CS233318B1 - Method of 3-hydroxybutyratedehydrogenase preparation - Google Patents

Method of 3-hydroxybutyratedehydrogenase preparation Download PDF

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Publication number
CS233318B1
CS233318B1 CS8981A CS8981A CS233318B1 CS 233318 B1 CS233318 B1 CS 233318B1 CS 8981 A CS8981 A CS 8981A CS 8981 A CS8981 A CS 8981A CS 233318 B1 CS233318 B1 CS 233318B1
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Czechoslovakia
Prior art keywords
hydroxybutyrate
acetoacetate
ferment
cultivation
cultured
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CS8981A
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Czech (cs)
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Wulfdieter Schoepp
Hans-Peter Kleber
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Wulfdieter Schoepp
Kleber Hans Peter
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Publication of CS233318B1 publication Critical patent/CS233318B1/en

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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
    • C12N9/0004Oxidoreductases (1.)
    • C12N9/0006Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Compounds Of Unknown Constitution (AREA)

Description

TJI.E

o <CD m >'c r-mN< C· 30-· >o <CD m> 'c r-mN <C · 30- ·>

CJ coCJ what

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HASBAHIÍE H30BPETEHHHHASBAHIÍE H30BPETEHHH

Cnocod nojiyneHHH 3-ra.npoKCHdyTHpaTnerHnporeHa3HCnocod nojiyneHHH 3-ra.npoKCHdyTHpaTnerHnporeHa3H

OdjiaCTL· ΠρΚλΙΘΗΘΗΗΗ H30dpeTeHHH H3oópeTeHne KacaeTcn cnocoda noJiynsHHH 3-rH.npoKCHdyTHpaT-.Ιξ6ΓΙ·:ΐίρ0ΓΘΗ33Η, KOTOpHH H3X0HHT ΠρΗΜΘΗΘΗΗΘ B KJHÍHHK0—XHMH—ηθοκοη .mrarHocTHKe .ujih κοληηθοτβθηηογο onpe.nejieHHH κθτοη-HHX ΤΘΛ.OdjiaCTL · ΠρΚλΙΘΗΘΗΗΗ H30dpeTeHHH H3oópeTeHne KacaeTcn cnocoda noJiynsHHH 3-rH.npoKCHdyTHpaT .Ιξ6ΓΙ ·: ΐίρ0ΓΘΗ33Η, KOTOpHH H3X0HHT ΠρΗΜΘΗΘΗΗΘ KJHÍHHK0-B-XHMH ηθοκοη .mrarHocTHKe .ujih κοληηθοτβθηηογο onpe.nejieHHH κθτοη HHX-ΤΘΛ.

XapaKTepHCTiíKa η3βθοτηηχ τθχηηηθοκηχ pemeHHHXapaKTepHCTiiKa η3βθοτηηχ τθχηηηθοκηχ pemeHHH

Cnocod nonynemiH 3-rHnpoKCHdyTHpaT.nerHnporeHa3n yne H3-BecTOH. JBlh stoh ne jih BnpaníHBaioT daKTepnantHEH ιιιτθμμRhodopseudomonas spheroides Ha 3-rH.npOKCHdyTHpaTe, K8Khctohhhk yrjiepo.ua, 3θτθμ οτββτεηιοτ daKTepKH nocpencTBOM neHT-pH$yrHpoBaHHH, odpadaTHBaioT κχ h nonsepraioT cBodonHHH otKJieTOK deJEKOBHH 3KCTpaKT, ΗΜΘΚΙΙξΗΗ HanaJIBHyiO 8KTHBH0CTL no- - 2 - ρπηκθ 0,1 mojib/mhh/μγ denna, B03.neiicTBHio npoTaMHHcyjiB$a-Ta ujih ocax:.neHHH h nocne.nyioinero y.naneHHH HyKJieííHOBHX kkc-JIOT. IlOCJie φρδΚΠΚΟΗΧρΟΒΘΗΙΜ nOCpe.UCTBOM aMMOHHllcyJIL^iaTHOrOooaKneHEH, cooTBSTCTByiomaH $paKiw οτ.ηθηΗθτοΗ, προμηβθθτοη,pacTBopaeTcn b tíygpepe κ OHHmaeTcn Hnu se odoramaeTCH mho-roKpaTHO xpoMaTorparaHHecKlí no θκτηβηοοτη nopnnKa 17 mojib/μηη/μγ denna (toepaTypa, HanpHMep, H.U.Bergmeyer et al.,Biochem. J. (1967),102, 423). npsncTaBJíeHHHH cnocod odna.naeT τθμ Ηθ.ηοστθτκοΜ, ητο κοηθη-hhh npo.nyKT oneHB nopor, ocodeHHO ecnn neno xacaeTCH cnnB-ho odorameHHOH 3-rH.npoKCHtíyTHpaT.nerHnporeHa3H. IIpHHHHa sto-po He tojibko b Tpy.noeMKOCTH onepaiiHH ohhctkh, ho h b bhco-KOÍi CTOHMOCTH CydCTpSTa w KyJILTilBIípOBaHEH. JtaJIBHeilIIIHHΗθ,ηοοτετοκ coctoht b tom, ητο βκτηβηοοτβ nonynaeMoro φθρ-μθητθ He npeBKiiiaeT 3Η3Ηθηηη b 17 - 20 mojil/mhh/μγ dejma.HpHHHHa b tom, hto πρημθηηθμηη ιιιτθμμ Rhodopseudomongsspheroides He B COCTOHHHH np0H3B0.HHTB φθρΜβΗΤ C dOJiee BH-C0K0Í1 HanaJIBHOK aKTHBHOCTBIO, ΗΘΜ BHHieonHCaHHOH.Cnocod nonynH3-rHnpoKCHdyTHpaT.nerHnporeHa3n yne H3-BecTOH. JBlh not stack south BnpaníHBaioT daKTepnantHEH ιιιτθμμRhodopseudomonas spheroides 3-Ha rH.npOKCHdyTHpaTe, K8Khctohhhk yrjiepo.ua, 3θτθμ οτββτεηιοτ daKTepKH nocpencTBOM nails pH-$ yrHpoBaHHH, odpadaTHBaioT κχ h nonsepraioT cBodonHHH otKJieTOK deJEKOBHH 3KCTpaKT, ΗΜΘΚΙΙξΗΗ HanaJIBHyiO 8KTHBH0CTL O- - 2 - ρπηκθ 0 1 mojib / mhh / μg denna, B03.neiicTBHio npoTaMHHcyjiB $ a-Ta ujih ocax: .HHH h nocne.nyioinero y.naneHHH HyKJieííHOBHX kkc-JIOT. IlOCJie φρδΚΠΚΟΗΧρΟΒΘΗΙΜ nOCpe.UCTBOM aMMOHHllcyJIL iaTHOrOooaKneHEH ^, $ cooTBSTCTByiomaH paKiw οτ.ηθηΗθτοΗ, προμηβθθτοη, pacTBopaeTcn b tíygpepe κ OHHmaeTcn HNU is odoramaeTCH mho-roKpaTHO xpoMaTorparaHHecKlí no θκτηβηοοτη nopnnKa 17 Mojib / μηη / μγ daily (toepaTypa, HanpHMep, HUBergmeyer et al. , Biochem., J. (1967), 102, 423). npsncTaBJíeHHHH cnocod odna.naeT θ... ο ο Μ Μ H H H H H H H H H H H H H H H H H H H H H H aca aca aca aca aca aca aca aca aca aca aca aca OH OH. IIpHHHHa sto-po He tojibko b Tpy.noeMKOCTH onepaiiHH ohhctkh, ho h b bhco-KOIi CTOHMOCTH CydCTpSTa w KyJILTilBIiPOBaHEH. JtaJIBHeilIIIHHΗθ, ηοοτετοκ coctoht b that ητο βκτηβηοοτβ nonynaeMoro φθρ μθητθ Ile-npeBKiiiaeT 3Η3Ηθηηη b 17-20 mojil / MHH / b dejma.HpHHHHa μγ that HTO πρημθηηθμηη ιιιτθμμ Rhodopseudomongsspheroides He B COCTOHHHH np0H3B0.HHTB φθρΜβΗΤ C dOJiee BH-C0K0Í1 HanaJIBHOK aKTHBHOCTBIO, HBHHieonHClaHHOH.

