Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis

Elongation of very long-chain fatty acid (Elovl) proteins are key enzymes that catalyze the rate-limiting step in the fatty acid elongation pathway. The most recently discovered member of the Elovl family, Elovl8, has been proposed to be a fish-specific elongase with two gene paralogs described in t...

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Main Authors: Shouxiang Sun, Yumei Wang, Pei-Tian Goh, Mónica Lopes-Marques, L. Filipe C. Castro, Óscar Monroig, Meng-Kiat Kuah, Xiaojuan Cao, Alexander Chong Shu-Chien, Jian Gao
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/12/8/1287
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author Shouxiang Sun
Yumei Wang
Pei-Tian Goh
Mónica Lopes-Marques
L. Filipe C. Castro
Óscar Monroig
Meng-Kiat Kuah
Xiaojuan Cao
Alexander Chong Shu-Chien
Jian Gao
author_facet Shouxiang Sun
Yumei Wang
Pei-Tian Goh
Mónica Lopes-Marques
L. Filipe C. Castro
Óscar Monroig
Meng-Kiat Kuah
Xiaojuan Cao
Alexander Chong Shu-Chien
Jian Gao
author_sort Shouxiang Sun
collection DOAJ
description Elongation of very long-chain fatty acid (Elovl) proteins are key enzymes that catalyze the rate-limiting step in the fatty acid elongation pathway. The most recently discovered member of the Elovl family, Elovl8, has been proposed to be a fish-specific elongase with two gene paralogs described in teleosts. However, the biological functions of Elovl8 are still to be elucidated. In this study, we showed that in contrast to previous findings, <i>elovl8</i> is not unique to teleosts, but displays a rather unique and ample phylogenetic distribution. For functional determination, we generated <i>elovl8a</i> (<i>elovl8a<sup>−</sup></i><sup>/<i>−</i></sup>) and <i>elovl8b</i> (<i>elovl8b<sup>−</sup></i><sup>/<i>−</i></sup>) zebrafish using CRISPR/Cas9 technology. Fatty acid composition in vivo and zebrafish liver cell experiments suggest that the substrate preference of Elovl8 overlapped with other existing Elovl enzymes. Zebrafish Elovl8a could elongate the polyunsaturated fatty acids (PUFAs) C18:2n-6 and C18:3n-3 to C20:2n-6 and C20:3n-3, respectively. Along with PUFA, zebrafish Elovl8b also showed the capacity to elongate C18:0 and C20:1. Gene expression quantification suggests that Elovl8a and Elovl8b may play a potentially important role in fatty acid biosynthesis. Overall, our results provide novel insights into the function of Elovl8a and Elovl8b, representing additional fatty acid elongases not previously described in chordates.
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spelling doaj.art-040e9a751d744a6e9abd33361b4d57c02023-11-22T07:47:13ZengMDPI AGGenes2073-44252021-08-01128128710.3390/genes12081287Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid BiosynthesisShouxiang Sun0Yumei Wang1Pei-Tian Goh2Mónica Lopes-Marques3L. Filipe C. Castro4Óscar Monroig5Meng-Kiat Kuah6Xiaojuan Cao7Alexander Chong Shu-Chien8Jian Gao9Key Lab of Freshwater Animal Breeding, College of Fisheries, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, ChinaKey Lab of Freshwater Animal Breeding, College of Fisheries, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, ChinaCenter for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas 11800, Penang, MalaysiaCIIMAR/CIMAR—Interdisciplinary Center of Marine and Environmental Research, University of Porto, 4099002 Porto, PortugalCIIMAR/CIMAR—Interdisciplinary Center of Marine and Environmental Research, University of Porto, 4099002 Porto, PortugalInstituto de Acuicultura Torre de la Sal (IATS-CSIC), Ribera de Cabanes, 12595 Castellon, SpainCenter for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas 11800, Penang, MalaysiaKey Lab of Freshwater Animal Breeding, College of Fisheries, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, ChinaCenter for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas 11800, Penang, MalaysiaKey Lab of Freshwater Animal Breeding, College of Fisheries, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, ChinaElongation of very long-chain fatty acid (Elovl) proteins are key enzymes that catalyze the rate-limiting step in the fatty acid elongation pathway. The most recently discovered member of the Elovl family, Elovl8, has been proposed to be a fish-specific elongase with two gene paralogs described in teleosts. However, the biological functions of Elovl8 are still to be elucidated. In this study, we showed that in contrast to previous findings, <i>elovl8</i> is not unique to teleosts, but displays a rather unique and ample phylogenetic distribution. For functional determination, we generated <i>elovl8a</i> (<i>elovl8a<sup>−</sup></i><sup>/<i>−</i></sup>) and <i>elovl8b</i> (<i>elovl8b<sup>−</sup></i><sup>/<i>−</i></sup>) zebrafish using CRISPR/Cas9 technology. Fatty acid composition in vivo and zebrafish liver cell experiments suggest that the substrate preference of Elovl8 overlapped with other existing Elovl enzymes. Zebrafish Elovl8a could elongate the polyunsaturated fatty acids (PUFAs) C18:2n-6 and C18:3n-3 to C20:2n-6 and C20:3n-3, respectively. Along with PUFA, zebrafish Elovl8b also showed the capacity to elongate C18:0 and C20:1. Gene expression quantification suggests that Elovl8a and Elovl8b may play a potentially important role in fatty acid biosynthesis. Overall, our results provide novel insights into the function of Elovl8a and Elovl8b, representing additional fatty acid elongases not previously described in chordates.https://www.mdpi.com/2073-4425/12/8/1287<i>elovl8</i>gene knockoutzebrafishfatty acid synthesis
spellingShingle Shouxiang Sun
Yumei Wang
Pei-Tian Goh
Mónica Lopes-Marques
L. Filipe C. Castro
Óscar Monroig
Meng-Kiat Kuah
Xiaojuan Cao
Alexander Chong Shu-Chien
Jian Gao
Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
Genes
<i>elovl8</i>
gene knockout
zebrafish
fatty acid synthesis
title Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
title_full Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
title_fullStr Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
title_full_unstemmed Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
title_short Evolution and Functional Characteristics of the Novel <i>elovl8</i> That Play Pivotal Roles in Fatty Acid Biosynthesis
title_sort evolution and functional characteristics of the novel i elovl8 i that play pivotal roles in fatty acid biosynthesis
topic <i>elovl8</i>
gene knockout
zebrafish
fatty acid synthesis
url https://www.mdpi.com/2073-4425/12/8/1287
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