WO2008096021A3 - Proceso para la producción en continuo de lovastatina - Google Patents
Proceso para la producción en continuo de lovastatina Download PDFInfo
- Publication number
- WO2008096021A3 WO2008096021A3 PCT/ES2007/000389 ES2007000389W WO2008096021A3 WO 2008096021 A3 WO2008096021 A3 WO 2008096021A3 ES 2007000389 W ES2007000389 W ES 2007000389W WO 2008096021 A3 WO2008096021 A3 WO 2008096021A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lovastatine
- production
- continuous
- continuous production
- fluidized bed
- Prior art date
Links
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 title abstract 5
- 238000010924 continuous production Methods 0.000 title abstract 3
- 238000000034 method Methods 0.000 title abstract 3
- 238000000855 fermentation Methods 0.000 abstract 2
- 230000004151 fermentation Effects 0.000 abstract 2
- 230000005764 inhibitory process Effects 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 2
- 241001465318 Aspergillus terreus Species 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000000605 extraction Methods 0.000 abstract 1
- 239000007789 gas Substances 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 239000008188 pellet Substances 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Proceso para la producción en continuo de lovastatina. La presente invención consiste en la producción de lovastatina, a partir de cultivos de Aspergillus terreus en forma de pellets, mediante un proceso de fermentación en continuo en un biorreactor de tipo columna de burbujeo operando de forma análoga a un biorreactor de lecho fluidizado (BLF) con un cultivo en tres fases, gas, liquido y sólido. La producción de lovastatina está regulada mediante un mecanismo de inhibición por producto, dando lugar al cese de la síntesis cuando la concentración alcanza un determinado valor. El proceso permite la obtención en continuo de un caldo de fermentación libre de biomasa conteniendo éste la lovastatina, lo cual facilita las posteriores etapas de extracción y purificación. La operación en continuo da lugar a que parte de la lovastatina generada abandone el biorreactor de lecho fluidizado, disminuyendo de esta forma los efectos de la inhibición por producto.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200700519A ES2319029B1 (es) | 2007-02-09 | 2007-02-09 | Proceso para la produccion en continuo de lovastatina. |
| ESP200700519 | 2007-02-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2008096021A2 WO2008096021A2 (es) | 2008-08-14 |
| WO2008096021A3 true WO2008096021A3 (es) | 2008-09-25 |
Family
ID=39682153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/ES2007/000389 WO2008096021A2 (es) | 2007-02-09 | 2007-06-08 | Proceso para la producción en continuo de lovastatina |
Country Status (2)
| Country | Link |
|---|---|
| ES (1) | ES2319029B1 (es) |
| WO (1) | WO2008096021A2 (es) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4231938A (en) * | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| US4294926A (en) * | 1979-06-15 | 1981-10-13 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| DE4402591A1 (de) * | 1993-01-29 | 1994-10-20 | Krka Tovarna Zdravil | Verfahren zur biotechnologischen Herstellung von Lovastatin und/oder Mevinolinsäure |
| WO1998037220A1 (en) * | 1997-02-20 | 1998-08-27 | Dsm N.V. | Nitrogen feed in statin fermentation |
-
2007
- 2007-02-09 ES ES200700519A patent/ES2319029B1/es active Active
- 2007-06-08 WO PCT/ES2007/000389 patent/WO2008096021A2/es active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4231938A (en) * | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| US4294926A (en) * | 1979-06-15 | 1981-10-13 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| DE4402591A1 (de) * | 1993-01-29 | 1994-10-20 | Krka Tovarna Zdravil | Verfahren zur biotechnologischen Herstellung von Lovastatin und/oder Mevinolinsäure |
| WO1998037220A1 (en) * | 1997-02-20 | 1998-08-27 | Dsm N.V. | Nitrogen feed in statin fermentation |
Non-Patent Citations (3)
| Title |
|---|
| CASAS LOPEZ J.L. ET AL.: "Lovastatin Inhibits its Own Synthesis in Aspergillus terreus", MICROBIOL. BIOTECHNOL., vol. 31, 2004, pages 48 - 50 * |
| RODRIGUEZ PORCEL E.M. ET AL.: "Effects of Pellet Morphology on Broth Rheology in Fermentations of Aspergillus terreus", BIOCHEM. ENGINEERING J., 2005, pages 139 - 144, XP005089018 * |
| RODRIGUEZ PORCEL E.M. ET AL.: "Enhanced Production of Lovastatin in a Bubble Column by Aspergillus terreus using a Two-Stage Feeding Strategy", J. CHEM. TECHNOL. BIOTECHNOL., vol. 82, January 2007 (2007-01-01), pages 58 - 64 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2319029B1 (es) | 2010-02-10 |
| ES2319029A1 (es) | 2009-05-01 |
| WO2008096021A2 (es) | 2008-08-14 |
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