Sunday, May 4, 2025
5/4/2025
Identification and Characterization of Carotenoid Repair Enzymes - DESCRIPTION (provided by applicant): Dietary carotenoids are associated with many health benefits, including decreased rates of cancer and inflammatory disease. More importantly, pro-vitamin A carotenoids (such as β-carotene) are essential for prevention of vitamin A deficiency (VAD), a global health problem causing blindness, greater susceptibility to disease, and increased mortality. Because of their health-promoting roles, substantial progress has been made in the metabolic engineering of carotenoids in plant-based foods. Most famously, golden rice was engineered with high levels of β-carotene to aid prevention of VAD, which impacts hundreds of millions of people worldwide. Other carotenoids are also the target of metabolic engineering research, with similar, health-focused goals. The roles of carotenoids and their Apo carotenoid derivatives (e.g. vitamin A) are mediated by multiple biochemical mechanisms including light absorption, electron transfer, and isomerization and quenching of reactive oxygen species (ROS). In these roles, carotenoids are exposed to high-energy and oxygen-rich environments where they react forming carotenoid damage products that are hazardous to life. As an example, β-carotene in plants is fundamental for protection of photosystem II against ROS. Damage of this carotenoid generates a highly reactive pro-oxidant that decreases photosynthetic efficiency, negatively impacting crop yield. In humans, vitamin A damage products cause macular degeneration, while oxidative damaged β-carotene is linked to an increased incidence of lung and stomach cancers. Although the unavoidable formation of carotenoid damage products is well documented, their accumulation in non-stressed photosynthetic tissues is not. Interestingly, non-photosynthetic tissues of plants (where carotenoids are not essential) often accumulate carotenoid damage products under non-stress conditions. This is problematic for the metabolic engineering of carotenoids, as edible non-photosynthetic tissues are the target of these bio-fortification efforts. The formation of damage products in these tissues not only decreases the carotenoid content of food, but also hastens spoilage. The lack of accumulated carotenoid damage products in photosynthetic tissues -- where carotenoids are essential, but ROS levels are highest -- suggests the presence of an, as yet undefined, network of repair enzymes that mend damaged carotenoids. My recent publication uncovering a gene that is inversely correlated with the accumulation of oxidative damaged β- carotene in photosynthetic tissues strengthens this hypothesis. The proposed pilot project will characterize the function of two putative carotenoid repair enzymes. The results of this research will greatly benefit the stable engineering of carotenoids in plant-based foods for the prevention of disease. Additionally, an important part of this project is my professional development as a PI. As such, I sought out a highly successful mentor to guide me during this early stage of my career by advising on research direction and dissemination, collaborative opportunities and acquisition of research funding.
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