1. A novel Tetrahymena thermophila sterol C-22 desaturase belongs to the fatty acid hydroxylase/desaturase superfamily.
- Author
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Sanchez Granel ML, Siburu NG, Fricska A, Maldonado LL, Gargiulo LB, Nudel CB, Uttaro AD, and Nusblat AD
- Subjects
- Fatty Acid Desaturases genetics, Fatty Acid Desaturases metabolism, Saccharomyces cerevisiae, Sterols metabolism, Phylogeny, Stearoyl-CoA Desaturase chemistry, Stearoyl-CoA Desaturase classification, Stearoyl-CoA Desaturase genetics, Tetrahymena thermophila enzymology, Protozoan Proteins chemistry, Protozoan Proteins classification, Protozoan Proteins genetics
- Abstract
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., Competing Interests: Conflict of interest A. D. N., A. D. U., and C. B. N. are members of the Consejo Nacional de Investigaciones Científicas y Técnicas. The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2022
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