The biocatalysis side of the group creates
genetically altered microbes to synthesize medicinal and
industrial chemicals from simple carbohydrates. This approach to
synthesis can facilitate replacement of an environmentally
problematic route to a given chemical with a route employing
renewable resources as feedstocks. Toxic starting materials,
toxic intermediates, and toxic byproducts can also be avoided.
Our conversion of glucose into adipic acid is one example of our
efforts to achieve environmentally compatible syntheses.
Microbial biocatalysts also provide access to natural products
capable of replacing chemicals currently synthesized via
environmentally problematic routes. For example, a microbe has
been created which synthesizes 3-dehydroshikimic acid (DHS), a
plant and fungal metabolite which is a more potent antioxidant in
various applications than butylated hydroxytoluene (BHT).
The bioorganic side of the group chemically synthesizes and
enzymologically evaluates selective inhibitors of
3-dehydroquinate (DHQ) synthase in microbes and S-adenosylhomocysteine (AdoHcy) hydrolase in mammals. These
enzymes are characterized by their catalytic use of nicotinamide
adenine dinucleotide (NAD) as an active site residue. Here the
goal is to exploit active site architecture to create molecules
which will be bound by the targeted enzymes in place of NAD.
Synthesized inhibitors are simultaneously being used as tools to
obtain insights into enzyme mechanism and as agents potentially
leading to medicinally important therapeutic activity.
Antibacterial and antifungal activities as well as antiviral and
anticancer activities are either precedented or predicted to
result from inhibition of the targeted enzymes.
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