Abstract
A method for obtaining maximum production of the bioproduct in fed-batch cultures is explained, and its validity is demonstrated by experimental data. The approach is based on a model which describes the relationship between the specific production rate, ϱ. and specific growth rate, μ. Using a mathematical model, an optimal profile of the specific growth rate could then be obtained easily by the Maximum Principle. Finally, the optimal profile was realized by changing the feed rate of the substrate in a practical fed-batch culture. Practical examples of bioproduction, such as histidine, lysine, and glutathione, as well as production of an enzyme, showed that the two-stage production process could be realized experimentally, thus demonstrating the validity of the method.
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Abbreviations
- a 1 :
-
model parameter in Eq. (7) (i=1, 2)
- b 1 :
-
model parameter in Eq. (7) (i=1, 2)
- E:
-
enzyme content of cells (U g−1)
- F:
-
feed rate of substrate (l h−1)
- F:
-
nominal feed rate of PF system (l h−1)
- ΔF :
-
feed rate for compensation of disturbance (l h−1)
- F NH3 :
-
ammonia feed rate per unit volume (mol l−1 h−1)
- H:
-
Hamiltonian
- L:
-
leucine concentration (g l−1)
- p:
-
product content of cells (mg g−1)
- P:
-
product concentration (histidine or lysine) (g l−1)
- S:
-
substrate concentration (g l−1)
- t:
-
time (h)
- t c :
-
switching time from μ max to μ c in the optimal profile (h)
- V:
-
working volume (l)
- X:
-
cell concentration (g l−1)
- Z:
-
cell mass (g)
- ϕ:
-
slope of H with respect to μ
- ψ:
-
defined in Eq. (10)
- λ i :
-
adjoint variable (i=1, 2)
- μ:
-
specific growth rate (h−1)
- ν:
-
specific consumption rate (h−1)
- ϱ:
-
specific production rate (h−1)
- 0:
-
at initial time
- C:
-
critical or switching
- E:
-
ethanol
- f:
-
at final time
- F:
-
feed
- G:
-
glutathione
- H:
-
histidine
- max:
-
maximum
- min:
-
minimum
- opt:
-
optimal
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© 1992 Springer-Verlag
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Shioya, S. (1992). Optimization and control in fed-batch bioreactors. In: Modern Biochemical Engineering. Advances in Biochemical Engineering/Biotechnology, vol 46. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0000708
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DOI: https://doi.org/10.1007/BFb0000708
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