Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

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.