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WO1999066028A3 - Genes for the biosynthesis of epothilones - Google Patents

Genes for the biosynthesis of epothilones Download PDF

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Publication number
WO1999066028A3
WO1999066028A3 PCT/EP1999/004171 EP9904171W WO9966028A3 WO 1999066028 A3 WO1999066028 A3 WO 1999066028A3 EP 9904171 W EP9904171 W EP 9904171W WO 9966028 A3 WO9966028 A3 WO 9966028A3
Authority
WO
WIPO (PCT)
Prior art keywords
epothilone
biosynthesis
genes
epothilones
cancer
Prior art date
Application number
PCT/EP1999/004171
Other languages
French (fr)
Other versions
WO1999066028A2 (en
Inventor
Thomas Schupp
James Madison Ligon
Istvan Molnar
Ross Zirkle
Joern Goerlach
Devon Cyr
Original Assignee
Novartis Ag
Novartis Erfind Verwalt Gmbh
Thomas Schupp
James Madison Ligon
Istvan Molnar
Ross Zirkle
Joern Goerlach
Devon Cyr
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to NZ508326A priority Critical patent/NZ508326A/en
Priority to CA002329774A priority patent/CA2329774A1/en
Priority to AU46116/99A priority patent/AU753567B2/en
Priority to IL13973599A priority patent/IL139735A0/en
Priority to HU0102186A priority patent/HUP0102186A3/en
Priority to BR9911349-0A priority patent/BR9911349A/en
Priority to PL345579A priority patent/PL200157B1/en
Priority to SK1924-2000A priority patent/SK19242000A3/en
Priority to EP99929243A priority patent/EP1088078A2/en
Priority to JP2000554837A priority patent/JP2002518004A/en
Application filed by Novartis Ag, Novartis Erfind Verwalt Gmbh, Thomas Schupp, James Madison Ligon, Istvan Molnar, Ross Zirkle, Joern Goerlach, Devon Cyr filed Critical Novartis Ag
Publication of WO1999066028A2 publication Critical patent/WO1999066028A2/en
Publication of WO1999066028A3 publication Critical patent/WO1999066028A3/en
Priority to IL139735A priority patent/IL139735A/en
Priority to NO20006195A priority patent/NO20006195L/en
Priority to IL190391A priority patent/IL190391A0/en
Priority to NO20091055A priority patent/NO20091055L/en

Links

Classifications

    • 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52Genes encoding for enzymes or proenzymes
    • 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
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation 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
    • C12P17/181Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Nucleic acid molecules are isolated from Sorangium cellulosum that encode polypeptides necessary for the biosynthesis of epothilone. Disclosed are methods for the production of epothilone in recombinant hosts transformed with the genes of the invention. In this manner, epothilone can be produced in quantities large enough to enable their purification and use in pharmaceutical formulations such as those for the treatment of cancer.
PCT/EP1999/004171 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones WO1999066028A2 (en)

Priority Applications (14)

Application Number Priority Date Filing Date Title
NZ508326A NZ508326A (en) 1998-06-18 1998-06-12 A polyketide synthase and non ribosomal peptide synthase genes, isolated from a myxobacterium, necessary for synthesis of epothiones A and B
SK1924-2000A SK19242000A3 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
IL13973599A IL139735A0 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
HU0102186A HUP0102186A3 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
BR9911349-0A BR9911349A (en) 1998-06-18 1999-06-16 Genes for epothilone biosynthesis
PL345579A PL200157B1 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
EP99929243A EP1088078A2 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
CA002329774A CA2329774A1 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
JP2000554837A JP2002518004A (en) 1998-06-18 1999-06-16 Epothilone biosynthesis gene
AU46116/99A AU753567B2 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones
IL139735A IL139735A (en) 1998-06-18 2000-11-16 Genes for the biosynthesis of epothilones
NO20006195A NO20006195L (en) 1998-06-18 2000-12-06 Genes for the biosynthesis of epothilones
IL190391A IL190391A0 (en) 1998-06-18 2008-03-24 Genes for the biosynthesis of epothilones
NO20091055A NO20091055L (en) 1998-06-18 2009-03-09 Genes for the biosynthesis of epothilones

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US9950498A 1998-06-18 1998-06-18
US09/099,504 1998-06-18
US10163198P 1998-09-24 1998-09-24
US60/101,631 1998-09-24
US11890699P 1999-02-05 1999-02-05
US60/118,906 1999-02-05

Publications (2)

Publication Number Publication Date
WO1999066028A2 WO1999066028A2 (en) 1999-12-23
WO1999066028A3 true WO1999066028A3 (en) 2000-06-29

Family

ID=27378840

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/004171 WO1999066028A2 (en) 1998-06-18 1999-06-16 Genes for the biosynthesis of epothilones

Country Status (16)

