We report the production of two very long chain polyunsaturated fatty acids, arachidonic acid (AA) and eicosapentaenoic acid (EPA), in substantial quantities in a higher plant. This was achieved using genes encoding enzymes participating in the omega3/6 Delta8 -desaturation biosynthetic pathways for the formation of C20 polyunsaturated fatty acids. Arabidopsis thaliana was transformed sequentially with genes encoding a Delta9 -specific elongating activity from Isochrysis galbana, a Delta8 -desaturase from Euglena gracilis and a Delta5 -desaturase from Mortierella alpina. Instrumental in the successful reconstitution of these C20 polyunsaturated fatty acid biosynthetic pathways was the I. galbana C18-Delta9 -elongating activity, which may bypass rate-limiting steps present in the conventional Delta6 -desaturase/elongase pathways. The accumulation of EPA and AA in transgenic plants is a breakthrough in the search for alternative sustainable sources of fish oils.

Isochrysis galbana, a marine prymnesiophyte micro-

Dietary omega3-polyunsaturated fatty acids are thought to influence the risk of Alzheimer's disease (AD), and supplemental docosahexaenoic acid (DHA; 22:6n-3) has been reported to reduce neurodegeneration in mouse models of AD. We have analysed the fatty acid composition of frontal, temporal and parietal neocortex in 58 normal and 114 AD brains. Significant reductions were found for stearic acid (18:0) in frontal and temporal cortex and arachidonic acid (20:4n-6) in temporal cortex in AD, and increases in oleic acid in frontal and temporal cortex (18:1n-9) and palmitic acid (16:0) in parietal cortex. DHA level varied more in AD than controls but the mean values were not significantly different. Fatty acid composition was not related to APOE genotype, age, gender or post-mortem delay. Further research is needed to distinguish between alterations that are secondary to AD and those that contribute to the disease process.

A cDNA isolated from the prymnesiophyte micro-alga Isochrysis galbana, designated IgASE1, encodes a fatty acid elongating component that is specific for linoleic acid (C18:2n-6) and a-linolenic acid (C18:3n-3). Constitutive expression of IgASE1 in Arabidopsis resulted in the accumulation of eicosadienoic acid (EDA; C20:2n-6) and eicosatrienoic acid (ETrA; C20:3n-3) in all tissues examined, with no visible effects on plant morphology. Positional analysis of the various lipid classes indicated that these novel fatty acids were largely excluded from the sn-2 position of chloroplast galactolipids and seed triacylglycerol, whereas they were enriched in the same position in phosphatidylcholine. EDA and ETrA are precursors of arachidonic acid (C20:4n-6), eicosapentaenoic acid (C20:5n-3), and docosahexaenoic acid (C22:6n-3) synthesized via the so-called v6 D8 desaturase and v3 D8 desaturase biosynthetic pathways, respectively. The synthesis of significant quantities of EDA and ETrA in a higher plant is therefore a key step in the production of very long chain polyunsaturated fatty acid in oil-seed species. The results are further discussed in terms of prokaryotic and eukaryotic pathways of lipid synthesis in plants.The very long chain polyunsaturated fatty acids (VLCPUFAs), arachidonic acid (AA; C20:4n-6), docosahexaenoic acid (DHA; C22:6n-3), and eicosapentaenoic acid (EPA; C20:5n-3) are considered to have profound effects on cell function and development. The reduction in nonfatal and fatal cardiovascular events that is associated with the consumption of EPA and DHA may be due to the stabilization of atherosclerotic plaques (Thies et al., 2003). AA and DHA are considered to be important in pre-and postnatal development (Crawford, 2000; for review, see Lauritzen et al., 2001). Such VLCPUFAs are also precursors of the physiologically active prostaglandins, thromboxanes, and leukotrienes. No higher plants contain these fatty acids and hence it is considered desirable to genetically engineer the capacity to synthesize them in oilseed species and so provide an important source for the nutraceutical/pharmaceutical industries.Isochrysis galbana is a marine microalga that is rich in DHA and EPA (Lopez et al., 1994). Recently we isolated and characterized a cDNA from I. galbana, which encodes a novel fatty acid elongase component designated IgASE1 (Qi et al., 2002(Qi et al., , 2003. Transgenic yeastexpressing IgASE1 converted linoleic acid (LA; C18:2n-6) and a-linolenic acid (ALA; C18:3n-3) to eicosadienoic acid (EDA; C20:2n-6) and eicosatrienoic acid (ETrA; C20:3n-3), respectively (Qi et al., 2002). The substrate specificity of IgASE1 is consistent with it catalyzing the condensation reaction of fatty acid elongation (Qi et al., 2003). We have further suggested (Qi et al., 2002(Qi et al., , 2003 that the IgASE1 elongating activity is the first committed step in VLCPUFA synthesis and hence AA, EPA, and DHA formation via the so-called v3 D8 and v6 D8 pathways, respectively ( Fig. 1; Nichols and Appleby, 1969).Here we report the...