DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Oleaginicity of the yeast strain Saccharomyces cerevisiae D5A

Abstract

Here, the model yeast, Saccharomyces cerevisiae, is not known to be oleaginous. However, an industrial wild-type strain, D5A, was shown to accumulate over 20% storage lipids from glucose when growth is nitrogen-limited compared to no more than 7% lipid accumulation without nitrogen stress. To elucidate the mechanisms of S. cerevisiae D5A oleaginicity, we compared physiological and metabolic changes; as well as the transcriptional profiles of the oleaginous industrial strain, D5A, and a non-oleaginous laboratory strain, BY4741, under normal and nitrogen-limited conditions using analytic techniques and next-generation sequencing-based RNA-Seq transcriptomics. Transcriptional levels for genes associated with fatty acid biosynthesis, nitrogen metabolism, amino acid catabolism, as well as the pentose phosphate pathway and ethanol oxidation in central carbon (C) metabolism, were up-regulated in D5A during nitrogen deprivation. Despite increased carbon flux to lipids, most gene-encoding enzymes involved in triacylglycerol (TAG) assembly were expressed at similar levels regardless of the varying nitrogen concentrations in the growth media and strain backgrounds. Phospholipid turnover also contributed to TAG accumulation through increased precursor production with the down-regulation of subsequent phospholipid synthesis steps. Our results also demonstrated that nitrogen assimilation via the glutamate-glutamine pathway and amino acid metabolism, as well as the fluxes of carbon and reductantsmore » from central C metabolism, are integral to the general oleaginicity of D5A, which resulted in the enhanced lipid storage during nitrogen deprivation. This work demonstrated the disequilibrium and rebalance of carbon and nitrogen contribution to the accumulation of lipids in the oleaginous yeast S. cerevisiae D5A. Rather than TAG assembly from acyl groups, the major switches for the enhanced lipid accumulation of D5A (i.e., fatty acid biosynthesis) are the increases of cytosolic pools of acetyl-CoA and NADPH, as well as alternative nitrogen assimilation.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
National Renewable Energy Laboratory (NREL), Golden, CO (United States)
Sponsoring Org.:
USDOE Office of Energy Efficiency and Renewable Energy (EERE), Sustainable Transportation Office. Bioenergy Technologies Office
OSTI Identifier:
1618737
Alternate Identifier(s):
OSTI ID: 1476705
Report Number(s):
NREL/JA-5100-71803
Journal ID: ISSN 1754-6834; 258; PII: 1256
Grant/Contract Number:  
AC36-08GO28308; 2018ACA149
Resource Type:
Published Article
Journal Name:
Biotechnology for Biofuels
Additional Journal Information:
Journal Name: Biotechnology for Biofuels Journal Volume: 11 Journal Issue: 1; Journal ID: ISSN 1754-6834
Publisher:
Springer Science + Business Media
Country of Publication:
Netherlands
Language:
English
Subject:
09 BIOMASS FUELS; oleaginous yeast; Saccharomyces cerevisiae; transcriptomics; RNA-Seq; lipid accumulation; triacylglycerol (TAG); nitrogen assimilation

