title: A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
abstract: Arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are the most biologically active polyunsaturated fatty acids, but their biosyntheses in mammals are very limited. The biosynthesis of DHA is the most difficult, because this undergoes the Sprecher pathway--a further elongation step from docosapentaenoic acid (DPA), a Δ6-desaturase acting on a C24 fatty acid substrate followed by a peroxisomal chain shortening step. This paper reports the successful heterologous expression of two non-mammalian genes (with modification of codon usage), coding for Euglena gracilis Δ4-desaturase and Siganus canaliculatus Δ4-desaturase respectively, in mammalian cells (HEK293 cell line). Both of the Δ4-desaturases can efficiently function, directly converting DPA into DHA. Moreover, the cooperation of the E. gracilis Δ4-desaturase with C. elegans Δ15-desaturase (able to convert a number of n-6 PUFAs to their corresponding n-3 PUFAs) in transgenic HEK293 cells made a more desirable fatty acid composition--a drastically reduced n-6/n-3 PUFAs ratio and a high level of DHA as well as EPA and ARA. Our findings provide a basis for potential applications of the gene constructs for expression of Δ15/Δ4-desaturases in transgenic livestock to produce such a fatty acid profile in the related products, which certainly will bring benefit to human health.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Guiming
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ou
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Sun
authors.affiliation: Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi, Heilongjiang, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Kunfu
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Fang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
authors.forename: Tangdong
authors.initials: T
authors.lastname: Ge
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D002849:Chromatography, Gas; D017931:DNA Primers / Q000235:genetics; D005056:Euglena gracilis / Q000201:enzymology / Q000235:genetics*; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005399:Fishes / Q000235:genetics*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases; C094563:delta-15 desaturase; C434953:delta-4 fatty acid desaturase