科研之友
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摘要
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 Delta 6-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 Delta 4-desaturase and Siganus canaliculatus Delta 4-desaturase respectively, in mammalian cells (HEK293 cell line). Both of the Delta 4-desaturases can efficiently function, directly converting DPA into DHA. Moreover, the cooperation of the E. gracilis Delta 4-desaturase with C. elegans Delta 15-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 Delta 15/Delta 4-desaturases in transgenic livestock to produce such a fatty acid profile in the related products, which certainly will bring benefit to human health.
