Enhanced Production of Docosahexaenoic Acid in Mammalian Cells

Docosahexaenoic acid (DHA), one of the important polyunsaturated fatty acids (PUFA) with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA). However, the acumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased prodution of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Delta 4 desaturase was heterologously expressed in chinese hamster ovary (CHO) cells, and simultaneously, mouse Delta 6-desaturase and Delta 5-desaturase were overexpressed. The results demonstrated that the overexpression of Delta 6/Delta 5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA) which in turn get converted into DHA directly and efficiently by the heterologously expressed Delta 4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA.