skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses

Abstract

Microalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems-level understanding of their metabolism, which can be fundamentally achieved through large-scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome-scale metabolic model for the widely-studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting for 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat-grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high-resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway-level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, themore » cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth-associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome-scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [3];  [4]
  1. Institute for Systems Biology, Seattle, WA (United States)
  2. Institute for Systems Biology, Seattle, WA (United States); Friedrich-Schiller-Univ. Jena, Jena (Germany)
  3. Institute for Systems Biology, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
  4. Institute for Systems Biology, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1378660
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
The Plant Journal
Additional Journal Information:
Journal Volume: 84; Journal Issue: 6; Journal ID: ISSN 0960-7412
Publisher:
Society for Experimental Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; metabolic modeling; Chlamydomonas reinhardtii; constraint-based analysis; flux balance analysis; data integration; systems biology; biomass; lipid accumulation; photosynthesis

Citation Formats

Imam, Saheed, Schäuble, Sascha, Valenzuela, Jacob, Lopez Garcia de Lomana, Adrian, Carter, Warren, Price, Nathan D., and Baliga, Nitin S. A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses. United States: N. p., 2015. Web. doi:10.1111/tpj.13059.
Imam, Saheed, Schäuble, Sascha, Valenzuela, Jacob, Lopez Garcia de Lomana, Adrian, Carter, Warren, Price, Nathan D., & Baliga, Nitin S. A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses. United States. doi:10.1111/tpj.13059.
Imam, Saheed, Schäuble, Sascha, Valenzuela, Jacob, Lopez Garcia de Lomana, Adrian, Carter, Warren, Price, Nathan D., and Baliga, Nitin S. Tue . "A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses". United States. doi:10.1111/tpj.13059. https://www.osti.gov/servlets/purl/1378660.
@article{osti_1378660,
title = {A refined genome-scale reconstruction of Chlamydomonas metabolism provides a platform for systems-level analyses},
author = {Imam, Saheed and Schäuble, Sascha and Valenzuela, Jacob and Lopez Garcia de Lomana, Adrian and Carter, Warren and Price, Nathan D. and Baliga, Nitin S.},
abstractNote = {Microalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems-level understanding of their metabolism, which can be fundamentally achieved through large-scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome-scale metabolic model for the widely-studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting for 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat-grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high-resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway-level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, the cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth-associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome-scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae.},
doi = {10.1111/tpj.13059},
journal = {The Plant Journal},
number = 6,
volume = 84,
place = {United States},
year = {2015},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 14 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Three Acyltransferases and Nitrogen-responsive Regulator Are Implicated in Nitrogen Starvation-induced Triacylglycerol Accumulation in Chlamydomonas
journal, March 2012

  • Boyle, Nanette R.; Page, Mark Dudley; Liu, Bensheng
  • Journal of Biological Chemistry, Vol. 287, Issue 19
  • DOI: 10.1074/jbc.M111.334052

Powering the planet: Chemical challenges in solar energy utilization
journal, October 2006

  • Lewis, N. S.; Nocera, D. G.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 43, p. 15729-15735
  • DOI: 10.1073/pnas.0603395103

Transforming RNA-Seq Data to Improve the Performance of Prognostic Gene Signatures
journal, January 2014


The Pfam Protein Families Database
journal, January 2002


RELATCH: relative optimality in metabolic networks explains robust metabolic and regulatory responses to perturbations
journal, January 2012


The rotary mechanism of ATP synthase
journal, December 2000


The geographical distribution of fossil fuels unused when limiting global warming to 2 °C
journal, January 2015


Microalgal carbon-dioxide-concentrating mechanisms: Chlamydomonas inorganic carbon transporters
journal, June 2007

  • Spalding, M. H.
  • Journal of Experimental Botany, Vol. 59, Issue 7
  • DOI: 10.1093/jxb/erm128

Impact of Oxidative Stress on Ascorbate Biosynthesis in Chlamydomonas via Regulation of the VTC2 Gene Encoding a GDP-l-galactose Phosphorylase
journal, March 2012

  • Urzica, Eugen I.; Adler, Lital N.; Page, M. Dudley
  • Journal of Biological Chemistry, Vol. 287, Issue 17
  • DOI: 10.1074/jbc.M112.341982

Biodiesel from algae: challenges and prospects
journal, June 2010


The chloroplast proteome: a survey from the Chlamydomonas reinhardtii perspective with a focus on distinctive features
journal, April 2011


