哺乳动物细胞多不饱和脂肪酸合成酶系的重建将亚油酸代谢转变为二十二碳六烯酸

Reconstitution of polyunsaturated fatty acid synthesis enzymes in mammalian cells to convert LA to DHA

摘要:

二十二碳六烯酸 (DHA, 22:6n-3) 是一种长度为22个碳原子且含有6个双键的ω-3系多不饱和脂肪酸，在人体中具有重要生物学功能。人体及其他哺乳动物体内只能合成少量的DHA，更多的需求必须从食物中获取。然而，DHA的天然资源 (主要是深海鱼类等海洋产品) 日趋枯竭，开发新型资源以满足不断扩大的市场需求势在必行。本研究利用转基因技术，在哺乳动物细胞中使Δ6和Δ5脂肪酸去饱和酶以及Δ6和Δ5脂肪酸延长酶超表达，同时表达来源于秀丽隐杆线虫Caenorhabditis elegans的Δ15去饱和酶和小眼虫Euglena gracilis的Δ4去饱和酶，结果表明，这6种酶的表达或超表达能将ω-6系的亚油酸 (LA,18:2n-6) 有效地转化为DHA (22:6n-3)，后者的含量从对照组的16.74%提高到实验组的25.3%。本研究的策略及技术路线为将来利用遗传改造的哺乳动物生产珍稀的DHA (22:6n-3) 等长链多不饱和脂肪酸产品提供了重要的启示。

Abstract:

DHA (22:6n-3) is a ω-3 polyunsaturated fatty acid with 22 carbon atoms and?6 double bonds, which has important biological functions in human body. Human and other mammals synthesize only limited amounts of DHA, more requirements must be satisfied from food resources. However, the natural resources of DHA (Mainly deep-sea fish and other marine products) are prone to depletion. New resources development is still insufficient to satisfy the growing market demand. Previous studies have revealed that the mammals can increase the synthesis of DHA and other long-chain polyunsaturated fatty acids after transgenic procedures. In this study, mammalian cells were transfected with Δ6, Δ5 desaturase, Δ6, Δ5 elongase, Δ15 desaturase (Isolated from nematode Caenorhabditis elegans) and Δ4 desaturase (Isolated from Euglena gracilis), simultaneously. Results show that the expression or overexpression of these 6 enzymes is capable of conversion of the ω-6 linoleic acid (LA, 18:2n-6) in DHA (22:6n-3). DHA content has increased from 16.74% in the control group to 25.3% in the experimental group. The strategy and related technology in our research provided important data for future production the valuable DHA (22:6n-3) by using genetically modified animals.