UenB H3odpeTeHiiHUenB H3odpeTeHiiH

UejiB. ' H3odpeTeHKH coctoht b tom, HTodn naTB cnocod nonyne-hiih cpepMeHTa, κοτορκη TpedyeT 3HannTenBH0 μθηβιπηχ 3aTpaT,HeM no chx nop H3BecTHHe h no3BOJMeT CBepx Toro nonynaTBφβρΜθκτ co 3HaHHTenBH0 donee bhcokoh οπθΐίΗφΗΗθοκοΗ θκτηβ-HOCTBK).UejiB. 'B H3odpeTeHKH coctoht that HTodn NATB cnocod nonyn-Hiih cpepMeHTa, κοτορκη TpedyeT 3HannTenBH0 μθηβιπηχ 3aTpaT, heme but CHX nop H3BecTHHe h no3BOJMeT CBepx Toro nonynaTBφβρΜθκτ what 3HaHHTenBH0 donee bhcokoh οπθΐίΗφΗΗθοκοΗ θκτηβ-HOCTBK).

H3JI0SeHHe CyiItHOCTH H30dpeTeHHH B ocHO3y H3odpeTeHHH nononeHa 3a.nana Η3μθηητβ cymecTBeHHBieοτοροΗΗ y^e ηθβθοτηηχ cnooodoB BH.neJieHHn h, HcnonB3OBaB npyrae iuTaMMti, a Taiose .npyrne cydcTpaTH nnn KynBTHBHpoBaHHHb coneTaHHH o hoboh TexHonornen, nonymiTB ^enaeMHH ΦθρμθητnpOCTEM CnOCOdOM H C BHCOKOH ΟΠΘΗΗφΗΗΘΟΚΟΖ aKTHBHOCTBIO. - 3 -H3JI0SeHHe CyiItHOCTH H30dpeTeHHH B ocHO3y H3odpeTeHHH nononeHa 3a.nana Η3μθηητβ cymecTBeHHBieοτοροΗΗ y ^ e ηθβθοτηηχ cnooodoB BH.neJieHHn h HcnonB3OBaB npyrae iuTaMMti and Taiose .npyrne cydcTpaTH nnn KynBTHBHpoBaHHHb coneTaHHH of hoboh TexHonornen, nonymiTB enaeMHH ΦθρμθητnpOCTEM CnOCOdOM ^ H C BHCOKOH ΟΠΘΗΗφΗΗΘΟΚΟΖ aKTHBHOCTBIO. - 3 -

