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Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous

Xanthophyllomyces dendrorhous is a basidiomycete yeast that synthesizes carotenoids, mainly astaxanthin, which are of great commercial interest. Currently, there are many unknown aspects related to regulatory mechanisms on the synthesis of carotenoids in this yeast. Our recent studies showed that ch...

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Autores principales: Gutiérrez, María Soledad, Campusano, Sebastián, González, Ana María, Gómez, Melissa, Barahona, Salvador, Sepúlveda, Dionisia, Espenshade, Peter J., Fernández-Lobato, María, Baeza, Marcelo, Cifuentes, Víctor, Alcaíno, Jennifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449425/
https://www.ncbi.nlm.nih.gov/pubmed/30984134
http://dx.doi.org/10.3389/fmicb.2019.00586
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author Gutiérrez, María Soledad
Campusano, Sebastián
González, Ana María
Gómez, Melissa
Barahona, Salvador
Sepúlveda, Dionisia
Espenshade, Peter J.
Fernández-Lobato, María
Baeza, Marcelo
Cifuentes, Víctor
Alcaíno, Jennifer
author_facet Gutiérrez, María Soledad
Campusano, Sebastián
González, Ana María
Gómez, Melissa
Barahona, Salvador
Sepúlveda, Dionisia
Espenshade, Peter J.
Fernández-Lobato, María
Baeza, Marcelo
Cifuentes, Víctor
Alcaíno, Jennifer
author_sort Gutiérrez, María Soledad
collection PubMed
description Xanthophyllomyces dendrorhous is a basidiomycete yeast that synthesizes carotenoids, mainly astaxanthin, which are of great commercial interest. Currently, there are many unknown aspects related to regulatory mechanisms on the synthesis of carotenoids in this yeast. Our recent studies showed that changes in sterol levels and composition resulted in upregulation of genes in the mevalonate pathway required for the synthesis of carotenoid precursors, leading to increased production of these pigments. Sterol Regulatory Element-Binding Proteins (SREBP), called Sre1 in yeast, are conserved transcriptional regulators of sterol homeostasis and other cellular processes. Given the results linking sterols and carotenoids, we investigated the role of SREBP in sterol and carotenoid synthesis in X. dendrorhous. In this study, we present the identification and functional characterization of the X. dendrorhous SRE1 gene, which encodes the transcription factor Sre1. The deduced protein has the characteristic features of SREBP/Sre1 and binds to consensus DNA sequences in vitro. RNA-seq analysis and chromatin-immunoprecipitation experiments showed that genes of the mevalonate pathway and ergosterol biosynthesis are directly regulated by Sre1. The sre1(-) mutation reduced sterol and carotenoid production in X. dendrorhous, and expression of the Sre1 N-terminal domain (Sre1N) increased carotenoid production more than twofold compared to wild-type. Overall, our results indicate that in X. dendrorhous transcriptional regulation of genes in the mevalonate pathway control production of the isoprenoid derivatives, carotenoids and sterol. Our results provide new insights into the conserved regulatory functions of SREBP/Sre1 and identify pointing to the SREBP pathway as a potential target to enhance carotenoid production in X. dendrorhous.
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spelling pubmed-64494252019-04-12 Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous Gutiérrez, María Soledad Campusano, Sebastián González, Ana María Gómez, Melissa Barahona, Salvador Sepúlveda, Dionisia Espenshade, Peter J. Fernández-Lobato, María Baeza, Marcelo Cifuentes, Víctor Alcaíno, Jennifer Front Microbiol Microbiology Xanthophyllomyces dendrorhous is a basidiomycete yeast that synthesizes carotenoids, mainly astaxanthin, which are of great commercial interest. Currently, there are many unknown aspects related to regulatory mechanisms on the synthesis of carotenoids in this yeast. Our recent studies showed that changes in sterol levels and composition resulted in upregulation of genes in the mevalonate pathway required for the synthesis of carotenoid precursors, leading to increased production of these pigments. Sterol Regulatory Element-Binding Proteins (SREBP), called Sre1 in yeast, are conserved transcriptional regulators of sterol homeostasis and other cellular processes. Given the results linking sterols and carotenoids, we investigated the role of SREBP in sterol and carotenoid synthesis in X. dendrorhous. In this study, we present the identification and functional characterization of the X. dendrorhous SRE1 gene, which encodes the transcription factor Sre1. The deduced protein has the characteristic features of SREBP/Sre1 and binds to consensus DNA sequences in vitro. RNA-seq analysis and chromatin-immunoprecipitation experiments showed that genes of the mevalonate pathway and ergosterol biosynthesis are directly regulated by Sre1. The sre1(-) mutation reduced sterol and carotenoid production in X. dendrorhous, and expression of the Sre1 N-terminal domain (Sre1N) increased carotenoid production more than twofold compared to wild-type. Overall, our results indicate that in X. dendrorhous transcriptional regulation of genes in the mevalonate pathway control production of the isoprenoid derivatives, carotenoids and sterol. Our results provide new insights into the conserved regulatory functions of SREBP/Sre1 and identify pointing to the SREBP pathway as a potential target to enhance carotenoid production in X. dendrorhous. Frontiers Media S.A. 2019-03-29 /pmc/articles/PMC6449425/ /pubmed/30984134 http://dx.doi.org/10.3389/fmicb.2019.00586 Text en Copyright © 2019 Gutiérrez, Campusano, González, Gómez, Barahona, Sepúlveda, Espenshade, Fernández-Lobato, Baeza, Cifuentes and Alcaíno. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Gutiérrez, María Soledad
Campusano, Sebastián
González, Ana María
Gómez, Melissa
Barahona, Salvador
Sepúlveda, Dionisia
Espenshade, Peter J.
Fernández-Lobato, María
Baeza, Marcelo
Cifuentes, Víctor
Alcaíno, Jennifer
Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title_full Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title_fullStr Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title_full_unstemmed Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title_short Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous
title_sort sterol regulatory element-binding protein (sre1) promotes the synthesis of carotenoids and sterols in xanthophyllomyces dendrorhous
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449425/
https://www.ncbi.nlm.nih.gov/pubmed/30984134
http://dx.doi.org/10.3389/fmicb.2019.00586
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