Designing microbes to build drugs
By harnessing the molecular factories inside of well-understood
bacteria such as E. coli, we can synthesize drugs quickly, cheaply,
and environmentally responsibly. These methods can provide vast
societal benefits for developing countries.
Many important compounds are produced naturally in plants or microorganisms
in very minute quantities and need to be extracted and concentrated before
use, a process that is environmentally unfavorable. We have demonstrated
the ability to re-engineer the cellular apparatus of microbes to produce
amplified amounts of these useful compounds. In addition, we are able
to engineer these microorganisms to produce derivatives of these molecules
that are not found in nature but may be more effective in treating human
ailments.
Case
study: arteminisin
Arteminisin is a promising next-generation anti-malarial drug that is
badly needed in African and South American countries where the disease
is becoming resistant to cheaper front-line medications. But the cost
of extracting, purifying and concentrating the active ingredient from
the wormwood plant (left) is often prohibitive. We've reconstituted
a metabolic pathway from yeast in E. coli, synthesized the drug
precursor gene from wormwood, then optimized the pathway for 10,000-fold
increase in productivity, to perform simply and cheaply many of the chemical
steps needed to synthesize the drug.
