Production of Pharmaceuticals

The overall vision of our research is to meet the need for critical plant-derived pharmaceuticals by using either whole plants or plant cell and tissue cultures as the production platform. The interest in plants and plant cell and tissue cultures for the production of natural products / specialized metabolites and biologics is increasing due to its scalability, lower costs, and lower infection risks to humans compared other cell culture systems.

In particular, we are investigating the production of important medicinal natural products from the Madagascar periwinkle (Catharanthus roseus) and the California poppy (Eschscholzia californica). 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 in plants or engineered cultures.

These two plant systems represent interesting models for exploring the bottlenecks to specialized 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 increasing production to the next level would require increasing the expression of several biosynthetic enzymes by engineering their transcriptional regulators. In the case of the California poppy, high levels of production can be achieved (i.e. 8% benzophenanthradine alkaloids 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 specialized metabolites from these two plant systems are the focus of our research. The intended outcome of our research is to develop synthetic biology and bioprocess strategies for enhancing production and thereby meeting the need for these critical plant-derived pharmaceuticals.

Below are 3 videos that highlight our findings and illustrate our approaches using tissue cultures, synthetic biology, and analytical chemistry:

1. Prof. Carolyn Lee-Parsons sharing two stories to illustrate our findings and our approaches
2. Ms. Amanda Dee, Bioengineering Major, on developing synthetic biology tools for engineering plant tissue cultures.
3. Ms. Charlotte Leggett and Mr. Joshua Garvey, Chemistry & Chemical Biology Majors, on identifying medicinal alkaloids produced in CRISPR-Cas9 edited cultures through mass spectrometry.

Many thanks for funding and support from the National Science Foundation, the MA Acorn Grant, the Mass Clean Energy Catalyst Grant, Northeastern Tier I and GapFund 360 Grants.