A More Desirable Balanced Polyunsaturated Fatty Acid Composition Achieved by Heterologous Expression of [DELTA]15/[DELTA]4 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 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.