Grant: Discovery Grants Program - Individual

Plants have remarkable attributes for being able to perform complex and biologically innovative biochemistry that generates a diversity of colors, fragrances, aromas and biologically active organic molecules. While the majority of the molecules produced are not directly essential for survival, many may play key roles in plant adaptation to the biotic and abiotic environment. The unique biological activities of this chemical diversity have provided medicinal and disease preventing molecules that have been used by humanity to prevent/cure many devastating diseases. The monoterpenoid indole alkaloids (MIAs) make up the largest and most diverse class of compounds that are characteristically found within many members of the Apocynaceae (4700 species), the Loganiaceae (600 species) and the Rubiaceae (> 10,000 species) plant families. The complexity of MIA chemistry is matched by their remarkably diverse effects on living organisms that has led to their use as drugs for preventing malaria (quinine) and for treating neurological disorders (reserpine), cancer (camptothecin, vinblastine and vincristine), as vasodilators (yohimbine), as anti-inflammatories for gout treatments (colchicine) and as potential analgesics and novel pain killers (conolidine) in human beings. Over the past >25 years my laboratory has made many key discoveries about the biosynthesis of anti-cancer MIAs of the Madagascar periwinkle (Catharanthus roseus) that have been used in chemotherapy treatments over the past 45 years. The genetic resources and biochemical knowledge derived from these discoveries are presently being exploited to enhance the production of valuable medicinal compounds in C. roseus or through synthetic biology experiments in other organisms including yeast or in microbial factories. The production of MIA pharmaceuticals in recombinant organisms creates unique opportunities for less expensive manufacturing of existing MIA drugs and for generating new and unique medicines not available from natural sources. The initial discoveries made in this model plant have also greatly improved the tools available for gene discovery of other MIA pathways found in Nature and for learning about the ecological roles that MIAs play in plant fitness and adaptations to their environment.