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Vertebrate fatty acyl desaturase with Δ4 activity

Li, Yuanyou, Monroig, Oscar, Zhang, Liang, Wang, Shuqi, Zheng, Xiaozhong, Dick, James R., You, Cuihong, Tocher, Douglas R.
Proceedings of the National Academy of Sciences of the United States of America 2010 v.107 no.39 pp. 16840-16845
Danio rerio, Papio, Saccharomyces cerevisiae, Siganus canaliculatus, biosynthesis, complementary DNA, docosahexaenoic acid, eicosapentaenoic acid, enzymes, fish, genes, herbivores, heterologous gene expression, long chain polyunsaturated fatty acids, mammals, proteins, yeasts
Biosynthesis of the highly biologically active long-chain polyunsaturated fatty acids, arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids, in vertebrates requires the introduction of up to three double bonds catalyzed by fatty acyl desaturases (Fad). Synthesis of ARA is achieved by Δ6 desaturation of 18:2n - 6 to produce 18:3n - 6 that is elongated to 20:3n - 6 followed by Δ5 desaturation. Synthesis of EPA from 18:3n - 3 requires the same enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further elongations, a second Δ6 desaturation and a peroxisomal chain shortening step. This paper describes cDNAs, fad1 and fad2, isolated from the herbivorous, marine teleost fish (Siganus canaliculatus) with high similarity to mammalian Fad proteins. Functional characterization of the cDNAs by heterologous expression in the yeast Saccharomyces cerevisiae showed that Fad1 was a bifunctional Δ6/Δ5 Fad. Previously, functional dual specificity in vertebrates had been demonstrated for a zebrafish Danio rerio Fad and baboon Fad, so the present report suggests bifunctionality may be more widespread in vertebrates. However, Fad2 conferred on the yeast the ability to convert 22:5n - 3 to DHA indicating that this S. canaliculatus gene encoded an enzyme having Δ4 Fad activity. This is a unique report of a Fad with Δ4 activity in any vertebrate species and indicates that there are two possible mechanisms for DHA biosynthesis, a direct route involving elongation of EPA to 22:5n - 3 followed by Δ4 desaturation, as well as the more complicated pathway as described above.