Continuous Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 621

Under normal circumstances S 0 >> K S , so the rate of chemostat biomass production, P XC ,is

approximately

P XC ¼ðDXÞ opt z ðm max k d ÞYF X = S S 0 (12.29)

P XC

P XB ¼ ln X X 0 þ t P ðm max k d Þ

(12.30)

Most commercial fermentations operate with X/ X 0 ¼ 10 e 20. Thus, we would expect contin-

uous systems to always have a significant productivity advantage for primary products. For
example, an Escherichia coli fermentation with X/ X 0 ¼ 20, t P ¼ 5 h, and m max k d ¼ 1.0/h

would yield P XC / P XB ¼ k d .

Figure 12.8 shows a comparison of (a) batch and (b) continuous cultivations of Saccharo-
myces cerevisiae LBG H 1022 (ATCC 3216) in 4 m 3 air-lift reactor with a glucose-limited
medium. There are noticeable differences in the growth and by-product (ethanol) formation
between the two cultivation techniques. For batch cultivation ( Fig. 12.8 a), there is a notice-
able lag phase observed (for the first 5 e 8 h). Both ethanol concentration and cell biomass
concentration increase as glucose is consumed after the lag phase and until 16 h. After
glucose is completely consumed, the cells turned to ethanol as the substrate, leading to
the decrease in ethanol concentration and further increase in the cell biomass concentration.
There is a noticeable diauxic phase between the batch cultivation time of 16 and 19 h. The
secondary growth is pronounced after 19 h. For the continuous cultivation ( Fig. 12.8 b),
the cell biomass concentration is at maximum when the dilution rate is low (D

8 as in the maximum growth regime, m net ¼ m max

< 0.17/h)

D 1 or at long residence times ( 5.9 h). Almost all the glucose is consumed in the

reactor and there is no ethanol produced. When the dilution rate is increased beyond
0.17 h 1 , glucose concentration increases in the reactor. The Crabtree effect is observed
and a sudden increase in the ethanol concentration in the reactor. The cell biomass concen-
tration decreases as the dilution rate is increased. When the dilution rate is increased
beyond the maximum growth rate of the yeast cells, the glucose concentration rise to its
initial feed value and the cells are washed out. The productivity of the continuous cultiva-
tion is significantly higher than that of the batch cultivation. The maximum cell dry mass
concentration is reached after 26 h of batch cultivation, whereas the residence time in the
continuous cultivation is 5.9 h.
Based on this productivity advantage, we might be surprised to learn that most commer-
cial bioprocesses are batch systems. Why? There are several answers. The first is that Eqn
(12.30) applies only to growth-associated products. Many secondary products are not
made by growing cells; growth represses product formation. Secondary metabolites are
produced when cells are under stress and lacking one or more nutrients. Under such circum-
stances, product is made only at very low dilution rates, far below those values optimal for
biomass formation. For secondary products, the productivity in a batch reactor may signifi-
cantly exceed that in a simple single chemostat. Another primary reason for the choice of
batch systems over chemostats is genetic instability . The biocatalyst in most bioprocesses
has undergone extensive selection. These highly “bred” organisms often grow less well
than the parental strain. A chemostat imposes strong selection pressure for the most rapidly
growing cell. Back mutation from the productive specialized strain to one similar to the less
productive parental strain (i.e. a revertant) is always present. In the chemostat, the less

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