Fed-Batch Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 691

metabolism of side products. Therefore, there are different operation strategies for fed-batch:
1) constant feed rate or constant growth/fermentation rate; 2) exponential feed rate or constant
specific growth rate. The exponential growthwith fed-batch operation can be at any rate, up to
the maximum rate in the exponential growth phase of a batch growth. This is the case that
closely resembles a chemostat operation. Usually, maximum growth rate is not wanted
because the undesired by-product production can be high at maximum growth.
Analysis of fed-batch reactors is more complex than either chemostat or batch reactor.
Solutions of differential equations are usually required. When long operation time is
employed, a pseudo-steady state may be assumed and thus simplifying the analysis. The
pseudo-steady state is found to correspond to biomass steady state or d d t ¼ 0

. Some solu-
tions for the biomass concentration and product formation are shown in Table 13.1 for
constant feed and exponential feed at pseudo-steady state conditions.

Further Reading

Curless, C., Fu, K., Swank, R., Menjares, A., Fieschko, J., Tsai, L., 1991. Design and Evaluation of a 2-Stage, Cyclic,
Recombinant Fermentation Process, Biotechn. Bioeng . 38 (9) 1082 1090.

Hewitt, C.J., Nienow, A.W., 2007. The scale-up of microbial batch and fed-batch fermentation processes. Adv. Appl.
Microbiol . 62, 105

e

135.
Wlaschin, K.F., Hu, W.S., 2006. Fedbatch culture and dynamic nutrient feeding. Cell Culture Engineering 101, 43

e

74.
Shiloach, J., Fass, R., 2005. Growing E. coli to high cell density-a historical perspective on method development.
Biotechnol. Adv . 23, 345

e

357.
Liden, G., 2002. Understanding the bioreactor. Bioprocess and Biosystems Engineering 24, 273

e

279.
Lee, J., Lee, S.Y., Park, S., Middelberg, A.P., 1999. Control of fed-batch fermentations. Biotechnol. Adv . 17, 29

e

48.

e

Lee, S.Y., 1996. High cell-density culture of Escherichia coli . Trends Biotechnol 14, 98 105.

Mendozavega, O., Sabatie, J., Brown, S.W., 1994. Industrial-Production of Heterologous Proteins by Fed-Batch
Cultures of the Yeast Saccharomyces-Cerevisiae . Fems Microbiology Reviews 15, 369

e

410.
Yee, L., Blanch, H.W., 1992. Recombinant protein expression in high cell density fed-batch cultures of Escherichia coli .
Biotechnology (NY) 10, 1550

e

1556.
Riesenberg, D, Schulz, V., 1991. High-cell-density cultivation of Escherichia coli . Curr. Opin. Biotechnol . 2, 380

e

384.

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PROBLEMS

13.1. Penicillin is produced by P. chrysogenum in a fed-batch culture with the intermittent
addition of glucose solution to the culture medium. The initial culture volume is
V 0 ¼

200 L, and glucose-containing nutrient solution is added with a flow rate of

Q 30 L/h. Glucose concentration in the feed solution and the initial concentrations in

the reactor are S F ¼

¼

300 g/L, S 0 ¼ 1 g/L, and X 0 ¼ 20 g/L. The kinetic and yield factors

0.2 h 1 , K S ¼ of the organism are 0.3 g-dw/g-glucose.

Without invoking the pseudo-steady state approximation, determine and compare with
Example 13-1:
(a) the culture volume at t

m max ¼ 0.5 g/L, and YF X/S ¼

24 h;
(b) the concentration of glucose at t

¼

¼ 24 h;