Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>

ABSTRACT Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeast Yarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a...

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Autores principales:	Kyle R. Pomraning, Erin L. Bredeweg, Scott E. Baker
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	biotechnology carbon metabolism lipid synthesis metabolic regulation nitrogen metabolism yeasts Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e105e01a1b99474dada1f5c82d708257
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spelling	oai:doaj.org-article:e105e01a1b99474dada1f5c82d7082572021-11-15T15:22:03ZRegulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>10.1128/mSphere.00038-172379-5042https://doaj.org/article/e105e01a1b99474dada1f5c82d7082572017-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00038-17https://doaj.org/toc/2379-5042ABSTRACT Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeast Yarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors on lipid metabolism in Y. lipolytica. Deletion of the GATA transcription factor genes gzf3 and gzf2 resulted in nitrogen source-specific growth defects and greater accumulation of lipids when the cells were growing on a simple nitrogen source. Deletion of gzf1, which is most similar to activators of genes repressed by nitrogen catabolite repression in filamentous ascomycetes, did not affect growth on the nitrogen sources tested. We examined gene expression of wild-type and GATA transcription factor mutants on simple and complex nitrogen sources and found that expression of enzymes involved in malate metabolism, beta-oxidation, and ammonia utilization are strongly upregulated on a simple nitrogen source. Deletion of gzf3 results in overexpression of genes with GATAA sites in their promoters, suggesting that it acts as a repressor, while gzf2 is required for expression of ammonia utilization genes but does not grossly affect the transcription level of genes predicted to be controlled by nitrogen catabolite repression. Both GATA transcription factor mutants exhibit decreased expression of genes controlled by carbon catabolite repression via the repressor mig1, including genes for beta-oxidation, highlighting the complex interplay between regulation of carbon, nitrogen, and lipid metabolism. IMPORTANCE Nitrogen source is commonly used to control lipid production in industrial fungi. Here we identified regulators of nitrogen catabolite repression in the oleaginous yeast Y. lipolytica to determine how the nitrogen source regulates lipid metabolism. We show that disruption of both activators and repressors of nitrogen catabolite repression leads to increased lipid accumulation via activation of carbon catabolite repression through an as yet uncharacterized method.Kyle R. PomraningErin L. BredewegScott E. BakerAmerican Society for Microbiologyarticlebiotechnologycarbon metabolismlipid synthesismetabolic regulationnitrogen metabolismyeastsMicrobiologyQR1-502ENmSphere, Vol 2, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	biotechnology carbon metabolism lipid synthesis metabolic regulation nitrogen metabolism yeasts Microbiology QR1-502
spellingShingle	biotechnology carbon metabolism lipid synthesis metabolic regulation nitrogen metabolism yeasts Microbiology QR1-502 Kyle R. Pomraning Erin L. Bredeweg Scott E. Baker Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
description	ABSTRACT Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeast Yarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors on lipid metabolism in Y. lipolytica. Deletion of the GATA transcription factor genes gzf3 and gzf2 resulted in nitrogen source-specific growth defects and greater accumulation of lipids when the cells were growing on a simple nitrogen source. Deletion of gzf1, which is most similar to activators of genes repressed by nitrogen catabolite repression in filamentous ascomycetes, did not affect growth on the nitrogen sources tested. We examined gene expression of wild-type and GATA transcription factor mutants on simple and complex nitrogen sources and found that expression of enzymes involved in malate metabolism, beta-oxidation, and ammonia utilization are strongly upregulated on a simple nitrogen source. Deletion of gzf3 results in overexpression of genes with GATAA sites in their promoters, suggesting that it acts as a repressor, while gzf2 is required for expression of ammonia utilization genes but does not grossly affect the transcription level of genes predicted to be controlled by nitrogen catabolite repression. Both GATA transcription factor mutants exhibit decreased expression of genes controlled by carbon catabolite repression via the repressor mig1, including genes for beta-oxidation, highlighting the complex interplay between regulation of carbon, nitrogen, and lipid metabolism. IMPORTANCE Nitrogen source is commonly used to control lipid production in industrial fungi. Here we identified regulators of nitrogen catabolite repression in the oleaginous yeast Y. lipolytica to determine how the nitrogen source regulates lipid metabolism. We show that disruption of both activators and repressors of nitrogen catabolite repression leads to increased lipid accumulation via activation of carbon catabolite repression through an as yet uncharacterized method.
format	article
author	Kyle R. Pomraning Erin L. Bredeweg Scott E. Baker
author_facet	Kyle R. Pomraning Erin L. Bredeweg Scott E. Baker
author_sort	Kyle R. Pomraning
title	Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
title_short	Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
title_full	Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
title_fullStr	Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
title_full_unstemmed	Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>
title_sort	regulation of nitrogen metabolism by gata zinc finger transcription factors in <named-content content-type="genus-species">yarrowia lipolytica</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/e105e01a1b99474dada1f5c82d708257
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Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in <named-content content-type="genus-species">Yarrowia lipolytica</named-content>

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