Abstract |
Biotechnology is often presented as if progress in the past two decades represented a major success, but the reality is quite different. For example, ten major classes of antibiotics were discovered between 1935 and 1963, but after 1963 there has been just one, the oxazolidones. To illustrate the possibilities of doing better by taking account of the real behaviour of metabolic systems, we can examine how one might modify the activity of an enzyme in the cell (for example by genetic manipulation, or by the action of an inhibitor, etc.) to satisfy a technological aim. For
example, if the objective is to eliminate a pest, one might suppose
that the effect of an inhibitor could be to depress an essential
flux to a level insufficient for life, or to raise the concentration
of an intermediate to a toxic level. The former may seem the more
obvious, but the latter is easier to achieve in practice, and there
are some excellent examples of industrial products that work in
that way, such as the herbicide Roundup and antimalarials of the
quinine class. A study of glycolysis in the parasite Trypanosoma
brucei (the cause of African sleeping sickness) indicates that
for this approach to work the selected target enzyme must have
a substrate with a concentration that is not limited by stoicheiometric
constraints. That is not necessarily easy to find in a complicated
system, and typically needs the metabolic network to be analysed
in the computer. |