A novel Tetrahymena thermophila sterol C-22 desaturase belongs to the fatty acid hydroxylase/desaturase superfamily

Sterols in eukaryotic cells play important roles in modulating membrane fluidity and in cell signaling and trafficking. During evolution, a combination of gene losses and acquisitions gave rise to an extraordinary diversity of sterols in different organisms. The sterol C-22 desaturase identified in...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 298; no. 10; p. 102397
Main Authors:	Sanchez Granel, María L., Siburu, Nicolás G., Fricska, Annamária, Maldonado, Lucas L., Gargiulo, Laura B., Nudel, Clara B., Uttaro, Antonio D., Nusblat, Alejandro D.
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 01-10-2022 American Society for Biochemistry and Molecular Biology
Subjects:	cholesterol ciliates cytochrome P450 endoplasmic reticulum fatty acid fatty acid desaturase family gene duplication lipid protein evolution sterols protein evolution ciliates fatty acid FAD fatty acid desaturase family NISE sterols cytochrome P450 lipid CUB HGT gene duplication FAHD cholesterol endoplasmic reticulum
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Summary:	Sterols in eukaryotic cells play important roles in modulating membrane fluidity and in cell signaling and trafficking. During evolution, a combination of gene losses and acquisitions gave rise to an extraordinary diversity of sterols in different organisms. The sterol C-22 desaturase identified in plants and fungi as a cytochrome P-450 monooxygenase evolved from the first eukaryotic cytochrome P450 and was lost in many lineages. Although the ciliate Tetrahymena thermophila desaturates sterols at the C-22 position, no cytochrome P-450 orthologs are present in the genome. Here, we aim to identify the genes responsible for the desaturation as well as their probable origin. We used gene knockout and yeast heterologous expression approaches to identify two putative genes, retrieved from a previous transcriptomic analysis, as sterol C-22 desaturases. Furthermore, we demonstrate using bioinformatics and evolutionary analyses that both genes encode a novel type of sterol C-22 desaturase that belongs to the large fatty acid hydroxylase/desaturase superfamily and the genes originated by genetic duplication prior to functional diversification. These results stress the widespread existence of nonhomologous isofunctional enzymes among different lineages of the tree of life as well as the suitability for the use of T. thermophila as a valuable model to investigate the evolutionary process of large enzyme families.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Both authors contributed equally to this work.
ISSN:	0021-9258 1083-351X
DOI:	10.1016/j.jbc.2022.102397