pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose
Abstract
Yarrowia lipolytica has been used to produce both citric acid and lipid-based bioproducts at high titers. In this study, we found that pH differentially affects citric acid and lipid production in Y. lipolytica W29, with citric acid production enhanced at more neutral pH’s and lipid production enhanced at more acid pH’s. To determine the mechanism governing this pH-dependent switch between citric acid and lipid production, we profiled gene expression at different pH’s and found that the relative expression of multiple transporters is increased at neutral pH. These results suggest that this pH-dependent switch is mediated at the level of citric acid transport rather than changes in the expression of the enzymes involved in citric acid and lipid metabolism. In further support of this mechanism, thermodynamic calculations suggest that citric acid secretion is more energetically favorable at neutral pH’s, assuming the fully protonated acid is the substrate for secretion. Finally, collectively, these results provide new insights regarding citric acid and lipid production in Y. lipolytica and may offer new strategies for metabolic engineering and process design.
- Authors:
-
- University of Illinois at Urbana-Champaign, IL (United States)
- Publication Date:
- Research Org.:
- Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1991853
- Alternate Identifier(s):
- OSTI ID: 1484862
- Grant/Contract Number:
- SC0018420
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biotechnology
- Additional Journal Information:
- Journal Volume: 290; Journal ID: ISSN 0168-1656
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Yarrowia lipolytica; Citric acid; Oleaginous yeast; Lipids; Transporter; RNAseq; citric acid; oleaginous yeast; lipids; transporter
Citation Formats
Zhang, Shuyan, Jagtap, Sujit Sadashiv, Deewan, Anshu, and Rao, Christopher V. pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose. United States: N. p., 2018.
Web. doi:10.1016/j.jbiotec.2018.10.012.
Zhang, Shuyan, Jagtap, Sujit Sadashiv, Deewan, Anshu, & Rao, Christopher V. pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose. United States. https://doi.org/10.1016/j.jbiotec.2018.10.012
Zhang, Shuyan, Jagtap, Sujit Sadashiv, Deewan, Anshu, and Rao, Christopher V. Mon .
"pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose". United States. https://doi.org/10.1016/j.jbiotec.2018.10.012. https://www.osti.gov/servlets/purl/1991853.
@article{osti_1991853,
title = {pH selectively regulates citric acid and lipid production in Yarrowia lipolytica W29 during nitrogen-limited growth on glucose},
author = {Zhang, Shuyan and Jagtap, Sujit Sadashiv and Deewan, Anshu and Rao, Christopher V.},
abstractNote = {Yarrowia lipolytica has been used to produce both citric acid and lipid-based bioproducts at high titers. In this study, we found that pH differentially affects citric acid and lipid production in Y. lipolytica W29, with citric acid production enhanced at more neutral pH’s and lipid production enhanced at more acid pH’s. To determine the mechanism governing this pH-dependent switch between citric acid and lipid production, we profiled gene expression at different pH’s and found that the relative expression of multiple transporters is increased at neutral pH. These results suggest that this pH-dependent switch is mediated at the level of citric acid transport rather than changes in the expression of the enzymes involved in citric acid and lipid metabolism. In further support of this mechanism, thermodynamic calculations suggest that citric acid secretion is more energetically favorable at neutral pH’s, assuming the fully protonated acid is the substrate for secretion. Finally, collectively, these results provide new insights regarding citric acid and lipid production in Y. lipolytica and may offer new strategies for metabolic engineering and process design.},
doi = {10.1016/j.jbiotec.2018.10.012},
journal = {Journal of Biotechnology},
number = ,
volume = 290,
place = {United States},
year = {Mon Nov 26 00:00:00 EST 2018},
month = {Mon Nov 26 00:00:00 EST 2018}
}
Web of Science
Works referenced in this record:
Differential expression analysis for sequence count data
journal, October 2010
- Anders, Simon; Huber, Wolfgang
- Genome Biology, Vol. 11, Issue 10
HTSeq--a Python framework to work with high-throughput sequencing data
journal, September 2014
- Anders, S.; Pyl, P. T.; Huber, W.
