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The Characterization of Uridine 5'-diphosphoglycosyltransferases (UGT's) in Foxglove for Digitoxin Biosynthesis
Abstract
Digitalis lanata, more commonly known as the Grecian Foxglove, is a plant species that produces secondary metabolites referred to as cardiac glycosides. Cardiac glycosides are produced as a plant defense mechanism against predation. In Digitalis, the two most utilized cardiac glycosides are Digoxin and Digitoxin. These compounds have been used by people for centuries in the treatment of a variety of heart conditions. Current methods of production for these two compounds involve harvesting the leaves of the D. lanata plant and isolating the compounds. This process is not the most ideal option as extracting the drugs from the plant is time consuming and inefficient. Identifying the key enzymes in the biosynthetic pathway of Digoxin and Digitoxin offers a new approach to producing the drugs, as this pathway can then be replicated in a microbial Setting. This study in particular focuses on the last step of the pathway which is the glycosylation of digitoxigenin by a uridine 5'-diphospho-glycosyltransferase (UGT) in Digitalis. Glycosylation in the Digitoxin and Digoxin pathway plays a role in how the compound gets metabolized within in the plant and affects its pharmacokinetic properties. Using tobacco transient expression techniques and analysis of metabolites through liquid chromatography mass-spectrometry, this study identifies a UGT that is capable of adding glucose moieties to digitoxigenin.
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