Claims
- 1. A fermentation process wherein a microorganism ferments a fermentation substrate and specific oxygen uptake rate is monitored during a production phase of the fermentation process, and at least one operating parameter is controlled in response to the measured oxygen uptake rate.
- 2. The process of claim 1, wherein the dissolved oxygen concentration is maintained at less than 1% of the saturation amount.
- 3. The process of claim 2, wherein the operating parameter is one or more selected from the group consisting of aeration rate, agitation rate, and aeration gas composition.
- 4. The process of claim 2, wherein the microorganism is a genetically engineered yeast having a disruption of a native PDC pathway.
- 5. The process of claim 4, wherein the microorganism has at least one functional exogenous gene that enables the cell to produce a desired fermentation product.
- 6. The process of claim 5, wherein the exogenous gene is a lactate dehydrogenase gene.
- 7. The process of claim 6, wherein the microorganism is of the genera Candida or Kluyveromyces.
- 8. A method of conducting a fermentation process in a fermentation medium comprising a fermenting microorganism, a substrate that is fermentable by the microorganism, wherein the fermentation broth has a quantity of dissolved oxygen (DO) and the fermentation exhibits a specific oxygen uptake (OUR), comprising
a) measuring the OUR during a production phase of a fermentation; b) adjusting aeration conditions such that the OUR is maintained within a predetermined range while maintaining the DO below 1% of saturation during the production phase of the fermentation.
- 9. The process of claim 8, wherein the OUR in step b) is maintained in a range from about 0.8 to about 3.0 mmol O2/gdw/h, and the DO is maintained below 10 mmol O2/L.
- 10. The process of claim 9, wherein the microorganism is a yeast cell exhibiting a Crabtree negative phenotype.
- 11. The process of claim 10, wherein the yeast cell is of the genera Kluyveromyces or Candida.
- 12. The process of claim 11, wherein the yeast cell has a disrupted PDC pathway and at least one functional exogenous gene that enables the cell to produce a desired fermentation product.
- 13. The process of claim 12, wherein the exogenous gene is a lactate dehydrogenase gene.
- 14. The process of claim 8, wherein the substrate includes a hexose sugar.
- 15. The process of claim 14, wherein the hexose sugar includes glucose.
- 16. A process comprising
a) determining an optimum range of OUR values at which a microorganism ferments a carbohydrate to a desired fermentation product; b) growing the engineered yeast cell in a medium comprising a carbohydrate that the microorganism is capable of metabolizing and one or more nutrients, while aerating the medium such that the cells as the cells grow and reproduce, the concentration of dissolved oxygen in the medium is reduced to less than 1% of saturation and the cells exhibit a specific oxygen uptake rate of at least 10 mmol O2/g dry weight of cells/hour (mmol O2/gdw/h); and then c) culturing the cells in a buffered medium under fermentation conditions including microaeration conditions sufficient to provide the culture with a specific oxygen uptake rate (OUR) within the optimum range.
- 17. The process of claim 9, wherein the microorganism is a yeast cell is exhibiting a Crabtree negative phenotype.
- 18. The process of claim 17, wherein the yeast cell is of the genera Kluyveromyces or Candida.
- 19. The process of claim 18, wherein the yeast cell has a disrupted PDC pathway and at least one functional exogenous gene that enables the cell to produce a desired fermentation product.
- 20. The process of claim 19, wherein the exogenous gene is a lactate dehydrogenase gene.
- 21. The process of claim 16, wherein the OUR in step a) is at least 18 mmol O2/gdw/h.
- 22. The process of claim 21, wherein the carbohydrate includes a hexose sugar.
- 23. The process of claim 22, wherein the hexose sugar includes glucose.
- 24. A fermentation process comprising
a) growing engineered yeast cells having a disrupted PDC pathway and an exogenous gene which allows the cell to produce a desired fermentation product, in a medium comprising a carbohydrate that the cell is capable of metabolizing, while aerating the medium such that the cells as the cells grow and reproduce the dissolved oxygen tension in the medium is reduced to zero and the cells exhibit a specific oxygen uptake rate of at least 10 mmol O2/g dry weight of cells/hour (mmol O2/gdw/h); and then b) culturing the cells in a buffered medium under fermentation conditions including microaeration conditions sufficient to provide the culture with a specific oxygen uptake rate (OUR) of about 0.8 to about 3.0 mmol O2/gdw/h.
- 25. The process of claim 24, wherein the yeast cell is of a Crabtree negative phenotype
- 26. The process of claim 25, wherein the exogenous gene is a lactate dehydrogenase (LDH) gene.
- 27. The process of claim 26, wherein the yeast cell is of the genera Kluyveromyces or Candida.
- 28. The process of claim 24, wherein the OUR in step a) is at least 18 mmol O2/gdw/h.
- 29. The process of claim 24, wherein the carbohydrate includes a hexose sugar.
- 30. The process of claim 28, wherein the hexose sugar includes glucose.
BACKGROUND OF THE INVENTION
[0001] This application claims priority to U.S. Provisional application No. 60/384,333, filed May 30, 2002.
Government Interests
[0002] This invention was made with U.S. Government support under Contract No. DE-FC-36-00GO10598, awarded by the Department of Energy. The U.S. government has certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60384333 |
May 2002 |
US |