Citation Formats

He, Qiaoning, Yang, Yongfu, Yang, Shihui, Donohoe, Bryon S., Van Wychen, Stefanie, Zhang, Min, Himmel, Michael E., and Knoshaug, Eric P. Oleaginicity of the yeast strain Saccharomyces cerevisiae D5A. Netherlands: N. p., 2018. Web. doi:10.1186/s13068-018-1256-z.
He, Qiaoning, Yang, Yongfu, Yang, Shihui, Donohoe, Bryon S., Van Wychen, Stefanie, Zhang, Min, Himmel, Michael E., & Knoshaug, Eric P. Oleaginicity of the yeast strain Saccharomyces cerevisiae D5A. Netherlands. https://doi.org/10.1186/s13068-018-1256-z
He, Qiaoning, Yang, Yongfu, Yang, Shihui, Donohoe, Bryon S., Van Wychen, Stefanie, Zhang, Min, Himmel, Michael E., and Knoshaug, Eric P. Mon . "Oleaginicity of the yeast strain Saccharomyces cerevisiae D5A". Netherlands. https://doi.org/10.1186/s13068-018-1256-z.
@article{osti_1618737,
title = {Oleaginicity of the yeast strain Saccharomyces cerevisiae D5A},
author = {He, Qiaoning and Yang, Yongfu and Yang, Shihui and Donohoe, Bryon S. and Van Wychen, Stefanie and Zhang, Min and Himmel, Michael E. and Knoshaug, Eric P.},
abstractNote = {Here, the model yeast, Saccharomyces cerevisiae, is not known to be oleaginous. However, an industrial wild-type strain, D5A, was shown to accumulate over 20% storage lipids from glucose when growth is nitrogen-limited compared to no more than 7% lipid accumulation without nitrogen stress. To elucidate the mechanisms of S. cerevisiae D5A oleaginicity, we compared physiological and metabolic changes; as well as the transcriptional profiles of the oleaginous industrial strain, D5A, and a non-oleaginous laboratory strain, BY4741, under normal and nitrogen-limited conditions using analytic techniques and next-generation sequencing-based RNA-Seq transcriptomics. Transcriptional levels for genes associated with fatty acid biosynthesis, nitrogen metabolism, amino acid catabolism, as well as the pentose phosphate pathway and ethanol oxidation in central carbon (C) metabolism, were up-regulated in D5A during nitrogen deprivation. Despite increased carbon flux to lipids, most gene-encoding enzymes involved in triacylglycerol (TAG) assembly were expressed at similar levels regardless of the varying nitrogen concentrations in the growth media and strain backgrounds. Phospholipid turnover also contributed to TAG accumulation through increased precursor production with the down-regulation of subsequent phospholipid synthesis steps. Our results also demonstrated that nitrogen assimilation via the glutamate-glutamine pathway and amino acid metabolism, as well as the fluxes of carbon and reductants from central C metabolism, are integral to the general oleaginicity of D5A, which resulted in the enhanced lipid storage during nitrogen deprivation. This work demonstrated the disequilibrium and rebalance of carbon and nitrogen contribution to the accumulation of lipids in the oleaginous yeast S. cerevisiae D5A. Rather than TAG assembly from acyl groups, the major switches for the enhanced lipid accumulation of D5A (i.e., fatty acid biosynthesis) are the increases of cytosolic pools of acetyl-CoA and NADPH, as well as alternative nitrogen assimilation.},
doi = {10.1186/s13068-018-1256-z},
journal = {Biotechnology for Biofuels},
number = 1,
volume = 11,
place = {Netherlands},
year = {Mon Sep 24 00:00:00 EDT 2018},
month = {Mon Sep 24 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1186/s13068-018-1256-z

Citation Metrics:
Cited by: 20 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Microbial lipid-based lignocellulosic biorefinery: feasibility and challenges
journal, January 2015


Biodiesel production from oleaginous microorganisms
journal, January 2009


Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae
journal, February 2012


Fatty Acid-Derived Biofuels and Chemicals Production in Saccharomyces cerevisiae
journal, September 2014

  • Zhou, Yongjin J.; Buijs, Nicolaas A.; Siewers, Verena
  • Frontiers in Bioengineering and Biotechnology, Vol. 2
  • DOI: 10.3389/fbioe.2014.00032

Advances in ethanol production
journal, June 2011

  • Geddes, Claudia C.; Nieves, Ismael U.; Ingram, Lonnie O.
  • Current Opinion in Biotechnology, Vol. 22, Issue 3
  • DOI: 10.1016/j.copbio.2011.04.012

TCA cycle-independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae
journal, November 2010

  • Lee, Yong Joo; Jang, Jin Won; Kim, Kyung Jin
  • Yeast, Vol. 28, Issue 2
  • DOI: 10.1002/yea.1828

Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica
journal, March 2016

  • Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.
  • npj Systems Biology and Applications, Vol. 2, Issue 1
  • DOI: 10.1038/npjsba.2016.5

The alcohol dehydrogenases of Saccharomyces cerevisiae: a comprehensive review
journal, November 2008


