study biochemical engineering in Tan Hall. Some of our many projects
include the development of new enzyme technology, the analysis of extremophilic
microorganisms that have adapted to harsh living environments, and the
study of cancer cell metabolism.
our groups recent research involves the development of new enzyme
systems that have practical applications, from drug discovery to large-scale
bioprocesses in industry. Enzymes are complex proteins produced by living
cells that catalyze specific biochemical reactions under physiological
conditions. Scientists have studied enzymes in test tubes for decades
and have worked out many of their catalytic mechanisms. However, enzymes
are not widely used in the chemical and pharmaceutical industries because
once out of the cell, many enzymes lose their activity and stability.
We have devised ways to greatly increase the activity and stability
of enzymes under conditions suitable for the synthesis of chemicals
and pharmaceuticals, namely under high pressure and temperature, and/or
in organic solvents. These developments are particularly important for
the large-scale application of enzymes in pharmaceutical, chemical,
and agrochemical industries.
For example, we and coworkers pioneered combinatorial biocatalysis,
a technique that uses enzymes and microbes to derive small-molecule
lead compounds from a common starting compound. Combinatorial biocatalysis
is an emerging technology in the field of drug discovery. The biocatalytic
approach to combinatorial chemistry uses enzymatic and microbial transformations
to generate libraries from lead compounds. Those derivative libraries
can then be screened against various bacteria and diseases to look for
a desired activity. This technology has had an immediate impact on the
use of biocatalysis in drug discovery. Through research performed in
Tan Hall and at several biotechnology and pharmaceutical companies,
combinatorial biocatalysis has been used to generate many new drug candidates
for clinical investigation, including new analogs of the anticancer
drugs taxol and doxorubicin. Current biocatalysis projects involve the
generation of new anti-cholesterol agents using unique compounds produced
by a deep-sea organism as a starting point, and the biocatalytic synthesis
of new anti-HIV compounds.
We are also trying to find ways to practically exploit microorganisms
that have been isolated from extreme environments, such as hydrothermal
vents that lie deep in the ocean. These versatile extremophiles
are able to grow and survive in harsh environments and could therefore
be adapted to catalyze reactions in the broad range of process conditions
that are used in industry. For this research, our group has built specialized
equipment that can duplicate the most extreme conditions on Earth that
are known to support life, i.e., high temperatures and greatly elevated
pressures. By studying extremophiles under these conditions, we have
been able to examine mechanisms by which these robust organisms adapt
to stressful extremes, and to explore new bioprocesses at the outer
limits of life.
Another major activity within the group, in collaboration with Professor
Blanch, concerns the monitoring and modeling of complex metabolic
reaction networks in breast cancer cells. This research involves the
use of a relatively new technique, metabolic flux analysis, to study
the major metabolic pathways, and complex interactions
among them, in cancer cells under different growth conditions and treatment
regimens. This approach therefore enables comprehensive examination
of cancer-cell metabolism and may reveal drug targets for new therapies
to control cancer cell proliferation.
A high temperature-pressure bioreactor in Tan Hall designed to mimic
extreme environments that can support life. The inset at the top left
shows an extremophile isolated from a deep-sea hydrothermal vent.