A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.

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...

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Autores principales: Guiming Zhu, Qin Ou, Tao Zhang, Xudong Jiang, Guozhi Sun, Ning Zhang, Kunfu Wang, Heng Fang, Mingfu Wang, Jie Sun, Tangdong Ge
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spelling oai:doaj.org-article:bb061e6a47ed4815992ba415297a94652021-11-18T08:39:16ZA more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.1932-620310.1371/journal.pone.0084871https://doaj.org/article/bb061e6a47ed4815992ba415297a94652013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24391980/?tool=EBIhttps://doaj.org/toc/1932-6203Arachidonic (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.Guiming ZhuQin OuTao ZhangXudong JiangGuozhi SunNing ZhangKunfu WangHeng FangMingfu WangJie SunTangdong GePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84871 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Guiming Zhu
Qin Ou
Tao Zhang
Xudong Jiang
Guozhi Sun
Ning Zhang
Kunfu Wang
Heng Fang
Mingfu Wang
Jie Sun
Tangdong Ge
A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
description 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.
format article
author Guiming Zhu
Qin Ou
Tao Zhang
Xudong Jiang
Guozhi Sun
Ning Zhang
Kunfu Wang
Heng Fang
Mingfu Wang
Jie Sun
Tangdong Ge
author_facet Guiming Zhu
Qin Ou
Tao Zhang
Xudong Jiang
Guozhi Sun
Ning Zhang
Kunfu Wang
Heng Fang
Mingfu Wang
Jie Sun
Tangdong Ge
author_sort Guiming Zhu
title A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
title_short A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
title_full A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
title_fullStr A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
title_full_unstemmed A more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of Δ15/Δ4 desaturases in mammalian cells.
title_sort more desirable balanced polyunsaturated fatty acid composition achieved by heterologous expression of δ15/δ4 desaturases in mammalian cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/bb061e6a47ed4815992ba415297a9465
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