontske penicilin G acilaze po kateremkoli zahtevku od 1 do 2.
  8. 8. Postopek po zahtevku 7, kjer je polsintetični β-laktam antibiotik izbran iz skupine, ki vsebuje polsintetične peniciline in polsintetične cefalosporine.
  9. 9. Postopek po zahtevku 8, kjer je polsintetični penicilin amoksicilin ali ampicilin.
  10. 10. Postopek po zahtevku 8, kjer je polsintetični cefalosporin cefaleksin, cefadroksil ali cefradin.
  11. 11. Postopek izdelave amoksicilina v prisotnosti acilaze, kot je opisana v kateremkoli zahtevku od 1 do 2, ki katalizira HPG v aktivirani obliki na 6-APA, kjer je molsko razmerje aktiviranega HPG na 6-APA < 3.0 in je donos amoksicilina na osnovi 6-APA (mol/mol) in merjen po reakciji encimskega spajanja >90%.
  12. 12. Postopek po zahtevku 11, kjer ima acilaza lastnost proizvodnje amoksicilina od 500 mmol na liter HPMG in 530 mmol na liter 6-APA in na koncu pretvorbe, ki poteka pri pogojih opisanih v testu A, nastane manj kot 5 mmol na liter 6-APA.
SI200931814T 2008-12-23 2009-12-22 Mutirane penicilin G acilaze SI2367940T1 (sl)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP08172831 2008-12-23
EP09796734.3A EP2367940B1 (en) 2008-12-23 2009-12-22 Mutant penicillin G acylases
PCT/EP2009/067752 WO2010072765A2 (en) 2008-12-23 2009-12-22 Mutant penicillin g acylases

Publications (1)

Publication Number Publication Date
SI2367940T1 true SI2367940T1 (sl) 2018-04-30

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SI200931814T SI2367940T1 (sl) 2008-12-23 2009-12-22 Mutirane penicilin G acilaze

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US (1) US8541199B2 (sl)
EP (1) EP2367940B1 (sl)
JP (1) JP2012513196A (sl)
KR (1) KR101735126B1 (sl)
CN (2) CN103642780B (sl)
BR (1) BRPI0922510B8 (sl)
DK (1) DK2367940T3 (sl)
HR (1) HRP20180318T1 (sl)
HU (1) HUE036302T2 (sl)
LT (1) LT2367940T (sl)
MX (1) MX2011006802A (sl)
NO (1) NO2367940T3 (sl)
SG (1) SG171964A1 (sl)
SI (1) SI2367940T1 (sl)
WO (1) WO2010072765A2 (sl)

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EP2614066B1 (en) 2010-09-07 2017-11-29 DSM Sinochem Pharmaceuticals Netherlands B.V. Process for the production of cephalosporins
US20150112057A1 (en) * 2011-06-23 2015-04-23 Dsm Sinochem Pharmaceuticals Netherlands B.V. Novel crystalline cefoperazone intermediate
PL2723882T3 (pl) * 2011-06-23 2020-01-31 Centrient Pharmaceuticals Netherlands B.V. Sposób wytwarzania 3’-tiopodstawionych cefalosporyn z zastosowaniem acylazy penicyliny
WO2012175587A2 (en) 2011-06-23 2012-12-27 Dsm Sinochem Pharmaceuticals Netherlands B.V. Novel crystalline cefoperazone intermediate
WO2013057197A1 (en) 2011-10-20 2013-04-25 Dsm Sinochem Pharmaceuticals Netherlands B.V. Process for the formylation of cefamandole
WO2013057196A1 (en) 2011-10-20 2013-04-25 Dsm Sinochem Pharmaceuticals Netherlands B.V. Process for the preparation of cefamandole nafate
RU2564578C2 (ru) * 2012-04-25 2015-10-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московский государственный университет имени М.В. Ломоносова" (МГУ) МУТАНТ ПЕНИЦИЛЛИНАЦИЛАЗЫ ИЗ E.coli С УЛУЧШЕННЫМИ СВОЙСТВАМИ
CN103074320B (zh) * 2012-05-25 2018-06-08 石药集团中奇制药技术(石家庄)有限公司 含有一个或几个点突变的青霉素g酰化酶
CN103667418B (zh) * 2013-12-18 2015-03-25 华北制药河北华民药业有限责任公司 高活性β-内酰胺抗生素合成用酶的高通量筛选方法
SG11201708356PA (en) * 2015-05-07 2017-11-29 Codexis Inc Penicillin-g acylases
CN105087533B (zh) * 2015-09-30 2018-03-27 湖南福来格生物技术有限公司 一种青霉素g酰化酶的突变体及其制备方法和应用
CN105483105B (zh) * 2016-02-23 2018-08-31 上海星维生物技术有限公司 一种青霉素g酰化酶突变体
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US10745681B2 (en) * 2017-01-05 2020-08-18 Codexis, Inc. Penicillin-G acylases
CN108660127B (zh) * 2017-03-27 2021-09-21 珠海联邦制药股份有限公司 一种人工设计的青霉素g酰化酶原及其编码序列与应用
CN107099523B (zh) * 2017-06-15 2019-09-27 清华大学 头孢拉定合成酶突变体及其编码基因
KR101985911B1 (ko) * 2017-12-28 2019-06-04 아미코젠주식회사 Achromobacter sp. CCM 4824 유래 페니실린 G 아실라제 변이체 및 이의 이용
KR102363768B1 (ko) * 2019-11-15 2022-02-16 아미코젠주식회사 세파졸린 생산성이 증가된 페니실린 g 아실라제 변이체 및 이의 이용
KR20220125219A (ko) * 2020-01-08 2022-09-14 페르멘타 바이오테크 리미티드 아크로모박터 ccm4824의 돌연변이 페니실린 g 아실라아제
CN111500564B (zh) * 2020-06-02 2022-01-18 南京工业大学 青霉素g酰化酶突变体及其在酶法合成头孢孟多中的应用
WO2022195603A1 (en) * 2021-03-18 2022-09-22 Fermenta Biotech Limited A ONE STEP PROCESS FOR THE ENZYMATIC SYNTHESIS OF SEMISYNTHETIC β-LACTAM ANTIBIOTICS
CN113567607A (zh) * 2021-07-23 2021-10-29 河北冀安检测服务有限公司 一种头孢克洛中青霉素g酰基转移酶含量的检测方法
CN113584008B (zh) * 2021-07-30 2023-04-11 湖南福来格生物技术有限公司 一种青霉素g酰化酶突变体及其应用

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Also Published As

Publication number Publication date
WO2010072765A2 (en) 2010-07-01
LT2367940T (lt) 2018-03-26
KR20110099137A (ko) 2011-09-06
JP2012513196A (ja) 2012-06-14
EP2367940A2 (en) 2011-09-28
US8541199B2 (en) 2013-09-24
SG171964A1 (en) 2011-07-28
CN103642780A (zh) 2014-03-19
BRPI0922510B8 (pt) 2021-05-25
BRPI0922510B1 (pt) 2021-01-19
DK2367940T3 (en) 2018-03-05
CN102264904B (zh) 2013-10-23
BRPI0922510A2 (pt) 2015-08-04
US20110256585A1 (en) 2011-10-20
HUE036302T2 (hu) 2018-07-30
HRP20180318T1 (hr) 2018-03-23
EP2367940B1 (en) 2017-11-22
KR101735126B1 (ko) 2017-05-12
NO2367940T3 (sl) 2018-04-21
CN103642780B (zh) 2017-06-20
WO2010072765A3 (en) 2010-08-26
MX2011006802A (es) 2011-07-20
CN102264904A (zh) 2011-11-30

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