EAGER: Unveiling the transport mechanism of biosynthetic curcumin in engineered Escherichia coli

Plants are the original source for many of the drug compounds we now use. These compounds are often only slightly soluble in water (hydrophobic). This works fine once inside the human body, because our cell membranes are also hydrophobic. It is a problem when developing large-scale processes for biomanufacturing of these processes. Cells are grown in water-based environments. Hydrophobic compounds will tend to stay in the cells, making separation and purification difficult. The project will investigate a new strategy for producing these compounds. They will be modified inside the cell to make them water-soluble. This will allow them to achieve high concentrations in the growth medium. The focus of this project will be on characterizing how these molecules are transported out of the cell. The long-term goal of this project is to develop a novel strategy for producing hydrophobic biomolecules by synthesizing them inside the cell as water-soluble conjugates and then hydrolyzing them to final form after they are excreted from the cell into the aqueous medium. This would take advantage of the large concentration gradient across the cell membrane as a driving force for transport of the molecule into the medium. The immediate goal of this project is to characterize the mechanisms controlling the transport of the model compound, curcumin, in E. coli with a specific focus on the surface binding mechanisms involved in the process. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.