CorjiacHO n3oópeTemro pememie 3a,Hanu dnjio nocTurHyTo nyTeMΒΗΑθΛΘΗΚΗ (pepweHTa 3-rn.npoKCíidyTKpaTnernnporeHa3H H3 uiTaM-Ma Pseudomonas putida. llhraMM coxpaHHJin npenjviynecTBeHHo HadyjiLOHe c 2 % arapoM npn 4° C b τθμηοτθ. KyjiLTHBHpoBaHnePseudomonas putida ocyinecTBJíHeTcn b cydMepcHOHHon xy jíl Ty-pe Ha SH.HKOH MHHHMaJILHOH ΟρθΠθ nOCJie ΠβρβΟβΒΘΗΗΗ H3 ΠθρΒΗΗ-Hofí KyjiLTypti npH TewnepaTypax ot 20 .no 40° C (npeHMynecTBenho npn 30° C). BtipanHíBaHne corjiacHO Μ3θόρβτθΗΗΐο npoBO.nHJiocLHa τβχ HGTOHHHKax yrjiepo.na, npn pacna.ne κοτορκχ odpa3yKTcn'aueToaueTaT h m.npoKcnóyTHpaT. Tamní ηοτοηηιικθμη yrjiepo.naHBJIHIOTCH, HanpHMep, D,L -JIH3HH, D,L-JieHUHH, D,L-KapHHTHHH T.,n. H ΚρΟΜθ ΤΟΓΟ, Hepa3B6TBJieHHHe yrJieBO.nopO.HBI C HJIIIHOHnenH Cg no Cjq SHpHLie khcjioth ot C4 .no Cjg. B KanecTBeHCTOHHHKOB a30Ta npHMeHHJIHCL NH^Cl, H Τ.Π. B ΤΘΧ cjiyHanx, b κοτορπχ hctohhhk yrjiepona ne μοιςθτ óhtl o.nnoBpe-ΜΘΗΗΟ HCnOJILSOBaH H K3K HCTOHHHK a30Ta. IlOCJie BHpaiIIHBaHHH Bτθηθηηθ βρθμθηη ot 5 no 40 nacoB - b 3θβηοημοοτη οτ φΗ3Η0-jiornnecKoro cogtohhhh h KOJiinecTBa βηοθβθθμογο MaTepnaJia -. óaKTepHH coónpaJincL, HanpHMep, nyTeM neHTpii$yrapoBaHHH npo-MHBaJIHCL φΟΟψθΤΗΗΜ Óy^epOM Η B 3aKJH0HeHHe npeBpanaJIHCL BdecKJieTOHHHH rpydtni SKCTpaKT,· HanpHMep, nyTeM odpadoTKHyjrLTpa3ByxoM npn TewnepaTypax dJiH3KHX κ τοηκθ 3aMep3aHHH cnocJie.nyioiniíM neHTpHžyrHpoBaHHe m. Ηθχο.κηιιιηηοη b rpydoM skct-paKTe φβρΜθΗτ npoHBjmeT b 3aBHciLM0CTH ot ηοτοηηηκθ yrjieponanpHBe.neHHiie b Tadjinue I οπθιιηΦηηθοκηθ θκτηβηοοτη. C nOMOUfLK) mpaKHHOHHOrO OCazneHHH HJIH se 3KCTpawm cojlhmh,HanpHMep c cyjn^aTOM θμμοηηή, ocyinecTBJíneTCH 10 - 15 KpaT—Hoe odoraneHne φθρΜθΗΤθ. Hjih stopo n,ejiecoodpa3HHM HBJíHeTcnpa3Be.neHHe dejnwBoro SKCTpaKTa c nocJienywiM ocasneHiieM no-naBJíHKinero KOJinnecTBa dejina 70 % cyjn^aTOM θμμοηηη. nojman θκτηβηοοτβ ocraeTcn npn stom b οθ.κημθητθ. Azih HaJiB-Hefiiiiero odoraneHKa 3-rHnpoKCHdyTHpaT.nerK.nporeKa3H oca.noKnocJienoBaTejiLHo odpadaTHBaeTCH npn 4° C pacTBopaMH cyjiBčpaTa - 4 - 3MM0HHH, KOTOpHe COflepjKST 0,05 MOJIb/jI TpHG, npií nOHOSIOIUeíí-ch KOHueHTpaiw (NH4)2soZj. H B ksehom GJiynae nyTe;i πητημη-HyTHoro nepeMeuiHBaHHH. Πρκ stom φθρΜθΗΤ Bce dojiBine pacTBopn-eTCH. TjiaBHaH wacca φθρΜθΗΤθ pacTBopneTCH b pauoHe. KOHupHTpa-Uiffl Mejxny 35 h 20 % HacwHHH pacTBopa cyjiL$aTa θμμοηηη.Φθρμθητ nepeocasnaeTCH nyTeM nodaBJíeHHH cynBroaTa θμμοηηη .noκοηθηηοη KOWHTpaiw b 50 %.CorjiacHO n3oópeTemro pememie 3a Han dnjio nocTurHyTo nyTeMΒΗΑθΛΘΗΚΗ (3-pepweHTa rn.npoKCíidyTKpaTnernnporeHa3H H3 uiTaM-Ma Pseudomonas putida. LlhraMM coxpaHHJin npenjviynecTBeHHo HadyjiLOHe c 2% arapoM NPN 4C τθμηοτθ b. KyjiLTHBHpoBaHnePseudomonas putida ocyinecTBJíHeTcn b cydMepcHOHHon xy clay Ty-PE Ha SH .HKOH MHHHMaJILHOH ΟρθΠθ nOCJie ΠβρβΟβΒΘΗΗΗ H3 ΠθρΒΗΗ-Hofi KyjiLTypti NPH TewnepaTypax .no 20 rpm (40 ° C npeHMynecTBenho NPN 30 ° C). BtipanHíBaHne corjiacHO Μ3θόρβτθΗΗΐο npoBO.nHJiocLHa τβχ HGTOHHHKax yrjiepo.na, NPN pacna.ne κοτορκχ odpa3yKTcn'aueToaueTaT h m .npoKcnóyTHpaT. There ηοτοηηιικθμη yrjiepo.naHBJIHIOTCH, HanpHMep, D, L -JIH3HH, D, L-JieHUHH, D, L-KapHHTHHH T., n. ot C4 .no Cjg B KanecTBeHCTOHHHKOB a30Ta npHMeHHJIHCL NH ^ Cl, H Π.Π. B ΤΘΧ cjiyHanx, b κοτορπχ hctohhhk yrjiepona ne μοι ςθτ nhtlhnnnnnnnnnnnnnnnnOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOCOC. óaKTepHH coónpaJincL, HanpHMep, rivet neHTpii $ yrapoBaHHH NPO-MHBaJIHCL φΟΟψθΤΗΗΜ oy ^ Η EPDM B 3aKJH0HeHHe npeBpanaJIHCL BdecKJieTOHHHH rpydtni SKCTpaKT · HanpHMep, rivet odpadoTKHyjrLTpa3ByxoM npn TewnepaTypax dJiH3KHX κ τοηκθ 3aMep3aHHH cnocJie.nyioiniíM neHTpHžyrHpoBaHHe m. Ηθχο.κηιιιηηοη b rpydoM skct-pact φβρΜθΗτ npoHBjmeT b 3aBHciLM0CTH ot ηοτοηηηκθ yrjieponanpHBe.neHHiie b Tadjinue I οπθιιηηηθοκηθ θκτηβηοοτη. C nOMOUfLK) mpaKHHOHHOrO OCazneHHH HJIH with 3KCTpawm cojlhmh, HanpHMep c cyjnHaTOM θμμοηηή, ocyinecTBJinTCH 10 - 15 KpaT — Hoe odoraneHne φθρΜθΗΤθ. Hjih stopo n, ejiecoodpa3HHM HBJíHeTcnpa3Be.neHHe dejnwBoro SKCTpaKTa c nocJienywiM ocasneHiieM no-naBJíHKinero KOJinnecTBa dejina 70% cyjn ^ aTOM θμμοηηη. nojman θκτηβηοοτβ ocraeTcn npn stom b οθ.κημθητθ. Azih HaJiB Hefiiiiero odoraneHKa-3-rHnpoKCHdyTHpaT.nerK.nporeKa3H oca.noKnocJienoBaTejiLHo odpadaTHBaeTCH npn 4C pacTBopaMH cyjiBčpaTa - 4 - 3MM0HHH, KOTOpHe COflepjKST 0.05 Mojib / her TpHG, NPTII nOHOSIOIUeíí KOHueHTpaiw-CH (NH 4) 2soZj. H B ksehom GJiynae nyTe; i πητημη-HyTHoro nepeMeuiHBaHHH. Πρκ stom φθρΜθΗΤ Bce dojiBine pacTBopn-eTCH. TjiaBHaH wacca φθρΜθΗΤθ pacTBopneTCH b pauoHe. KOHupHTpa-Uiffl Mejxny 35 h 20% HacwHHH pacTBopa cyji $ aTa θμμοηηη.Φθρμθητ nepeocasnaeTCH nyTeM nodaBJíHHH cynBroaTa θμμοηηη .noκοηθηηοη KOWHTpaiw b 50%.

