Biocatalytic production of precursors to lutein and zeaxanthin to address age-related macular degeneration

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Project Summary Atrophic (“dry”) age related macular degeneration (AMD) is the leading cause of severe loss of vision for those over age 50. Dietary supplements containing lutein and zeaxanthin are recommended by the NEI for those at risk of late AMD. There has been a corresponding growth in demand for these two xanthophylls. Lutein and zeaxanthin are currently sourced from marigolds grown mostly overseas. The purity and reliability of these sources is highly variable. A synthetic source for lutein would ensure quality and secure adequate supplies for the predicted ever increasing demand for this eye health product. However, there is no commercially viable synthesis of the natural, enantiomerically correct form (3R,3'R,6'R) of lutein. This barrier prevents the development of a secure, reliable, and scalable source for lutein. Furthermore, the unavailability of pure synthetic isomers prevents definitive experimental studies on their relative effectiveness. The current proposal seeks to remove this barrier by demonstrating a reliable synthesis of enantiomerically correct lutein and zeaxanthin. The hypothesis is that highly enantiomerically-enriched (4S)-(+)-ipsdienol or (4R)-(–)-ipsdienol can be used to synthesize nature identical lutein or zeaxanthin, respectively. We have developed an innovative enzymatic process that eliminates the current prohibitively high cost to produce enantiomerically-enriched ipsdienol. Furthermore, we will optimize production of recombinant enzymes used in our process, further reducing costs. Completion of this Phase I project will show the practicality of new production methods for lutein and zeaxanthin. This should lead to significant price reductions for highly pure forms of these chemicals, thus enabling further research into their protective properties. Phase II efforts will confirm the bioactivity of our products and confirm that possible contaminants in natural preparations do not confer the protective effects assigned to lutein and zeaxanthin. We will also seek to expand the potential market for these chemicals as food supplements.