Biomedical Engineering Reference
In-Depth Information
Glucose
Glyceraldehyde
3-phosphate
Lycopene
Pyruvate
NR
I
Acetyl
phosphate
NR
I
-P
Acetate
Expression
NR
I
-P
binding
region
glnAp2
promoter
lac
Z or lycopene biosynthesis
genes
Fig. 14.20
Construction of a metabolic
control circuit. See text for details.
(lycopene) formation was controlled by the meta-
bolic state of the cell. Although metabolic control
engineering is still at an early stage, it represents a
significant degree of sophistication of control com-
pared with the use of simple controllable promoters.
metabolic pathways of plants are so extensive and
complex that, in most cases, such a strategy would
prove impossible. Fortunately, advances in plant
transformation have made it possible to carry out
metabolic engineering in plants themselves, and
large-scale plant cell cultures can be used in the
same manner as microbial cultures for the produc-
tion of important phytochemicals (reviewed by
Verpoorte 1998, Verpoorte
et al.
2000).
The secondary metabolic pathways of most plants
produce the same basic molecular skeletons, but
these are 'decorated' with functional groups in a
highly specific way, so that particular compounds
may be found in only one or a few plant species.
Furthermore, such molecules are often produced in
extremely low amounts, so extraction and purification
can be expensive. For example, the Madagascar
periwinkle
Catharanthus roseus
is the source of two
potent anti-cancer drugs called vinblastine and
vincristine. These terpene indole alkaloids are too
complex to synthesize in the laboratory and there
are no alternative natural sources. In
C. roseus
, these
molecules are produced in such low amounts that
over 1 ha of plants must be harvested to produce a
single gram of each drug, with a commercial value of
over $1 million.
It would be much more convenient to produce
such drugs in fermenters containing cultured plant
cells, and this has been achieved for a number of
Metabolic engineering in plant cells
Plants synthesize an incredibly diverse array of
useful chemicals. Most are products of
secondary
metabolism
- that is, biochemical pathways that are
not involved in the synthesis of essential cellular
components but which synthesize more complex
molecules that provide additional functions. Examples
of these functions are attraction of pollinators and
resistance to pests and pathogens. In many cases,
these secondary metabolites have specific and potent
pharmacological properties in humans: well-known
examples include caffeine, nicotine, morphine and
cocaine.
Plants have long been exploited as a source of
pharmaceutical compounds, and a number of species
are cultivated specifically for the purpose of extract-
ing drugs and other valuable molecules. We dis-
cussed above how gene transfer to bacteria and
yeast can be used to produce novel chemicals, so in
theory it would be possible to transfer the necessary
components from these useful plants into microbes
for large-scale production. However, the secondary