Comparative proteomic analysis of Rhodosporidium toruloides during lipid accumulation
journal, October 2009

  • Liu, Hongwei; Zhao, Xin; Wang, Fangjun
  • Yeast, Vol. 26, Issue 10
  • DOI: 10.1002/yea.1706

Engineering the fatty acid metabolic pathway in Saccharomyces cerevisiae for advanced biofuel production
journal, December 2015


Yarrowia lipolytica as a model for bio-oil production
journal, November 2009

  • Beopoulos, Athanasios; Cescut, Julien; Haddouche, Ramdane
  • Progress in Lipid Research, Vol. 48, Issue 6, p. 375-387
  • DOI: 10.1016/j.plipres.2009.08.005

DGA1 (diacylglycerol acyltransferase gene) overexpression and leucine biosynthesis significantly increase lipid accumulation in the Δsnf2 disruptant of Saccharomyces cerevisiae
journal, November 2007

  • Kamisaka, Yasushi; Tomita, Nao; Kimura, Kazuyoshi
  • Biochemical Journal, Vol. 408, Issue 1, p. 61-68
  • DOI: 10.1042/BJ20070449

Glutamate synthase levels in Neurospora crassa mutants altered with respect to nitrogen metabolism.
journal, February 1981

  • Dunn-Coleman, N. S.; Robey, E. A.; Tomsett, A. B.
  • Molecular and Cellular Biology, Vol. 1, Issue 2
  • DOI: 10.1128/MCB.1.2.158

Transcriptomic and metabolomic profiling of Zymomonas mobilis during aerobic and anaerobic fermentations
journal, January 2009

  • Yang, Shihui; Tschaplinski, Timothy J.; Engle, Nancy L.
  • BMC Genomics, Vol. 10, Issue 1
  • DOI: 10.1186/1471-2164-10-34

Combined algal processing: A novel integrated biorefinery process to produce algal biofuels and bioproducts
journal, November 2016


Glycerol stress in S accharomyces cerevisiae : Cellular responses and evolved adaptations : Glycerol Stress in
journal, January 2017

  • Mattenberger, Florian; Sabater-Muñoz, Beatriz; Hallsworth, John E.
  • Environmental Microbiology, Vol. 19, Issue 3
  • DOI: 10.1111/1462-2920.13603

Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae
journal, February 2018

  • Zhang, Weiping; Du, Guocheng; Zhou, Jingwen
  • Microbiology and Molecular Biology Reviews, Vol. 82, Issue 1
  • DOI: 10.1128/MMBR.00040-17

Lipid accumulation from glucose and xylose in an engineered, naturally oleaginous strain of Saccharomyces cerevisiae
journal, June 2018

  • Knoshaug, Eric P.; Van Wychen, Stefanie; Singh, Arjun
  • Biofuel Research Journal, Vol. 5, Issue 2
  • DOI: 10.18331/BRJ2018.5.2.3

Fatty acid synthesis and elongation in yeast
journal, March 2007

  • Tehlivets, Oksana; Scheuringer, Kim; Kohlwein, Sepp D.
  • Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1771, Issue 3, p. 255-270
  • DOI: 10.1016/j.bbalip.2006.07.004

Integrated analysis of transcriptome and lipid profiling reveals the co-influences of inositol–choline and Snf1 in controlling lipid biosynthesis in yeast
journal, May 2012

  • Chumnanpuen, Pramote; Zhang, Jie; Nookaew, Intawat
  • Molecular Genetics and Genomics, Vol. 287, Issue 7
  • DOI: 10.1007/s00438-012-0697-5

The Techno-Economic Basis for Coproduct Manufacturing To Enable Hydrocarbon Fuel Production from Lignocellulosic Biomass
journal, May 2016


Engineering lipid overproduction in the oleaginous yeast Yarrowia lipolytica
journal, May 2015


Lipids of oleaginous yeasts. Part I: Biochemistry of single cell oil production
journal, June 2011

  • Papanikolaou, Seraphim; Aggelis, George
  • European Journal of Lipid Science and Technology, Vol. 113, Issue 8
  • DOI: 10.1002/ejlt.201100014

