Bioprocess Engineering
41
processes begin with a bioreactor. Despite
theadvancesinenzymetechno
logy
,i
tis
important to keep in mind that enzymes
come from cells; thus, whole-cell biore-
actor technology will be important for
enzyme production as well as for produc-
tion of vaccines, insecticides, antibodies,
hormones, immunobiological regulators,
and artiFcial tissue.
The roots of fermentation technology are
traced back to many centuries. The earliest
bioreactors or fermentors were used in the
brewing and wine-making industries. Dur-
ing the last 50 years, fungal fermentations
have been used to make antibiotics, begin-
ning with penicillin. Recombinant DNA
technology, monoclonal antibody produc-
tion, and genomic research continue to
push the whole-cell reactor technology
forward. The Frst major products made
by recombinant organisms were insulin
(Eli Lilly), tissue plasminogen activator
(Genetech), and erythropoietin (Amgen).
Today the major question that remains
is how to choose the best host–vector
system. The most common hosts for com-
mercial production are the bacterial strain,
Escherichia coli
, and the Chinese hamster
ovary (CHO) cells. A comparison of the ad-
vantages and disadvantages of using these
two types of cell systems is given in Table 1.
Overall, the choice of the host–vector sys-
tem is very complicated and the ‘‘ideal’’
system does not as yet exist. The character-
istics of the protein product and cost are
the critical values. ±or example, if a bulk
enzyme for detergents is being produced,
some impurities are okay, and bacterial
Tab. 1
Comparison of bacterial and mammalian cell host–vector systems for product synthesis.
E. coli cultures
CHO cell cultures
Advantages
Disadvantages
Advantages
Disadvantages
High growth rate
Formation of inclusion
bodies
Availability of host and
vector systems
Slow growth
Wide range of host
backgrounds
Misfolded protein
products
Excretion of product
Expensive, complex
media
Wide range of vectors
and promoters
No ability to glycosylate
Ability to produce
authentic proteins
(correct folding,
glycosylation, and
posttranslational
processing)
Low protein expression
levels
High expression levels
and cell densities
Proteolytic activity
Low proteolytic activity
Shear sensitive cells
Low-cost media
Usually low levels of
product excretion
Vectors are derived
from virus and there
is fear of reversion to
pathogenic form.
No posttranslational
processing
Must assure removal of
nucleic acids from
hybridoma lines
Must assure removal of
endotoxins during
puri±cation
Most strains are mortal
so dead cells must
be removed.
previous page 715 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 717 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off