Classification and substrate head-group specificity of membrane fatty acid desaturases

Abstract

Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure–function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases. In this work, we have used sequence similarity networks to investigate the similarity among over 5000 related membrane fatty acid desaturase sequences, leading to a detailed classification of the superfamily, families and subfamilies with regard to their function and substrate head-group specificity. This work will facilitate rapid prediction of the function and specificity of new and existing sequences, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.

Plastidic Δ6 Fatty-Acid Desaturases with Distinctive Substrate Specificity Regulate the Pool of C18-PUFAs in the Ancestral Picoalga Ostreococcus tauri

“…Substrate specificity of O. tauri Δ6-DES DES specificity relies on intricate substrate features, including the acyl-chain position, length, unsaturation features, and the acyl-carrier nature (Heilmann et al, 2004a;Li, D et al, 2016). Domain swapping between DES of distinctive specificity, together with further amino acid mutation, could highlight the primary importance of His-Box and surrounding region for front-end desaturase activity and substrate specificity (Song et al, 2014;Li, D et al, 2016;Watanabe et al, 2016). However, neither the exact molecular features underlying DES (regio)specificity nor the hierarchical importance of the substrate features are yet clearly identified.…”

“…The discovery of plastidic Δ6-DES and the impact of their overexpression in O. tauri points out the requirement of tight regulation of the C18-PUFA pool in microalgae. (Lee et al, 2016;Li, D et al, 2016). The strategy used is this study further illustrates how overexpression in several host systems of distinctive glycerolipid composition gives insight into DES substrate specificity.…”

Plastidic Δ6 fatty-acid desaturases with distinctive substrate specificity regulate the pool of c18-pufas in the ancestral picoalgaostreococcus tauri

“…DES specificity relies on intricate substrate features, including the acyl-chain position, length, unsaturation features, and the acyl-carrier nature (Heilmann et al ., 2004a; Li, D et al ., 2016). Domain swapping between DES of distinctive specificity, together with further amino acid mutation, could highlight the primary importance of His-Box and surrounding region for front-end desaturase activity and substrate specificity (Song et al ., 2014; Li, D et al ., 2016; Watanabe et al ., 2016).…”

Integral Membrane Fatty Acid Desaturases: A Review of Biochemical, Structural, and Biotechnological Advances

“…The authors concluded “Further work to characterize these abundant proteins will be necessary” but could not give any new indication regarding head group specificity. [ 108 ]…”