Ha ΓΗηροφοόΗΟΜ HocHTejie, τθκομ κθκ, Hanpnwep, IO-KapdoKcn.ne-UHJK^apo3a, bo3mokho nanBHeninee odorameHHe φβρΜθΗτθ. lípustom Ha KOJioHKy, 3anojmeHHyío ΙΟ-κβρόοκοΗΟθφθροΒΟΗ, cajKaeT-gh φθρΜβΗΤ b 20 % HaowHHH pacTBopa cyjiB$aTa θμμοκιιη. IIOGJie npOMHBKH paCTBOpOM Ογ,ΗΒφθΤθ 3MM0HHH 3TOH ΗΘ ΚΟΗΒζθΗΤ-paiw npOH3BO.nHTCH φρθΚΙίΗΟΗΗΟβ SJHOKpOBaHUe G 17 % HaCWHHHpacTBopa cyjii^aTa θμμοηηη. B nepBoS mpaKiw HaóJnonaeTCH 4-xKpaTHoe h bo BTopoS - 7-mh xpaTHoe ποβηπιθηηθ cneHiKtaecKoSaKTHBHOCTH. Ancopdiw cnocoócTByioT cTpyKTyj^opMtfpyioiHHehohh, Tamie κοκ φοοφβτ, iwpaT H cyjiB$aT. IIonyHeHHHfi corjiac-HO H30ÓpGT6HHK) φβρΜβΗΤ XOpOUlO COXpaHHeTCH. HpH ΟΠΘίχηφΗΗΘΟΚΚΧaKTHBHOGTHX b 10 — 20 mojib/mhh/μγ denna noKa3HBaioTCH cjie-nywie MaKCHMaJiBHHe nyxepo.nHHe βκτηβηοοτη: an£KorojiB.nerHHporeHa3a ( I %Ha ΓΗηροφοόΗΟΜ HocHTejie, τθκομ κθκ, Hanpnwep, IO-KapdoKcn.ne-UHJK ^ apo3a, bo3mokho nanBHeninee odorameHHe φβρΜθΗτθ. lipustom Ha KOJioHKy, 3anojmeHHyío ΙΟ-κβρόοκοΗΟθφθροΒΟΗ, cajKaeT-gh φθρΜβΗΤ b 20% HaowHHH pacTBopa cyjiB $ aTa θμμοκιιη. IIOGJie npOMHBKH paCTBOpOM Ογ, ΗΒφθΤθ 3MM0HHH 3TOH ΗΘθΗΤ-paiw npOH3BO.nHTCH φρθΚΙίΗΟΗΗΟβ SJHOKpOBaHUe G 17% HaCWHHHpacTBopa cyjii ^ aTa θμμοηηη. B nepBoS mpaKiw HaoJnonaeTCH 4-xKpaTHoe h bo BTopoS - 7-mh xpaTHoe ποβηπιθηηθ cneHiKtaecKoSaKTHBHOCTH. Ancopdiw cnocoócTByioT cTpyKTyj ^ opMtfpyioiHHehohh, Tamie κοκ φοοφβτ, iwpaT H cyjiB $ aT. IIonyHeHHHfi corjiac-HO H30OpGT6HHK) φβρΜβΗΤ XOpOU10 COXpaHHeTCH. HpH ΟΠΘίχηφΗΗΘΟΚΚΧaKTHBHOGTHX b 10 - 20 mojib / mhh / μg denna noKa3HBaioTCH cjie-nywie MaKCHMaJiBHHe nyxepo.nHHe βκτηβηοοτη: an £ KorojiB.nerHHporeHa3a (I%

ManaT.nerH,nporeHa3a < 0,02 % jiaKTaTnerH.nporeHa3a <0,001%ManaT.nerH, nporeHa3a <0.02% jiaKTaTnerH.nporeHa3a <0.001%

Ha maře BapamíBaHaa daKTepnajiBHOH KyjiBTypu bbho.uho padoTaTBco cTyneHHaTHM ηθφιαιιιτοΜ KHCJiopo.na. H3odpeTeHHe. no.npodHee ποηοηηθτοη Ha cjie.nynueM npKMepe npo-BS.nSHKH BH.neJieHHH.Ha maře BapamíBaHaa daKTepnajiBHOH KyjiBTyp bbho.uho padoTaTBco cTyneHHaTHM ηθφιαιιιτοΜ KHCJiopo.na. H3odpeTeHHe. no.npodHee Ha cjie.nynueM npKMepe npo-BS.nSHKH BH.neJieHHH.

ΠρκΜθρ ocymecTBJíeHHH H3odpeTemiHΠρκΜθρ ocymecTBJíeHHH H3odpeTemiH

Pseudomonas putida (PpG 6) BHpaiííHBaeTCH b cydMepcKOHHoSKyjiBType b bgi.hkoh MHHHManBHOĚ cpe.ne. Cpe.na conepmiT Ha ηπτρ:6,97 K2HP04, 1,5 r NaH2P04, 0,2 Γ MgS04 . 7 H20, 7,5 ΜΓ PeS047 H20, 0,75 ΜΓ I'*mS04 . 4 H20, 0,75 ΜΓ ZnSO4 . 7 H2°» - 5 - 0,15 ΜΓ CuSO4 . 5 HgO, 0,15 ΜΓ CoC12 . 6 HgO H 0,15 ΜΓdopHOM KHCJIOTH. B nanecTBe πρμβηβοηηηχ nyjiLTyp cjiy^ma npe.nBapHTejiLHue ny-jn>Typtj, y κοτορκχ κ mí.bkoh mhhilmoJilhoh cpe.ne nodaBJíHjm 3kct-paKT .upereš (0,4 r/ji) h rJH0KO3y (10 γ/ji) . ITpH KyJIBTHBHpOBaHBH Ha D,L -KapHHTIÍHe nOCJie.HHHM .HOtíaBJIHJICHb KOHiieHTpaiíHE 2 γ/ji, κοκ θ.βηηοτβθηηβιη ηοτοηηηκ yrjie.po.ua na30Ta. Πρη KyjiLTUBiipoBaHun Ha npyrnx ηοτοήηκκθχ yrjiepo.ua(10 γ/ji) b KanecTBe ηοίόηηηκβ a30Ta npHMeHHJicn NH^Cl(3 γ/ji) . nocjie BHpamHBaHHH b τθηθηηθ 15 nacos óaKTepnH codn-pajiií HeHTpií$yriípoBaHiíeM, npoMBiBaJin MHoroKpaTHo φοοφβτΗΐΐΜóy$epoM (0,067 mojil/ji, pH = 7,5) n pa3pyuiajin b 3a'KJnoHeHHenocpe.ncTBOM oópadoTKH yjiLTpa3ByK0M npn 4° 0. PpytíHii decKJie-tohhhh θκοτρβκτ nojiynajin c noMOintio iíeHTpn$yrnpoBaHHH.Pseudomonas putida (PpG 6) BHpaiaHBaeTCH b cydMepcKOHHoSKyjiBType b bgi.hkoh MHHHManBHOE cpe.ne. Cpe.na conepmiT Ha ηπτρ: 6.97 K 2 HPO 4, 1.5 r NaH 2 PO 4, 0.2 Γ MgSO 4. 7 H20, 7.5 ΜΓ PeS047 H20, 0.75 ΜΓ I '* mS04. 4 H 2 O, 0.75 ΜΓ ZnSO 4. 7 H2 ° »- 5 - 0.15 ΜΓ CuSO 4. 5 HgO, 0.15 CoC12. 6 HgO H 0.15 ΜΓdopHOM KHCJIOTH. B nanecTBe πρμβηβοηηηχ nyjiLTyp cjiy ^ ma npe.nBapHTejiLHue ny-jn> Typetj, y κοτορκχ κ m.bhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhjhjhjhkk3y (10 γ / ji). ITpH KyJIBTHBHPOBaHBH Ha D, L -KHHHItHeNOCJie.HHHM .HHHMBJIHJICHb KOHiieHTpaiHE 2 γ / ji, κοκ θ.βηηοτβθηηβιη ηοτοηηηκ yrjie.po.ua to 30Ta. Πρη KyjiLTUBiipoBaHun Ha npyrnx ηοτοήηκκθχ yrjiepo.ua (10 γ / ji) b KanecTBe ηοίόηηηκβ and 30Ta npHMeHHJicn NH 2 Cl (3 γ / ji). nocjie BHpamHBaHHH b τθηθηηθ 15 nacos óaKTepnH CODN-pajiií HeHTpií yriípoBaHiíeM $, $ npoMBiBaJin MHoroKpaTHo φοοφβτΗΐΐΜóy EPDM (0.067 mojil / her, pH = 7.5) b n pa3pyuiajin 3a'KJnoHeHHenocpe.ncTBOM oópadoTKH yjiLTpa3ByK0M npn 0. 4 ° PpytíHii decKJie-tohhhh θκοτρβκτ nojiynajin c noMOintio iiTHTnnnnnnnnnnnhHHH.

