Sources and upstream processing - Pharmaceutical Biotechnology: Concepts and Aapplications - page 108

Table 5.1 Expression systems which are/could potentially be used
for the production of recombinant biopharmaceutical products

E. coli (and additional prokaryotic systems, e.g. bacilli)
Yeast (particularly S. cerevisiae )
Fungi (particularly aspergilli)
Animal cell culture (particularly CHO and BHK cell lines)
Transgenic animals (focus thus far is upon sheep and goats)
Plant-based expression systems (various)
Insect cell culture systems

methods of fermentation. Production facilities can be constructed in any world region, and the
scale of production can be varied as required.
The expression of recombinant proteins in cells in which they do not naturally occur is termed
heterologous protein production (Chapter 3). The fi rst biopharmaceutical produced by genetic
engineering to gain marketing approval (in 1982) was recombinant human insulin (tradename
'Humulin'), produced in E. coli. An example of a more recently approved biopharmaceutical that
is produced in E. coli is that of Kepivance, a recombinant keratinocyte growth factor used to treat
oral mucositis (Chapter 10). Many additional examples are provided in subsequent chapters.
As a recombinant production system, E. coli displays a number of advantages. These include:

• E. coli has long served as the model system for studies relating to prokaryotic genetics. Its mo-

lecular biology is thus well characterized.

• High levels of expression of heterologous proteins can be achieved in recombinant E. coli

(Table 5.3). Modern, high-expression promoters can routinely ensure that levels of expression
of the recombinant protein reach up to 30 per cent total cellular protein.

• E. coli cells grow rapidly on relatively simple and inexpensive media, and the appropriate

fermentation technology is well established.

These advantages, particularly its ease of genetic manipulation, rendered E. coli the primary
biopharmaceutical production system for many years. However, E. coli also displays a number of
drawbacks as a biopharmaceutical producer. These include:

Table 5.2 Some biopharmaceuticals currently on the market which
are produced by genetic engineering in either E. coli or animal cells

Biopharmaceutical Source Biopharmaceutical Source

tPA E. coli , CHO FSH CHO

Insulin E. coli IFN-β CHO

EPO CHO

IFN-α E. coli Glucocerebrosidase CHO

IFN- γ E. coli Factor VIIa BHK

IL-2 E. coli

G-CSF E. coli

hGH E. coli