This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Catharanthus roseus plant is the source of the important antitumor compounds, vincristine and vinblastine, used in the treatment of leukemia, Hodgkin's disease, and certain lymphomas, and the antihypertensive compounds, ajmalicine and serpentine. The plant contains extremely low concentrations of these alkaloid compounds (0.0005%-0.3% by weight), resulting in their high prices. Moreover, production of these compounds from the plant is inconsistent, being sensitive to changes in the environment. In order to overcome these limitations, Prof. Lee is investigating how the various production-enhancing strategies alter the flux of nutrients, precursors, and resources in the primary and secondary metabolic pathways. Her goal is to develop an economically viable process using plant cell culture to meet the needs and demands of important plant-derived pharmaceuticals. The research approach is to investigate the underlying mechanism by which secondary metabolite production is increased inside the cell and to rationally manipulate the external conditions to cause desirable changes inside the cell. Some compounds known to be in the biochemical pathway could be identified in the fractions, on the basis of their molecular weights and reported tandem MS, or comparison of the spectra obtained for the submitted samples with those of standards. The complementary collaborative project explores fragmentation pathways of the alkaloids on the qTOF and FTMS instruments.
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