The oxidative pentose phosphate pathway is the primary source of NADPH for lipid overproduction from glucose in Yarrowia lipolytica
journal, July 2015


Overproduction and secretion of free fatty acids through disrupted neutral lipid recycle in Saccharomyces cerevisiae
journal, March 2015


The novel zinc cluster regulator Tog1 plays important roles in oleate utilization and oxidative stress response in Saccharomyces cerevisiae
journal, August 2014

  • Thepnok, Piyasuda; Ratanakhanokchai, Khanok; Soontorngun, Nitnipa
  • Biochemical and Biophysical Research Communications, Vol. 450, Issue 4
  • DOI: 10.1016/j.bbrc.2014.06.128

Nitrogen-Sparing Mechanisms in Chlamydomonas Affect the Transcriptome, the Proteome, and Photosynthetic Metabolism
journal, April 2014

  • Schmollinger, Stefan; Mühlhaus, Timo; Boyle, Nanette R.
  • The Plant Cell, Vol. 26, Issue 4
  • DOI: 10.1105/tpc.113.122523

Profiling of Cytosolic and Peroxisomal Acetyl-CoA Metabolism in Saccharomyces cerevisiae
journal, August 2012


Nitrogen regulation in Saccharomyces cerevisiae
journal, May 2002


The proteome analysis of oleaginous yeast Lipomyces starkeyi: Comparative proteomic analysis of Lipomyces starkeyi
journal, October 2010


Not just a circle: flux modes in the plant TCA cycle
journal, August 2010


Systems-Level Analysis of Nitrogen Starvation-Induced Modifications of Carbon Metabolism in a Chlamydomonas reinhardtii Starchless Mutant
journal, November 2013


Regulation of lipid accumulation in oleaginous micro-organisms
journal, November 2002

  • Ratledge, C.
  • Biochemical Society Transactions, Vol. 30, Issue 6, p. 1047-1050
  • DOI: 10.1042/bst0301047

Metabolic engineering of Saccharomyces cerevisiae to produce a reduced viscosity oil from lignocellulose
journal, March 2017

  • Tran, Tam N. T.; Breuer, Rebecca J.; Avanasi Narasimhan, Ragothaman
  • Biotechnology for Biofuels, Vol. 10, Issue 1
  • DOI: 10.1186/s13068-017-0751-y

Lipid production in Nannochloropsis gaditana is doubled by decreasing expression of a single transcriptional regulator
journal, June 2017

  • Ajjawi, Imad; Verruto, John; Aqui, Moena
  • Nature Biotechnology, Vol. 35, Issue 7
  • DOI: 10.1038/nbt.3865

Lipid recovery from wet oleaginous microbial biomass for biofuel production: A critical review
journal, September 2016


Systems biology of lipid metabolism: From yeast to human
journal, October 2009


Improvement of Ethanol Yield from Glycerol via Conversion of Pyruvate to Ethanol in Metabolically Engineered Saccharomyces cerevisiae
journal, December 2011

  • Yu, Kyung Ok; Jung, Ju; Ramzi, Ahmad Bazli
  • Applied Biochemistry and Biotechnology, Vol. 166, Issue 4
  • DOI: 10.1007/s12010-011-9475-9

Manipulation of culture conditions alters lipid content and fatty acid profiles of a wide variety of known and new oleaginous yeast species
journal, September 2013


Butanol Tolerance in a Selection of Microorganisms
journal, December 2008


Transcriptomic Analyses during the Transition from Biomass Production to Lipid Accumulation in the Oleaginous Yeast Yarrowia lipolytica
journal, November 2011


Enhanced amino acid utilization sustains growth of cells lacking Snf1/AMPK
journal, July 2015

  • Nicastro, Raffaele; Tripodi, Farida; Guzzi, Cinzia
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1853, Issue 7
  • DOI: 10.1016/j.bbamcr.2015.03.014

Remodeling of intermediate metabolism in the diatom Phaeodactylum tricornutum under nitrogen stress
journal, December 2014

  • Levitan, Orly; Dinamarca, Jorge; Zelzion, Ehud
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 2
  • DOI: 10.1073/pnas.1419818112

