The molecular basis of long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis in Atlantic salmon (Salmo salar L): In vivo functions, functional redundancy and transcriptional regulation of LC-PUFA biosynthetic enzymes

Abstract

Farmed Atlantic salmon (Salmo salar L.) is a rich source of the omega-3 fatty acids (ω-3 FA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, which are linked to health benefits in humans including prevention of cardiovascular and inflammatory diseases. Salmon aquaculture has experienced steady growth over the past years partly due to use of formulated diets (aquafeeds) that contain essential micro- and macronutrients necessary for optimal growth. Notably, however, marine ingredients like fish oils (FOs) have been reduced significantly in aquafeeds in recent years, and partially substituted with more sustainable terrestrial ingredients such as vegetable oils that are devoid of the nutritionally beneficial EPA and DHA; a practice that ultimately reduce ω-3 FA content in farmed salmon. My thesis sought to provide detailed understanding of molecular mechanisms underlying EPA and DHA biosynthesis and regulation in salmon. Using the recently discovered CRISPR/Cas9 genome-editing technology, key enzymes for ω-3 FA synthesis were studied, including fatty acyl desaturases (Fads2) and elongases of very long chain fatty acids (Elovls).

We have successfully generated gene-edited Fads2 and Elovl salmon, and have identified salmon Elovl2 and Δ6 (delta-6) Fads2-a as crucial enzymes for salmon ω-3 FA biosynthesis. This is highly beneficial to the salmon industry, as the elovl2 and Δ6fads2-a genes can serve as markers for genetic selection; thus, providing a means of breeding salmon with inherently high elovl2 and Δ6fads2-a expression and enhanced synthesis of EPA and DHA. We have also identified key regulatory network of proteins important for the control of salmon ω-3 FA synthesis. Findings from our study also underpin vegetable oils as important sustainable raw materials for aquafeed formulation, as salmon fed vegetable oils showed no adverse effects on growth. This thesis provides novel mechanistic knowledge of Atlantic salmon ω-3 FA biosynthesis and nutritional adaptation.