- Bioinformatics, Vol. 31, Issue 2
Physiology and genetics of the dimorphic fungus Yarrowia lipolytica
journal, April 1997
- Barth, Gerold; Gaillardin, Claude
- FEMS Microbiology Reviews, Vol. 19, Issue 4, p. 219-237
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
Trimmomatic: a flexible trimmer for Illumina sequence data
journal, April 2014
- Bolger, Anthony M.; Lohse, Marc; Usadel, Bjoern
- Bioinformatics, Vol. 30, Issue 15
Thermodynamic boundary conditions suggest that a passive transport step suffices for citrate excretion in Aspergillus and Penicillium
journal, March 2006
- Burgstaller, Wolfgang
- Microbiology, Vol. 152, Issue 3
Genome evolution in yeasts
journal, July 2004
- Dujon, Bernard; Sherman, David; Fischer, Gilles
- Nature, Vol. 430, Issue 6995
Metabolic Flexibility of Yarrowia lipolytica Growing on Glycerol
journal, January 2017
- Egermeier, Michael; Russmayer, Hannes; Sauer, Michael
- Frontiers in Microbiology, Vol. 8
Predicting Subcellular Localization of Proteins Based on their N-terminal Amino Acid Sequence
journal, July 2000
- Emanuelsson, Olof; Nielsen, Henrik; Brunak, Søren
- Journal of Molecular Biology, Vol. 300, Issue 4
Using GOstats to test gene lists for GO term association
journal, November 2006
- Falcon, S.; Gentleman, R.
- Bioinformatics, Vol. 23, Issue 2
Organic Acid Production by the Yeast Yarrowia lipolytica: A Review of Prospects
journal, September 2005
- Finogenova, T. V.; Morgunov, I. G.; Kamzolova, S. V.
- Applied Biochemistry and Microbiology, Vol. 41, Issue 5
A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues
journal, May 1957
- Folch, Jordi; Lees, M.; Stanley, G. H. Sloane
- Journal of Biological Chemistry, Vol. 226, Issue 1
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions
journal, January 2013
- Kim, Daehwan; Pertea, Geo; Trapnell, Cole
- Genome Biology, Vol. 14, Issue 4
Yarrowia lipolytica as a biotechnological chassis to produce usual and unusual fatty acids
journal, January 2016
- Ledesma-Amaro, Rodrigo; Nicaud, Jean-Marc
- Progress in Lipid Research, Vol. 61
Biotechnological applications of Yarrowia lipolytica: Past, present and future
journal, December 2015
- Liu, Hu-Hu; Ji, Xiao-Jun; Huang, He
- Biotechnology Advances, Vol. 33, Issue 8
Biotechnological production of citric acid
journal, January 2010
- Max, Belén; Salgado, José Manuel; Rodríguez, Noelia
- Brazilian Journal of Microbiology, Vol. 41, Issue 4
The ATP/Substrate Stoichiometry of the ATP-binding Cassette (ABC) Transporter OpuA
journal, May 2003
- Patzlaff, Jason S.; van der Heide, Tiemen; Poolman, Bert
- Journal of Biological Chemistry, Vol. 278, Issue 32
Regulation of lipid accumulation in oleaginous micro-organisms
journal, November 2002
- Ratledge, C.
- Biochemical Society Transactions, Vol. 30, Issue 6, p. 1047-1050
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
journal, November 2009
- Robinson, M. D.; McCarthy, D. J.; Smyth, G. K.
- Bioinformatics, Vol. 26, Issue 1
Overview of citric acid production from Aspergillus niger
journal, April 2015
- Show, Pau Loke; Oladele, Kehinde Opeyemi; Siew, Qi Yan
- Frontiers in Life Science, Vol. 8, Issue 3
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
journal, September 2005
- Subramanian, A.; Tamayo, P.; Mootha, V. K.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550
Impacts of environmental conditions on product formation and morphology of Yarrowia lipolytica
journal, March 2018
- Timoumi, Asma; Guillouet, Stéphane E.; Molina-Jouve, Carole
- Applied Microbiology and Biotechnology, Vol. 102, Issue 9
A comparative study on glycerol metabolism to erythritol and citric acid in Yarrowia lipolytica yeast cells
journal, August 2014
- Tomaszewska, Ludwika; Rakicka, Magdalena; Rymowicz, Waldemar
- FEMS Yeast Research, Vol. 14, Issue 6
Microbial export of lactic and 3-hydroxypropanoic acid: implications for industrial fermentation processes
journal, October 2004
- Maris, Antonius J. A. van; Konings, Wil N.; Dijken, Johannes P. van
- Metabolic Engineering, Vol. 6, Issue 4
Enhanced lipid accumulation in the yeast Yarrowia lipolytica by over-expression of ATP:citrate lyase from Mus musculus
journal, December 2014
- Zhang, Huaiyuan; Zhang, Luning; Chen, Haiqin
- Journal of Biotechnology, Vol. 192
Metabolic engineering of Yarrowia lipolytica for industrial applications
journal, December 2015
- Zhu, Quinn; Jackson, Ethel N.
- Current Opinion in Biotechnology, Vol. 36
Works referencing / citing this record:
Corrigendum: Multi-Omics Analysis of Fatty Alcohol Production in Engineered Yeasts Saccharomyces cerevisiae and Yarrowia lipolytica
journal, January 2021
- Dahlin, Jonathan; Holkenbrink, Carina; Marella, Eko Roy
- Frontiers in Genetics, Vol. 11