Combined “de novo” and “ex novo” lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis
journal, June 2017


Fatty alcohol production in Lipomyces starkeyi and Yarrowia lipolytica
journal, October 2016


Engineering Rhodosporidium toruloides for increased lipid production : Engineering
journal, November 2015

  • Zhang, Shuyan; Skerker, Jeffrey M.; Rutter, Charles D.
  • Biotechnology and Bioengineering, Vol. 113, Issue 5
  • DOI: 10.1002/bit.25864

Multi-omics analysis reveals regulators of the response to nitrogen limitation in Yarrowia lipolytica
journal, February 2016


Saccharomyces cerevisiae Mutants Resistant to Catabolite Repression: Use in Cheese Whey Hydrolysate Fermentation
journal, January 1982


Overexpression of OLE1 enhances stress tolerance and constitutively activates the MAPK HOG pathway in Saccharomyces cerevisiae : Enhanced Stress Tolerance by
journal, November 2016

  • Nasution, Olviyani; Lee, Young Mi; Kim, Eunjung
  • Biotechnology and Bioengineering, Vol. 114, Issue 3
  • DOI: 10.1002/bit.26093

Metabolic engineering of yeast for production of fuels and chemicals
journal, June 2013

  • Nielsen, Jens; Larsson, Christer; van Maris, Antonius
  • Current Opinion in Biotechnology, Vol. 24, Issue 3
  • DOI: 10.1016/j.copbio.2013.03.023

Oily yeasts as oleaginous cell factories
journal, April 2011

  • Ageitos, Jose Manuel; Vallejo, Juan Andres; Veiga-Crespo, Patricia
  • Applied Microbiology and Biotechnology, Vol. 90, Issue 4
  • DOI: 10.1007/s00253-011-3200-z

Choreography of Transcriptomes and Lipidomes of Nannochloropsis Reveals the Mechanisms of Oil Synthesis in Microalgae
journal, April 2014


Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals
journal, January 2014


Advancing oleaginous microorganisms to produce lipid via metabolic engineering technology
journal, October 2013


Overproduction of fatty acids in engineered Saccharomyces cerevisiae
journal, April 2014

  • Li, Xiaowei; Guo, Daoyi; Cheng, Yongbo
  • Biotechnology and Bioengineering, Vol. 111, Issue 9, p. 1841-1852
  • DOI: 10.1002/bit.25239

The Response of Diatom Central Carbon Metabolism to Nitrogen Starvation Is Different from That of Green Algae and Higher Plants
journal, November 2011

  • Hockin, Nicola Louise; Mock, Thomas; Mulholland, Francis
  • Plant Physiology, Vol. 158, Issue 1
  • DOI: 10.1104/pp.111.184333

Genome-wide location analysis reveals an important overlap between the targets of the yeast transcriptional regulators Rds2 and Adr1
journal, July 2012

  • Soontorngun, Nitnipa; Baramee, Sirilak; Tangsombatvichit, Chalinee
  • Biochemical and Biophysical Research Communications, Vol. 423, Issue 4
  • DOI: 10.1016/j.bbrc.2012.05.151

A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides
journal, January 2012

  • Zhu, Zhiwei; Zhang, Sufang; Liu, Hongwei
  • Nature Communications, Vol. 3, Issue 1
  • DOI: 10.1038/ncomms2112

Oleaginous yeasts for biodiesel: Current and future trends in biology and production
journal, November 2014


Engineering increased triacylglycerol accumulation in Saccharomyces cerevisiae using a modified type 1 plant diacylglycerol acyltransferase
journal, December 2014

  • Greer, Michael S.; Truksa, Martin; Deng, Wei
  • Applied Microbiology and Biotechnology, Vol. 99, Issue 5
  • DOI: 10.1007/s00253-014-6284-4

Works referencing / citing this record:

Insights into the Metabolism of Oleaginous Rhodococcus spp.
journal, July 2019

  • Alvarez, Héctor M.; Herrero, O. Marisa; Silva, Roxana A.
  • Applied and Environmental Microbiology, Vol. 85, Issue 18
  • DOI: 10.1128/aem.00498-19