Assessment of Fatty Acid Desaturase (Fads2) Structure-Function Properties in Fish in the Context of Environmental Adaptations and as a Target for Genetic Engineering

Abstract

Fatty acid desaturase 2 (Fads2) is the key enzyme of long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. Endogenous production of these biomolecules in vertebrates, if present, is insufficient to meet demand. Hence, LC-PUFA are considered as conditionally essential. At present, however, LC-PUFA are globally limited nutrients due to anthropogenic factors. Research attention has therefore been paid to finding ways to maximize endogenous LC-PUFA production, especially in production species, whereby deeper knowledge on molecular mechanisms of enzymatic steps involved is being generated. This review first briefly informs about the milestones in the history of LC-PUFA essentiality exploration before it focuses on the main aim-to highlight the fascinating Fads2 potential to play roles fundamental to adaptation to novel environmental conditions. Investigations are summarized to elucidate on the evolutionary history of fish Fads2, providing an explanation for the remarkable plasticity of this enzyme in fish. Furthermore, structural implications of Fads2 substrate specificity are discussed and some relevant studies performed on organisms other than fish are mentioned in cases when such studies have to date not been conducted on fish models. The importance of Fads2 in the context of growing aquaculture demand and dwindling LC-PUFA supply is depicted and a few remedies in the form of genetic engineering to improve endogenous production of these biomolecules are outlined.

Keywords: AA; DHA; EPA; LC-PUFA; essential fatty acid; fatty acyl desaturase; fish; health; long-chain polyunsaturated fatty acid; transgene; Δ6 - desaturase; ω3; ω6.

Figure 1

Biosynthetic pathways of long-chain (≥ C₂₀) polyunsaturated fatty acids (LC-PUFAs) of ω3 and ω6 families from dietary essential α-linolenic (ALA, 18:3n-3) and linoleic (LA, 18:2n-6) acids, respectively, by elongation and desaturation reactions. Adapted from (Carmona-Antoñanzas et al., 2011; Monroig et al., 2011; Sprecher, 2000; Voss et al., 1991); modified after (Trattner, 2009; Vestergeren, 2014; Yan, 2016).

Figure 2

Sequence logo of histidine boxes in membrane associated front-end desaturases such as Δ6 Fads2. The high of letters corresponds to the occurrence probability. Adapted from (Sayanova, 2001). Modified after (Hashimoto, 2007).

Figure 3

The predicted topology model of Δ6 Fads2. The black solid rectangles indicate boundaries of domains. Four alpha-helices span the membrane. The blue lines and blue dots indicate the areas and sites implicated in substrate specificity, red lines and red dots indicate the areas and sites important for catalytic activity, respectively. ER lumen: endoplasmic reticulum lumen. HIS I, HIS II and HIS III: histidine rich motifs. Modified from (Shi et al., 2018).