The overall vision of our research is to meet the need for critical plant-derived pharmaceuticals by using plant cell cultures as the method of production. The interest in plant cell cultures as a production platform for natural products and biologics is increasing due to its lower costs and lower infection risks compared other cell culture systems.
In particular, we are investigating the production of important medicinal natural products from cultures of the Madagascar periwinkle (Catharanthus roseus, Figure 1) and the California poppy (Eschscholzia californica, Figure 2). The Madagascar periwinkle produces vincristine and vinblastine used in the treatment of cancers. The high cost of these critical anti-cancer compounds ($4 – $20 million/kg, Source: Thomson Reuters’ Red Book) motivates our research to better understand their biosynthesis and ultimately overproduce them economically using cultures derived from the Madagascar periwinkle.
Cultures from these two plant systems represent interesting models for exploring the bottlenecks to secondary metabolite production and for elucidating the fundamental regulatory and metabolic mechanisms leading to increased production. In the case of the Madagascar periwinkle, the production of its compounds from tissue cultures appears to be limited at the transcriptional level. Gene expression studies indicate that a specific enzyme is likely to be limiting but that increasing production to the next level would require increasing the expression of several enzymes involved in its biosynthesis. In the case of the California poppy, significantly high levels of production can be achieved (i.e. 8% by dry weight) and global proteomics was applied to explore the potential regulatory or metabolic mechanisms that support this enhanced production. The complex regulation and the bottlenecks to the production of secondary metabolites from these two plant culture systems are the focus of our research. The intended outcome of our research is to develop biochemical and genetic engineering strategies for overcoming these limitations.
Funded by the National Science Foundation.