Molecular analysis of the mechanisms underlying the biosynthesis of very long chain polyunsaturated fatty acids

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Very long chain polyunsaturated fatty acids (VLCPUFAs) such as arachidonic acid (20:4n 6, ARA), eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n 3, DHA) are essential components of mammalian cell membranes and precursors of biologically active compounds, such as mammalian eicosanoids and docosanoids. Dietary VLCPUFAs not only provide protection against common chronic diseases such as cardiovascular diseases, metabolic syndrome and inflammatory disorders, but can also enhance the performance of the eyes, brain and nervous system. The current sources for VLCPUFA supplements are oils from fish and microbes. However, shrinking fish populations and possible contaminants in fish oil, along with the low yields and high costs of oil extraction from microbial sources are making the economic sustainability of these traditional sources questionable. In the past few years, research workers have explored the use of transgenic plants as an alternative source for VLCPUFAs. Genes encoding desaturases and elongases involved in the biosynthesis of VLCPUFAs have been identified from microalgae and fungi, and successfully introduced into plants. However, transgenic plants expressing these genes produced VLCPUFAs at a level much lower than that found in native microorganisms, implying additional factors besides desaturases and elongases per se are required for the synthesis and accumulation of higher levels of VLCPUFAs in heterologous systems. The goal of this research is to identify and characterize these factors in the native Thraustochytrium sp, a single cellular protist capable of accumulating substantial amounts of VLCPUFAs in triacylglycerols. Specifically, we will identify and characterize acyltransferases, which facilitate polyunsaturated acyl flux, and cofactors of the condensing enzyme/elongase, which assist in the elongation of polyunsaturated fatty acids. Achieving these goals will significantly contribute to our understanding of the mechanisms underlying the synthesis, assembly and accumulation of VLCPUFAs, and will provide strategies for the transgenic production of VLCPUFAs in oilseed crops.