Large Scale Comparison of Gene Expression Levels by Microarrays and RNAseq Using TCGA Data
journal, August 2013


Accomplishments in genome-scale in silico modeling for industrial and medical biotechnology
journal, December 2009

  • Milne, Caroline B.; Kim, Pan-Jun; Eddy, James A.
  • Biotechnology Journal, Vol. 4, Issue 12
  • DOI: 10.1002/biot.200900234

Substrate inhibition of Chlamydomonas reinhardtii by acetate in heterotrophic culture
journal, January 1994


Locating proteins in the cell using TargetP, SignalP and related tools
journal, April 2007

  • Emanuelsson, Olof; Brunak, Søren; von Heijne, Gunnar
  • Nature Protocols, Vol. 2, Issue 4
  • DOI: 10.1038/nprot.2007.131

Data, information, knowledge and principle: back to metabolism in KEGG
journal, November 2013

  • Kanehisa, Minoru; Goto, Susumu; Sato, Yoko
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1076

Green genes: bioinformatics and systems-biology innovations drive algal biotechnology
journal, December 2014

  • Reijnders, Maarten J. M. F.; van Heck, Ruben G. A.; Lam, Carolyn M. C.
  • Trends in Biotechnology, Vol. 32, Issue 12
  • DOI: 10.1016/j.tibtech.2014.10.003

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function
journal, July 2011

  • Petti, A. A.; Crutchfield, C. A.; Rabinowitz, J. D.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 45
  • DOI: 10.1073/pnas.1101494108

Drought, salt, and temperature stress-induced metabolic rearrangements and regulatory networks
journal, January 2012

  • Krasensky, J.; Jonak, C.
  • Journal of Experimental Botany, Vol. 63, Issue 4
  • DOI: 10.1093/jxb/err460

Identification of Novel Mitochondrial Protein Components of Chlamydomonas reinhardtii . A Proteomic Approach
journal, April 2003

  • van Lis, Robert; Atteia, Ariane; Mendoza-Hernández, Guillermo
  • Plant Physiology, Vol. 132, Issue 1
  • DOI: 10.1104/pp.102.018325

Metabolite Profiling of Chlamydomonas reinhardtii under Nutrient Deprivation
journal, November 2005


A chloroplast pathway for the de novo biosynthesis of triacylglycerol in Chlamydomonas reinhardtii
journal, May 2011


The Geological Record of Ocean Acidification
journal, March 2012


Proteomic analysis of a eukaryotic cilium
journal, July 2005

  • Pazour, Gregory J.; Agrin, Nathan; Leszyk, John
  • The Journal of Cell Biology, Vol. 170, Issue 1
  • DOI: 10.1083/jcb.200504008

Metabolic network reconstruction of Chlamydomonas offers insight into light‐driven algal metabolism
journal, January 2011

  • Chang, Roger L.; Ghamsari, Lila; Manichaikul, Ani
  • Molecular Systems Biology, Vol. 7, Issue 1
  • DOI: 10.1038/msb.2011.52

Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity
journal, August 2013

  • Moulin, Michael; Nguyen, Ginnie T. D. T.; Scaife, Mark A.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 36
  • DOI: 10.1073/pnas.1307741110

The effects of alternate optimal solutions in constraint-based genome-scale metabolic models
journal, October 2003


Carotenoid deficiency triggers autophagy in the model green alga Chlamydomonas reinhardtii
journal, March 2012

  • Pérez-Pérez, María Esther; Couso, Inmaculada; Crespo, José L.
  • Autophagy, Vol. 8, Issue 3
  • DOI: 10.4161/auto.18864

Zeaxanthin Deficiency Enhances the High Light Sensitivity of an Ascorbate-Deficient Mutant of Arabidopsis
journal, August 2003

  • Müller-Moulé, Patricia; Havaux, Michel; Niyogi, Krishna K.
  • Plant Physiology, Vol. 133, Issue 2
  • DOI: 10.1104/pp.103.026252

The Pfam protein families database
journal, January 2004

  • Bateman, Alex; Coin, Lachlan; Durbin, Richard
  • Nucleic Acids Research, Vol. 32, Issue S1, p. D138-D141
  • DOI: 10.1093/nar/gkh121

Network-based prediction of human tissue-specific metabolism
journal, August 2008