Country Link
EP (1) EP1088078A2 (en)
JP (3) JP2002518004A (en)
KR (1) KR100511233B1 (en)
CN (1) CN100374565C (en)
AU (1) AU753567B2 (en)
BR (1) BR9911349A (en)
CA (1) CA2329774A1 (en)
HU (1) HUP0102186A3 (en)
ID (1) ID29128A (en)
IL (3) IL139735A0 (en)
NO (2) NO20006195L (en)
NZ (1) NZ508326A (en)
PL (1) PL200157B1 (en)
SK (1) SK19242000A3 (en)
TR (1) TR200003759T2 (en)
WO (1) WO1999066028A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849651B2 (en) 1996-12-03 2005-02-01 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6965034B2 (en) 1996-12-03 2005-11-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2775187B1 (en) 1998-02-25 2003-02-21 Novartis Ag USE OF EPOTHILONE B FOR THE MANUFACTURE OF AN ANTIPROLIFERATIVE PHARMACEUTICAL PREPARATION AND A COMPOSITION COMPRISING EPOTHILONE B AS AN IN VIVO ANTIPROLIFERATIVE AGENT
DE19846493A1 (en) * 1998-10-09 2000-04-13 Biotechnolog Forschung Gmbh DNA sequence coding for products involved in the biosynthesis of polyketide or heteropolyketide compounds, especially epothilone
US6410301B1 (en) 1998-11-20 2002-06-25 Kosan Biosciences, Inc. Myxococcus host cells for the production of epothilones
IL143069A0 (en) 1998-11-20 2002-04-21 Kosan Biosciences Inc Recombinant methods and materials for producing epothilone and epothilone derivatives
WO2001053533A2 (en) * 2000-01-21 2001-07-26 Kosan Biosciences, Inc. Method for cloning polyketide synthase genes
NZ521788A (en) * 2000-04-28 2007-04-27 Kosan Biosciences Inc Production of polyketides
US6998256B2 (en) 2000-04-28 2006-02-14 Kosan Biosciences, Inc. Methods of obtaining epothilone D using crystallization and /or by the culture of cells in the presence of methyl oleate
US7257562B2 (en) 2000-10-13 2007-08-14 Thallion Pharmaceuticals Inc. High throughput method for discovery of gene clusters
JP2005500974A (en) 2000-10-13 2005-01-13 ザ ユニバーシテイ オブ ミシシッピー Synthesis of epothilones and related analogues
ES2337134T3 (en) 2002-03-12 2010-04-21 Bristol-Myers Squibb Company DERIVATIVES OF C3-CIANO-EPOTILONE.
US7767399B2 (en) * 2005-01-31 2010-08-03 Merck & Co., Inc. Purification process for plasmid DNA
JP2014508516A (en) 2011-01-28 2014-04-10 アミリス, インコーポレイテッド Screening of microcolonies encapsulated in gel
JP2014519028A (en) 2011-05-13 2014-08-07 アミリス, インコーポレイテッド Methods and compositions for detecting microbial production of water immiscible compounds (WIC)
US10927382B2 (en) 2012-08-07 2021-02-23 Amyris, Inc. Methods for stabilizing production of acetyl-coenzyme a derived compounds
WO2014144135A2 (en) 2013-03-15 2014-09-18 Amyris, Inc. Use of phosphoketolase and phosphotransacetylase for production of acetyl-coenzyme a derived compounds
WO2015020649A1 (en) 2013-08-07 2015-02-12 Amyris, Inc. Methods for stabilizing production of acetyl-coenzyme a derived compounds
US10808015B2 (en) 2015-06-25 2020-10-20 Amyris, Inc. Maltose dependent degrons, maltose-responsive promoters, stabilization constructs, and their use in production of non-catabolic compounds
CN106916834B (en) * 2015-12-24 2022-08-05 武汉合生科技有限公司 Biosynthetic gene cluster of compounds and application thereof
CN111138444B (en) * 2020-01-08 2022-05-03 山东大学 Epothilone B glucoside compounds and enzymatic preparation and application thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998022461A1 (en) * 1996-11-18 1998-05-28 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone c, d, e and f, production process, and their use as cytostatic as well as phytosanitary agents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998022461A1 (en) * 1996-11-18 1998-05-28 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone c, d, e and f, production process, and their use as cytostatic as well as phytosanitary agents

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MOLNAR I. ET AL.: "The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90", CHEM. BIOL., vol. 7, 2000, pages 97 - 109, XP000904734 *
SCHUPP T. ET AL.: "A Sorangium cellulosum (myxobacterium) gene cluster for the biosysnthesis of the macrolide antibiotic soraphen A: cloning, characterization and homology to polyketide synthase genes from actinomycetes", J. BACTERIOL., vol. 177, no. 13, 1995, pages 3673 - 3679, XP000893003 *
TANG LI, ET AL.: "Cloning and heterologous expression of the epothilone gene cluster.", SCIENCE, vol. 287, 28 January 2000 (2000-01-28), pages 640 - 642, XP002135841 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6849651B2 (en) 1996-12-03 2005-02-01 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6965034B2 (en) 1996-12-03 2005-11-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6972335B2 (en) 1996-12-03 2005-12-06 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof

Also Published As

Publication number Publication date
NO20091055L (en) 2001-02-16
SK19242000A3 (en) 2001-07-10
TR200003759T2 (en) 2001-06-21
JP2008092958A (en) 2008-04-24
PL345579A1 (en) 2001-12-17
HUP0102186A3 (en) 2005-10-28
CN100374565C (en) 2008-03-12
AU753567B2 (en) 2002-10-24
EP1088078A2 (en) 2001-04-04
HUP0102186A2 (en) 2001-10-28
IL190391A0 (en) 2008-11-03
JP2006061166A (en) 2006-03-09
BR9911349A (en) 2001-03-13
KR20010052962A (en) 2001-06-25
KR100511233B1 (en) 2005-08-31
IL139735A (en) 2009-06-15
NO20006195D0 (en) 2000-12-06
WO1999066028A2 (en) 1999-12-23
NZ508326A (en) 2003-10-31
NO20006195L (en) 2001-02-16
PL200157B1 (en) 2008-12-31
CN1305530A (en) 2001-07-25
IL139735A0 (en) 2002-02-10
ID29128A (en) 2001-08-02
CA2329774A1 (en) 1999-12-23
AU4611699A (en) 2000-01-05
JP2002518004A (en) 2002-06-25

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