A fed-batch culture operation is characterized by predetermined or controlled addition of nutrient medium in an otherwise batch operation (no withdrawal of culture). This operation allows for temporal variation in the supply of nutrients, thereby allowing tighter control of various cellular processes such as cell growth, nutrient uptake and production of target metabolites. As mentioned earlier, synthesis of secondary metabolites, including a variety of antibiotics and enzymes, is promoted under culture conditions where cell growth is discouraged. Controlled addition of nutrients in a fed-batch operation allows for control of cell growth and thereby promotes production of secondary metabolites. The total mass of culture increases during a fed-batch operation and so does the culture volume unless nutrients in highly concentrated form (such as solid powders) are fed to the culture. The feed rate can be varied in a predetermined fashion or by using feedback control. The addition of nutrient feed is terminated upon reaching the maximum permissible volume. A fed-batch operation may be followed by a terminal batch operation, with culture volume being equal to maximum permissible volume, to utilize the nutrients remaining in the culture at the end of fed-batch operation. A fed-batch operation is usually preceded by a batch operation. A typical run involving fed-batch operation therefore very often consists of the fed-batch operation sandwiched between two batch operations. This entire sequence (batch—vfed-batch—»batch) may be repeated many times leading to serial (or repeated) fed-batch operation. As in the case of repeated batch operation with recycle, transfer of culture from one sequence to the next to inoculate the next sequence is common in these serial operations.
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