Otot rpyóHH dejiKosaifí οκοτρθκτ pa3BO.nnJiH 0,067 mojil/ji φοοφθτ-hhm dyφepoM (pH 8) no ηοοτη&amp;θΗΗΗ KOHiieHTpaiiHH d.ejiKa b 5 -20 μγ/mji. no.naBjmwtf HacTL dejma ocajKuaJm npn 4° C H3 θτογο pacTBopacpe.ncTBOM nodaBJíeHHH cyjiLŽaTa θμμοηηη no 70 % HacLnneHHH. IIojiHaH aKTHBHOGTL 3-rHnpoKCHdyTHpaT.nerH.nporeHasH Haxo.niiTCHnpn 3tom b ocanne. IlocJie neHTpngĎyrnpoBaHKH ce.nHMeHT cycneH-nupoBajin npn 0° C b pacTBope cyjiL$aTa ομμοηηη (45 % Hacnme-hhh b 0,05 mojil/ji Tpnc) n nocjie θτογο chob3 neHTpnctjyrnpoBa-jih. B ce.niiMeHTe ocTaeTcn nojiHan θκτηβηοοτβ. Jpin naJiLHeíimeroodorameHHH ocTaroK nepeMeumBajiii no 5 miih. npn 4° C c paoTBO-paMH cyjiLcoaTa θμμοηηη co.nepHainne κθκηημ 0,05 mojil/ji Tpuc-HCI,pH 8 noHimaioinnxoH KOHiieKTpanitíi.Otot rpyóHH dejiKosaifí οκοτρθκτ pa3BO.nnJiH 0.067 mojil / ji φοοθτ-hhm dyφepoM (pH 8) no ηοοτη &amp; θΗΗΗ KOHiieHTpaiiHH d.ejiKa b 5 -20 μγ / mji. no.naBjmwtf HacTL dejma ocajKuaJm npn 4 ° C H3 θτογο pacTBopacpe.ncTBOM nodaBJiHHH cyjiLaTa θμμοηηη no 70% HacLnneHHH. IIojiHaH aKTHBHOGTL 3-rHnpoKCHdyTHpaT.nerH.nporeHasH Haxo.niiTCHnpn 3tom b ocanne. IlocJie neHTpngĎyrnpoBaHKH ce.nHMeHT cycneH-nupoBajin npn 0 ° C pacTBope cyjiL $ aTa ομμοηηη (45% Hacnme-hhh b 0,05 mojil / ji Tpnc) n nocjie θτογο chob3 neHTpnctjyrnpoBa-jih. B ce.niiMeHTe ocTaeTcn nojiHan θκτηβηοοτβ. Jpin naJiLHeíimeroodorameHHH ocTaroK nepeMeumBajiii no 5 miih. npn 4 [deg.] C. paoTBO-paMH cycloTa θμμοηηη co.nepHainne 0.05 mg / ml Tpuc-HCl, pH 8 noHimaioinnxoH KOHiOctpanite.

QepneHT pacTBopneTcn npn stom b B03pacTaK)iqefi Mepe, npeiiMy-mecTBeHHO b pafione KOHpeHTpannn Mesny 35 n 20 / HacwHiiHcyjiLcpaTOM θμμοηι-ιη (cm. Tadjinny 2). - 6 - Φθρ^θητ nepe oca^na jih CHOBa nocpe.ncTBOM .nodaBJíeHHH cyjiLinaTa3MM0HHH .no ΚΟΗΘΗΗΟΜ ΚΟΗΙξθΗΤρθΙΧΗΗ B 50 % HaCHlUeHHH.QepneHT pacTBopneTcn npn stom b B03pacTaK) iqefi Mepe, npeiiMy-mecTBeHHO b pafione KOHpeHTpannn Mesny 35 n 20 / HacwHiiHcyjiLcpaTOM θμμοηι-ιη (cm. Tadjinny 2). - 6 - Φθρ ^ θητ nepe oca ^ south CHOB nocc.ncTBOM .nodaBJiHHH cyjiLinaTa3MM0HHH .no ΚΟΗΘΗΗΟΜ ΚΟΗΙξθΗΤρθΙΧΗΗ B 50% HaCHlUeHHH.

