title: Vertebrate fatty acyl desaturase with Δ4 activity.
abstract: 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 182n - 6 to produce 183n - 6 that is elongated to 203n - 6 followed by Δ5 desaturation. Synthesis of EPA from 183n - 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 225n - 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 225n - 3 followed by Δ4 desaturation, as well as the more complicated pathway as described above.
authors.affiliation: Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, Guangdong 515063, China. yyli@stu.edu.cn
authors.forename: Yuanyou
authors.initials: Y
authors.lastname: Li
authors.forename: Oscar
authors.initials: O
authors.lastname: Monroig
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Shuqi
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Zheng
authors.forename: James R
authors.initials: JR
authors.lastname: Dick
authors.forename: Cuihong
authors.initials: C
authors.lastname: You
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Tocher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010473:Perciformes / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny
chemical_list: D018076:DNA, Complementary; D044943:Fatty Acid Desaturases; C434953:delta-4 fatty acid desaturase
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