Justin Miller

Cytochrome P450 enzymes are best known for their oxidation chemistries that metabolize drugs in the human body. Less well known are those in other organisms (e.g., plants) that employ P450s to modify any number of natural products used as defense compounds against insect predation and/or microbial infection. Many of these natural products are the source of pharmaceutical skeletons that allow humans to benefit from some very exotic plant P450 chemistry. Key among these are derivatives of the terpene indole alkaloid (TIA) pathway whose early products (leading to strictosidine) are synthesized in at least 80 medicinal plants and whose later products (leading to species-specific products) are utilized in cancer and viral treatments. Working in this pathway that includes at least five P450s, I am designing enzymes that transfer their particular regio- and stereo-selectivities to a wider array of substrates with the goal of developing novel natural product-like compounds.