IlocJie iieHTpnroyriipoBaHiw cpepMeHT cycneHnupoBajm b 3,2 mojib/jipacTBopa cyjiB$aTa θμμοηηη, pH 7, h coxpaHHJiH npn 4° C. JUfl najiLHéHiiiero odorainemra I mji pacTBopa $epweHTa b cyjiLcpaTeθμμοηηη 20 % HacHineHKH caJKajm Ha 2-x mji kojiohky c IO-napdo-Kcnce$apo3oií; cneiyičpKHecKaH θκτηβηοοτβ οοοτοβλήθτ II mojib/μηη/μγ dejiKa; oóiuhh dejioK - 1,5 μγ. HojmaH θκτηβηοοτβ οοτθθτch Ha HOGHTejie. Ilocjie προμηβθηηη 10 mji pacTBopa cyjitčpaTa aM-mohhh (20 % HactimeHEH) Ha KOJiOHKy no.naBaJHi nccJienoBaTejiLHOno 2 mji pacTBopa cyjrBípaTa θμμοηηη (17 % ηθοητιιθηηη) . B noJiy-ΗΘΗΗΗΧ ,HByX φρθΚΗΗΗΧ HaXO.nHTCH BCH 3KTIÍBHOCTB, HO TOJILKO25 % dejina. ΟπβΗΗφΗΗΘΟΚΘΗ aKTHBHOCTB COCTaBJIHOT B I φρθΚΙξΗΗ 41 MOJIB/μηη/μγ dejma (0,3 μγ dejma) h bo 2 φρθκκΗΗ - 80 mojib/mhh/μγ dsjína (0,1 μγ dejma).IlocJie iieHTpnroyriipoBaHiw cpepMeHT cycneHnupoBajm Mojib 3.2 b / jipacTBopa cyjiB $ aTa θμμοηηη pH 7 h coxpaHHJiH npn 4 ° C JUfl najiLHéHiiiero odorainemra I np pacTBopa $ epweHTa b cyjiLcpaTeθμμοηηη 20% HacHineHKH caJKajm Ha 2 x np kojiohky with Pd-C IO -Kcnce $ apo3oii; cneiyičpKHecKaH θκτηβηοοτβ οοοτοβλήθτ II mojib / μηη / μγ dejiKa; oóiuhh dejioK - 1.5 μγ. HojmaH θκτηβηοοτβ οοτθθτch Ha HOGHTejie. Ilocjie προμηβθηηη 10 mji pacTBopa cyjitčpaTa aM-mohhh (20% HactimeHEH) Ha KOJiOHKy no.naBaJHi nccJienoBaTejiLHOno 2 mji pacTBopa cyjBBpaTa θμμοηηη (17% ηθοητιιθηηη). B noJiy-ΗΘΗΗΗΧ, HByX φρθΚΗΗΗΧ HaXO.nHTCH BCH 3KTIÍBHOCTB, HO TOJILKO25% history. KTπβΗΗφΗΗΘΟΚΘΗ aKTHBHOCTB COCTaBJIHOT B I ΗΗρθΚΙξΗΗ 41 MOJIB / μηη / μγ dejm (0,3 μγ dejm) h bo 2 φρθκκΗΗ - 80 mojib / mhh / μγ dsjína (0,1 μγ dejma).

CycneH3HH ^epweHTa coxpaHseMU b HacwHHOM pacTBope cyjiBfóaTaθμμοηηη. Ilocjie 6 μθοηιϊθβ coxpaHeHHH npn TeMnepaTypax okojio4° C noTepn aKTHBHOCTH 3-rHnpoKCHtíyTHpaT.nerHnporeHa3H HeHadJHonajiact. - 7 -CycneH3HH ^ epweHTa coxpaHseMU b HacwHHOM pacTBope cyjiBfaaTaθμμοηηη. Ilocjie 6 μθοηιϊθβ coxpaHeHHH npn TeMnepaTypax okojio4 ° C noTepn aKTHBHOCTH 3-rHnpoKCHTyTHpaT.nerHnporeHa3H HeHadJHonajiact. - 7 -

Tatíjixua ITatijixua I

ΟπβΙίΚφΚΉΘΟΚΘΗ aKTHBHOCTB δ-ΓΗΙίρΟΚΟΗόγΤΗρεΤ,ΙίθΓΗ.ΙίρΟΓΘΗΘδΗ B rpydhix SKGTpaKTax H3 Pseudomonas putida nocuie pocTa Ha aHeToaueTaTodpa3ynwx cydcTpaTax .ujih KyjiL- THBHpOBaHHflKTπβΙίΚφΚΉΘΟΚΘΗ aKTHBHOCTB δ-ΓΗΙίρΟΚΟΗόγΤΗρεΤ, ΙίθΓΗ.ΙίρΟΓΘΗΘδΗ B rpydhix SKGTpaKTax H3 Pseudomonas putida nocuie pocTa Ha aHeToaueTaTodpa3ynwx cydcTpaTax .ujih KyjiL- THBHpOBaHHfl

Mctohhhk yrjiepo.na S-rHupoKCHdyTHpaT.nerHuporeHa 3H mojil/mhh/μγ dejiKa D,L- rKupoKCHdyTHpaT 3,5 D,L- KapHHTHH 2,0 D,L- jieínw 3,6 D,L- JUÍ3HH 0,8 - 8 -Mctohhhk yrjiepo.na S-rHupoKCHdyTHpaT.nerHuporeHa 3H mojil / mhh / μγ dejaKa D, L- rKupoKCHdyTHpaT 3,5 D, L- KapHHTHH 2,0 D, L-jinw 3,6 D, L- JUI3HH 0,8 - 8 -

TaÓJinua 2 Οήηοτκθ 3-rH.npoKCHdyTHpaT.nerHi];poreHa3H (cydcTpaT .wKyjiBTHBiípoBaHiiH D,L -κθρβήτεη) H3 Pseudomonas putidanojiyHeHiie npoBo.wiH H3 17 mji rpydoro sxcTpaKTa (7,5 μγ/mjidejixa).TaÓJinua 2 Οήηοτκθ 3-rH.npoKCHdyTHpaT.nerHi]; poreHa3H (cydcTpaT .wKyjiBTHBiípoBaHiiH D, L-κερβήτεη) H3 17 mji rpydoro sxcTpaKTa (7.5 μγ / mjidejixa).

Oca.noK nocJie odpadoTKH 45 % cyjn>$aTOM θμμοηκη, odpadaTHBaJica:noojie.noBaTejiBHo 5-k> mji pacTBopa cyjn>$aTa θμιλοηηη nomuKawix-CH KOHUeHTpanHH. 0 = ocaupK,’ H = Ha.iíoca.iíOHHaH wekoctlOko.noK noct wasteTKH 45% cyjn> $ aTOM θμμοηκη, odpadaTHBaJica: noojie.noBaTejiBHo 5-k> mji pacTBopa cyjn> $ aTa θμιλοηηη nomuKawix-CH KOHUeHTpanHH. 0 = ocaupK, H = H, and HOH and H wecoct

Odiwi dejioK Odiw aKTHBHOGTB CneiíH$ircecKafl aKTZBHOCTB OniicTKa(-pa3) Bhxou w (μγ) ( mojil/meh) ( μολβ/μηη/μγ) rpydtm 3KCTpaKT 228 470 2,06 - 0 70 % 202 490 2,3 1,1 H 45 % (I) 2,6 H 45 % (2) 3,2 H 35 $ 2,6 H 33 $ 4,2 H 30 % 58 H 27 % 7 136 19 9,2 29 H 25 % 8 160 20 9,7 34 - 9 -Odiwi dejioK Odiw aKTHBHOGTB CneiH $ ircecKafl aKTZBHOCTB OniicTKa (-pa3) Bhxou w (μγ) (mojil / meh) (μολβ / μηη / μγ) rpydtm 3KCTpaKT 228 470 2.06 - 0 70% 202 490 2.3 1.1 H 45% (I) 2.6 H 45% (2) 3.2 H 35 $ 2.6 H 33 $ 4.2 H 30% 58 H 27% 7 136 19 9.2 29 H 25% 8 160 20 9 , 7 34 - 9 -

