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Title: Regulation of nitrogen metabolism by GATA zinc finger transcription factors in Yarrowia lipolytica

Abstract

Here, 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 amore » 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.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [2]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Carnegie Mellon Univ., Pittsburgh, PA (United States)
Publication Date:
Research Org.:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1366736
Grant/Contract Number:  
SC0008744
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
mSphere
Additional Journal Information:
Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 2379-5042
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biotechnology; carbon metabolism; lipid synthesis; metabolic regulation; nitrogen metabolism; yeasts; Yarrowia lipolytica; nitrogen catabolite repression; carbon catabolite repression; zinc finger; transcription factor; GATA transcription factor; GATA; nitrogen; gene regulation; oleaginous yeast; lipid metabolism

Citation Formats

Pomraning, Kyle R., Bredeweg, Erin L., Baker, Scott E., and Mitchell, Aaron P. Regulation of nitrogen metabolism by GATA zinc finger transcription factors in Yarrowia lipolytica. United States: N. p., 2017. Web. doi:10.1128/mSphere.00038-17.
Pomraning, Kyle R., Bredeweg, Erin L., Baker, Scott E., & Mitchell, Aaron P. Regulation of nitrogen metabolism by GATA zinc finger transcription factors in Yarrowia lipolytica. United States. doi:10.1128/mSphere.00038-17.
Pomraning, Kyle R., Bredeweg, Erin L., Baker, Scott E., and Mitchell, Aaron P. Wed . "Regulation of nitrogen metabolism by GATA zinc finger transcription factors in Yarrowia lipolytica". United States. doi:10.1128/mSphere.00038-17. https://www.osti.gov/servlets/purl/1366736.
@article{osti_1366736,
title = {Regulation of nitrogen metabolism by GATA zinc finger transcription factors in Yarrowia lipolytica},
author = {Pomraning, Kyle R. and Bredeweg, Erin L. and Baker, Scott E. and Mitchell, Aaron P.},
abstractNote = {Here, 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.},
doi = {10.1128/mSphere.00038-17},
journal = {mSphere},
number = 1,
volume = 2,
place = {United States},
year = {Wed Feb 15 00:00:00 EST 2017},
month = {Wed Feb 15 00:00:00 EST 2017}
}

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