Plant secondary metabolites are an important source of therapeutic drugs or drug leads. The advent of genomic and metabolomic technologies has now made it possible to bring the field of plant natural products into the 21st century and replace serendipitous and haphazard finding by rational design and discovery. This proposal is devoted to plant terpenes, the largest and most diverse group of plant natural products. TERPMED will focus on sesquiterpene lactones and phenolic diterpenes because of the presence of distinct functional groups and their high potential as novel human drugs for treating cancer and neurological disorders. By using a combination of comparative metabolomics and genomics, significant advances will be achieved in the understanding of the biosynthetic pathways of these compounds. Focusing on specific functional groups such as γ-butyrolactones and phenolics amongst the terpenes will allow the development of high-throughput analytical methodologies to detect, purify and characterize compounds bearing these groups. A comprehensive library of these compounds within a subset of plant biodiversity will be established. The compounds isolated will be tested for biological activity and the most active molecules will be selected. High throughput cDNA sequencing coupled to the comparative analysis of the metabolic profiles of targeted species will be achieved for the elucidation of the biosynthetic pathways of these compounds. Innovative production platforms using plant secretory organs such as the trichomes will be tested for the pilot production of the most promising compounds identified and the production of novel compounds by combinatorial biosynthesis.