Tataua H 22 %7,5 H 19 % l ' (npO.HOJWHHe) 102 34 14 6,8 . 22 -Μ-Tataua H 22% 7.5H 19% 1 '(npO.HOJWHHe) 102 34 14 6.8. 22 -Μ-

SOBOTA H30EPETEHMH 1. Cnocod nojiyzeHzn 3-rznpoKCzdyTHpaTnerznporeHa3H xa-OTnzzaJomzfícH τθμ, ζτο BHpamzBaeTcn ιιιτθμμ Psuedomonas putidaz πρκΜθΗΗίοτοίΐ ts zctozhzkz yrjiepo.na, npz pacna.ne κοτορζχ od-pa3yioTGB aneToaneTaT z rznpozczdyTZpaT. 2. Cnocod no nyHKTy I . oTJiEzawzcH τθμ, zto ιιιτθμμPseudomonas putida BLipaiiíZBacTcn npz TeMnepsTypax ot 20 .no40° C b cydMepczoHHofi zyjiBType b ztz.nzofi mzhzmsjibhoz cpene.Hocjie BpeweHZ BbipaiuzBaHZH b 5 - 40 zscob, tíazTepzz OT.nejiH-íotch, nepeBO.UHTCH e deozjieTozmiz denzoBtiz θκοτρθκτ, Z3 koto-poro φθρΜθΗΤ BÍJHeJIHeTOH nOCpe.nCTBOM φρθΚΙίΚΟΗΗΟΓΟ OCaJKUeHHHcyjiB$aTa ομμοηζη z b cjiyzae Heodxo.nzMOCTZ nonsepraeTCH ozzct-tze zjiz odorameHZio. 3. Cnocod no nyHKTaM I z 2 o Tanzanii ech tom, zto b zazecTBe zctozhzkob yrjiepo.na, npz pacna.ne κοτορπχ odpa3yioT-cn aneToaneTaT z rznpoKczdyTzpaT, npzMeHEJizcB D»L -jreznZH,.D,L-jiz3HH,D,L - KapHZTZH, Hepa3BeTBJieHHtie yrjieBO.nopo.ZH cZjixhoz nenz ot Cg no CjQ z JKZpHtie kzczoth - ot C^ no Cjg. 4. Cnocod no nyHKTaM I z 3 OTHHzaramziícH τθμ, zto Z3rpydoro deczjieTOZHoro SKCTpazTa tojibko nocpencT3OM φρβκηζοΗ-ηογο ocasnenzn cyjiB$aTa aMMOHzn nojiyzeH φθρΜβκτ co cnenz^z-zecKOH θκτζβηοοτβ b 10 - 20 mojib/μζη/μγ dejiza. 5. Cnocod no nyHKTaM I z 4 OTJizzaioinHzcH τβΜ, ζτο odo-raiueHze φβρΜθΗτθ ocyiyecTBjLHeTCH xpoMaTorpa$zzecKH Ha rznpo-$odHOM HoczTejie, ískom Kaz I0-zapdozczneiiHJice$apo3a zjhino.nodHOM. 6. Cnocod no nyHKTy 5 . othzzsioiukzch Ter.i, zto $epMeHTnpz bhcokzx KOHneHTpanzHX cyzB^aTa, cóoc$aTa zjiz nzTpaTaancopdzpyeTCH, a npz cHZ&amp;aiaitHXCH KOHneHTpanzHX stzx zohob' - sjnonpyeTCH. -441 - 7. Cnocoó no nyHKTSM I h 3 OTJiKnaiomKHCfl τθμ, ητο bnpoiíecce BNpamHBaHHH óaKTepmí πρΗΜβΗηθτοη nocTyneiraaTHfi .neφηΐίΗτ KHCJiopo.ua.Saturday H30EPETEHMH first Cnocod nojiyzeHzn rznpoKCzdyTHpaTnerznporeHa3H 3-x-OTnzzaJomzfícH τθμ, ζτο BHpamzBaeTcn ιιιτθμμ Psuedomonas putidaz πρκΜθΗΗίοτοίΐ ts zctozhzkz yrjiepo.na, HPH-pacna.ne κοτορζχ from pa3yioTGB aneToaneTaT from rznpozczdyTZpaT. 2. Cnocod no nyHKTy I. oTJiEzawzcH τθμ, ZTO ιιιτθμμPseudomonas putida BLipaiiíZBacTcn HPH TeMnepsTypax .no40 rpm 20 ° C b b cydMepczoHHofi zyjiBType ztz.nzofi mzhzmsjibhoz cpene.Hocjie BpeweHZ BbipaiuzBaHZH b 5-40 zscob, tíazTepzz OT.nejiH-íotch, nepeBO.UHTCH e deozjieTozmiz denzoBtiz θκοτρθκτ Z3 koto-poro φθρΜθΗΤ BÍJHeJIHeTOH nOCpe.nCTBOM φρθΚΙίΚΟΗΗΟΓΟ OCaJKUeHHHcyjiB $ aTa ομμοηζη zb cjiyzae Heodxo.nzMOCTZ nonsepraeTCH ozzct-tze zizameHZio. 3. Cnocod no nyHKTaM I z 2 o Tanzania ech tom, zto b zazecTBe zctozhzkob yrjiepo.na, npz pacna. - KapHZTZH, Hepa3BeTBJieHHtie yrjieBO.nopo.ZH cZjixhoz nenz ot Cg no CjQ z JKZpHtie kzczoth - ot C ^ no Cjg. 4. Cnocod no nyHKTaM I z 3 OTHHhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhnmhmnmnnnmnnnmnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn in the European Applicant. 5. Cnocod no nyHKTaM I of 4 OTJizzaioinHzcH τβΜ, ζτο odo-raiueHze φβρΜθΗτθ ocyiyecTBjLHeTCH xpoMaTorpa $ zzecKH Ha rznpo- $ odHOM HoczTejie Kaz I0-zapdozczneiiHJice $ apo3a zjhino.nodHOM. 6. Cnocod no nyHKTy 5. othzzsioiukzch Ter.i, zto $ epMeHTnpz bhcokzx KOHneHTpanzHX cyzB ^ aTa, coc $ aTa zzppaTaancopdzpyeTCH, a npz cHZ &amp; aiaitHXCH KOHneHTpanzHX stzx zohob '- sjnonpyeTCH. -441 - 7. Cnocoó no nyHKTSM I h 3 OTJiKnaiomKHCfl τθμ, ητο bnpoiíecce BNpamHBaHHH aaKTepmí πρΗΜβΗηθτοη nocTyneiraaTHfi .neφηΐίΗτ KHCJiopo.ua.

