Terpenoids are compounds derived from isopentenyl pyrophosphate. They are the most numerous and structurally diverse group of natural products, with 22,000 members displaying more than 300 ring systems. Terpenoids that play crucial roles in vertebrates include the retinoids, the geranylgeranyl and farnesyl protein anchors, the coenzymes Q, vitamins A, D, and E, cholesterol, and the steroid hormones. Terpenoid hormones and pheromones are equally important in invertebrates. Plants control growth and development using regulatory terpenes including the gibberellins, the brassinosteroids, and abscissic acid. Many plants synthesize defense terpenoids that interfere with biological processes in potential herbivores. Some of these compounds are medicinally useful, such as taxol (anticancer), ginkgolide (which delays onset and progression of Alzheimer's disease), and artemisinin (antimalarial). We are cloning and characterizing genes encoding terpene cyclases and terpene oxidases, which catalyze terpene biosynthesis. We engineer microbial metabolic pathways by heterologously expressing these genes. The resultant strains produce natural products, many of which are difficult to obtain by existing methodology. Terpene synthases catalyze spectacular reactions, such as the conversion of epoxysqualene to cycloartenol. We are modifying terpene biosynthetic genes to produce catalysts that make novel natural products. In collaboration with Bonnie Bartel in this department, we are studying the function of terpenoids in the plant Arabidopsis thaliana.