Owens, Daniel

• Ph.D., Virginia Tech

• B.S., East Tennessee State University

Plants are in continuous competition for water, nutrients, and other sources of nourishment. This in turn has caused each species to develop a unique array of phytochemicals as they attempt to increase their fitness in continual "chemical warfare" as they compete for resources. This has led to the evolution of a unique complement of associated phytochemicals for each species that have possible medicinal and commercial value. As each of these chemicals has resulted from unique evolutionary forces they have the additional benefit of potential of acting at previously unconsidered and/or unidentified molecular target sites. Antioxidant and/or anti-inflammatory phytochemicals are routinely identified as the primary active constituents of medicinal plants that contribute to their abilities to protect against ailments and chronic illnesses such as cardiovascular disease and different cancers. Antioxidants act to reduce damaging excess reactive oxygen species (ROS) to maintain redox balance and prevent cellular damage. Humans have native antioxidant systems to protect against free radical damage, but these mechanisms are often insufficient to control for improper spatial and temporal production of ROS. This problem is further exacerbated when ROS synthesis is stimulated by the presence of factors  such as a diet high in polyunsaturated fats, cigarette smoke and other air pollutants, UV radiation, and inflammation. In cases where the native systems are inadequate, additional antioxidants supplied in the diet or as pharmaceutical supplements are necessary to prevent long term damage due to the cumulative effects of oxidative damage. Plant antioxidants can prevent the production of ROS by chelating trace elements and/or inhibiting enzymes required for their production, directly scavenging ROS, and influencing in vivo antioxidant defenses are established mechanisms of antioxidant activity. As part of this project, we intend to identify, isolate, and characterize medicinally significant phytochemicals from previously understudied plant species.

Increasing the yields of health-promoting antioxidant flavonoids for nutraceutical and medicinal applications is another objective of this project. Flavonoids have antioxidant, anti-inflammation and anti-allergenic properties that provide pharmaceutical activity against infection and disease (e.g. heart disease and certain cancers) when consumed in the diet. The biochemical pathways that lead to the biosynthesis of the flavonoid core structure have been extensively studied in the model plant Arabidopsis demonstrating that metabolic organization and metabolon (unique fluid three-dimensional arrangements of enzymes) formation have a significant impact on the amounts and types of flavonoids that accumulate. C. sinesis (orange) is a particularly suitable model system in which to base flavonoid metabolon studies as it is used to produce popularly consumed food products, uniquely accumulates medicinal early flavonoids and the genome sequence for the species that are now available. Furthermore, the blood oranges, unique orange cultivars that accumulate anthocyanins (late flavonoids), provide a rare opportunity to examine how the additional enzymes required to produce anthocyanins have differential regulation and impacts on flavonoid metabolon organization in the same species and how this might be manipulated to improve accumulation of medicinal flavonoids of interest. What remains unknown is how flavonoid enzymes are organized to form a metabolon in species that accumulate early flavonoids and the role played by derivatizing enzymes such as glycosyl-transferases (GTs). The central hypothesis is that accumulation of orange flavonoid end products depends upon formation of a metabolon. This hypothesis was formed by previous analysis of the Arabidopsis flavonoid metabolon, studies of flavonoid glycosylation and preliminary yeast-2-hybrid interaction data. There is a critical need to determine the enzymology and metabolic orgnaization of a flavonoid metabolon in a nutrionally significant plant species with these characteristics to identify targets for improving content and quality of flavonoids for medicinal use.