AHHOTMW I430ÓpeTeHne KacaeTcn cnocoóa nojiyveiwi 3~rHnpoKCHóyTHpaT.neri<[nporeHa3H.AHHOTMW I430ÓpeTeH KacaeTcn cnocoóa nojiyveiwi 3 ~ rHnpoKCHoYTHpaT.neri <[nporeHa3H.

HeJIL H30ÓpSTSHHH GOGTOHT B Πρθ,ηΠΟ&amp;ΘΗΙΙΗ HH3KOCTOHMOCTHOIO MG—To.ua, KOTopuii ηθθτ bosmojkiioctl nojiynaTB φΘρΜβΗΤ g bhcokoécner^BHecKOĚ θκτηβηοοτβιο. 3a.naHa ooGTosuia b nojiyneHHH acejiaeMoro $epweHTa nocpe.ncTBOMBbipaimiBaHiíH ηοβογο ÓaKTepjaaJiLHoro niTawa Ha cyócTpaTax nn&amp;KyjILTHBHpOBaHHH, .no CHX ΠΟρ Ηθ ΠρΗΜΘΗΗβΜΗΧ.HeJIL H30ÓpSTSHHH GOGTOHT B Πρθ, ηΠΟ & HH3KOCTOHMOCTHOIO MG—To.ua, KOTopuii ηθθτ bosmojkiioctl nojiynaTB φΘρΜβΗΤ g bhcokoécner ^ BHecKOĚ θκτηβηοοτβιο. 3a.naHa ooGTosuia b nojiyneHHH acejiaeMoro $ epweHTa nocpe.ncTBOMBbipaimiBaHiíH ηοβογο ÓaKTepjaaJiLHoro niTawa Ha cyócTpaTax nn & KyjILTHBHpOBaHHH, .no CHX ΠΟρ Ηθ ΠρΗΜΘΗΗβΜΗΧ.

CyuíHOCTL H3oópeTeHHH goctoht b tom, hto hitsmm Pseudomonaaputida BHpaumBajm Ha τθχ cyócTpaTax, npn pacna.ne κοτορπχB03HHKaioT aneToaneTaT hjih rH.npoKCHÓyTHpaT, hjih sce Ha cyócT-paTax H3 Hepa3BeTBJieHHHX - οτ Οθ no Cjq - yrjieBO.nopo.noB.CyuíHOCTL H3oópeTeHHH goctoht b that HTO hitsmm Pseudomonaaputida BHpaumBajm Ha τθχ cyócTpaTax, NPN pacna.ne κοτορπχB03HHKaioT aneToaneTaT hjih rH.npoKCHÓyTHpaT, hjih SCE cyócTpaTax Ha H3 Hepa3BeTBJieHHHX - οτ Οθ well Cjq - yrjieBO.nopo.noB.

Claims (4)

4$ Předmět vynálezu L. Způsob přípravy 3-hydroxybutyrátdehydrogenázy,vyznačující se tlm, že se kultivuje kmen Pseudomonas putidaa používají se takové zdroje uhlíku, při jejichž rozpadu setvoří acetoacetát a hydroxybutyrát.SUMMARY OF THE INVENTION L. Process for the preparation of 3-hydroxybutyrate dehydrogenase, characterized in that the Pseudomonas putidaa strain is cultured using carbon sources to decompose acetoacetate and hydroxybutyrate. 2. Způsob podle bodu 1, vyznačující se tím, že se kmenPseudomonas putida kultivuje při teplotách od 20 do 40 °Cv submerzní kultuře v kapalném minimálním mediu, po kultivacitrvající 5 až 40 hodin se bakterie oddělí, převedou na bezbu-něčný bilkovinový extkakt, ze kterého se ferment oddělí frak-čním srážením sulfátem amonným a v případě potřeby se čistí nebo obohacuje· ' ' ' ' ' .·' 'AS 3· Způsob podle bodů 1 a 2, vyznačující se tím, že sejako zdroje uhlíku, při jejichž rozpadu se tvoří acetoacetáta hydroxybutyrát se používají D,L-leucia, D,l-lysin, D,L-kar-nitin, nerozvětvené uhlovodíky s délkou řetězce 6 až 10 atomůuhlíku a mastné kyseliny od čtyč do šestnácti atomů uhlíku.2. The method of claim 1, wherein the Pseudomonas putida strain is cultured at temperatures of from about 20 DEG C. to about 40 DEG C. in a submerged culture in a liquid minimal medium, the bacteria are separated after 5 to 40 hours of cultivation, converted into a cell free proteinaceous extact. wherein the ferment is separated by fractional precipitation with ammonium sulphate and, if necessary, purified or enriched in the AS 3 process. the hydroxybutyrate acetoacetate forms D, L-leucia, D, 1-lysine, D, L-carnitine, straight chain hydrocarbons having from 6 to 10 carbon atoms, and fatty acids from 4 to 16 carbon atoms. ' A*·'A * · 4. Způsob podle bodů 1 a 3, vyznačující se tím, že se zhrubého bezbuněčného extraktu pouhým frakčním srážením sulfátemamonným získá ferment se specifickou aktivitou 10 až 20 mol//min/ mg bílkoviny. 5· Způsob podle bodů 1 a 4, vyznačující se tím, že seobohacení fermentu provádí chromatograficky na hydrofobnímnosiči jako je 10-karboxydecylcefaroza.4. The process of claim 1 wherein the coarse cell-free extract is merely fractionated by sulphate-ammonium fractionation to obtain a ferment with a specific activity of 10-20 mol / min / mg protein. 5. The process of claim 1, wherein the fermentation is effected chromatographically on a hydrophobic carrier such as 10-carboxydecylcepharose. - Λ* &amp;. Způsob podle bodu 5, vyznačující se tím, že se fermentpři vysokých koncentracích sulfátu, fosfátu nebo citrátuadsorbuje a při poklesu těchto koncentrací se evuuje. ,'x- & * &amp;. 5. The process of claim 5 wherein the high concentration of sulfate, phosphate, or citrate is adsorbed and evolves when such concentrations are decreased. , 'x 7. Způsob podle bodů 1 až 3, vyznačující se tím, že sepři kultivaci bakterií používá stupňovitého deficitu kyslíku, Uznáno vynálezem na základě výsledků expertizy, provedenéÚřadem pro vynálezectví a patentnictví, Berlín, DD7. A method according to any one of claims 1 to 3, wherein the cultivation of the bacteria utilizes a stepped oxygen deficiency, recognized by the invention based on the results of an expert's review by the Office of Invention and Patenting, Berlin, DD.
CS8981A 1980-03-31 1981-01-05 Method of 3-hydroxybutyratedehydrogenase preparation CS233318B1 (en)

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