John W. Frost
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.