|This article does not cite any references or sources. (December 2007)|
A fed-batch is a biotechnological batch process which is based on feeding of a growth limiting nutrient substrate to a culture. The fed-batch strategy is typically used in bio-industrial processes to reach a high cell density in the bioreactor. Mostly the feed solution is highly concentrated to avoid dilution of the bioreactor. The controlled addition of the nutrient directly affects the growth rate of the culture and helps to avoid overflow metabolism (formation of side metabolites, such as acetate for Escherichia coli, lactic acid in cell cultures, ethanol in Saccharomyces cerevisiae), oxygen limitation (anaerobiosis).
Substrate limitation offers the possibility to control the reaction rates to avoid technological limitations connected to the cooling of the reactor and oxygen transfer. Substrate limitation also allows the metabolic control, to avoid osmotic effects, catabolite repression and overflow metabolism of side products.
Different strategies can be used to control the growth in a fed-batch process:
|Control Parameter||Control Principle|
|DOT (pO2)||DOstat (DOT= constant), F~DOT|
|Oxygen uptake rate (OUR)||OUR=constant, F~OUR|
|Glucose||on-line measurement of glucose (FIA), glucose=constant|
|Acetate||on-line measurement of acetate (FIA), acetate=constant|
|pH (pHstat)||F~pH (acidification is connected to high glucose)|
|Ammonia||on-line measurement of ammonia (FIA), ammonia=constant|
|Temperature||T adapted according to OUR or pO2|
- Hewitt CJ, Nienow AW: The scale-up of microbial batch and fed-batch fermentation processes. Adv Appl Microbiol 2007, 62:105-135.
- Wlaschin KF, Hu WS: Fedbatch culture and dynamic nutrient feeding. Cell Culture Engineering 2006, 101:43-74.
- Shiloach J, Fass R: Growing E. coli to high cell density--a historical perspective on method development. Biotechnol Adv 2005, 23:345-357.
- Panda AK: Bioprocessing of therapeutic proteins from the inclusion bodies of Escherichia coli. Adv Biochem Eng Biotechnol 2003, 85:43-93.
- Liden G: Understanding the bioreactor. Bioprocess and Biosystems Engineering 2002, 24:273-279.
- Neubauer P, Winter J: Expression and fermentation strategies for recombinant protein production in Escherichia coli. In: Merten OW et al. (Eds). Recombinant Protein Production with prokaryotic and eukaryotic cells. A comparative view on host physiology. 2001, Kluwer Academic Publisher, Dordrecht, The Netherlands. pp. 196-260.
- Balbas P: Understanding the art of producing protein and nonprotein molecules in Escherichia coli. Molecular Biotechnology 2001, 19:251-267.
- Lee J, Lee SY, Park S, Middelberg AP: Control of fed-batch fermentations. Biotechnol Adv 1999, 17:29-48.
- Zhang J, Greasham R: Chemically defined media for commercial fermentations. Applied Microbiology and Biotechnology 1999, 51:407-421.
- Lee SY: High cell-density culture of Escherichia coli. Trends Biotechnol 1996, 14:98-105.
- Mendozavega O, Sabatie J, Brown SW: Industrial-Production of Heterologous Proteins by Fed-Batch Cultures of the Yeast Saccharomyces-Cerevisiae. Fems Microbiology Reviews 1994, 15:369-410.
- Yee L, Blanch HW: Recombinant protein expression in high cell density fed-batch cultures of Escherichia coli. Biotechnology (N Y ) 1992, 10:1550-1556.
- Riesenberg D, Schulz V: High-cell-density cultivation of Escherichia coli. Curr Opin Biotechnol 1991, 2:380-384.