  • Shlomi, Tomer; Cabili, Moran N.; Herrgård, Markus J.
  • Nature Biotechnology, Vol. 26, Issue 9
  • DOI: 10.1038/nbt.1487

Remodeling of Membrane Lipids in Iron-starved Chlamydomonas
journal, August 2013

  • Urzica, Eugen I.; Vieler, Astrid; Hong-Hermesdorf, Anne
  • Journal of Biological Chemistry, Vol. 288, Issue 42
  • DOI: 10.1074/jbc.M113.490425

Impact of Anthropogenic CO2 on the CaCO3 System in the Oceans
journal, July 2004


Metabolic acclimation to excess light intensity in Chlamydomonas reinhardtii : High-light metabolomics of
journal, February 2013

  • Davis, Maria C.; Fiehn, Oliver; Durnford, Dion G.
  • Plant, Cell & Environment, Vol. 36, Issue 7
  • DOI: 10.1111/pce.12071

iBsu1103: a new genome-scale metabolic model of Bacillus subtilis based on SEED annotations
journal, January 2009

  • Henry, Christopher S.; Zinner, Jenifer F.; Cohoon, Matthew P.
  • Genome Biology, Vol. 10, Issue 6
  • DOI: 10.1186/gb-2009-10-6-r69

Changes in Transcript Abundance in Chlamydomonas reinhardtii following Nitrogen Deprivation Predict Diversion of Metabolism
journal, October 2010

  • Miller, Rachel; Wu, Guangxi; Deshpande, Rahul R.
  • Plant Physiology, Vol. 154, Issue 4
  • DOI: 10.1104/pp.110.165159

Effect of nitrogen starvation on ammonium assimilation by Chlamydomonas reinhardtii
journal, February 1989


Metabolic modeling of Chlamydomonas reinhardtii: energy requirements for photoautotrophic growth and maintenance
journal, April 2011

  • Kliphuis, Anna M. J.; Klok, Anne J.; Martens, Dirk E.
  • Journal of Applied Phycology, Vol. 24, Issue 2
  • DOI: 10.1007/s10811-011-9674-3

Synthesizing and Salvaging NAD+: Lessons Learned from Chlamydomonas reinhardtii
journal, September 2010


The response of Chlamydomonas reinhardtii to nitrogen deprivation: a systems biology analysis
journal, February 2015

  • Park, Jeong-Jin; Wang, Hongxia; Gargouri, Mahmoud
  • The Plant Journal, Vol. 81, Issue 4
  • DOI: 10.1111/tpj.12747

An Outlook on Microalgal Biofuels
journal, August 2010


Nitric oxide controls nitrate and ammonium assimilation in Chlamydomonas reinhardtii
journal, July 2013

  • Sanz-Luque, Emanuel; Ocaña-Calahorro, Francisco; Llamas, Angel
  • Journal of Experimental Botany, Vol. 64, Issue 11
  • DOI: 10.1093/jxb/ert175

Microalgae: The Potential for Carbon Capture
journal, October 2010


Characterizing the Anaerobic Response of Chlamydomonas reinhardtii by Quantitative Proteomics
journal, February 2010

  • Terashima, Mia; Specht, Michael; Naumann, Bianca
  • Molecular & Cellular Proteomics, Vol. 9, Issue 7
  • DOI: 10.1074/mcp.M900421-MCP200

Arrangement of the Multicopy H + -translocating Subunit c in the Membrane Sector of the Escherichia coli F 1 F 0 ATP Synthase
journal, July 1998

  • Jones, Phil C.; Jiang, Weiping; Fillingame, Robert H.
  • Journal of Biological Chemistry, Vol. 273, Issue 27
  • DOI: 10.1074/jbc.273.27.17178

Algae Need Their Vitamins
journal, August 2006

  • Croft, Martin T.; Warren, Martin J.; Smith, Alison G.
  • Eukaryotic Cell, Vol. 5, Issue 8
  • DOI: 10.1128/EC.00097-06

A protocol for generating a high-quality genome-scale metabolic reconstruction
journal, January 2010


The Chlamydomonas genome project: a decade on
journal, October 2014


C HLAMYDOMONAS AS A M ODEL O RGANISM
journal, June 2001


Retrograde bilin signaling enables Chlamydomonas greening and phototrophic survival
journal, January 2013

  • Duanmu, Deqiang; Casero, David; Dent, Rachel M.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 9
  • DOI: 10.1073/pnas.1222375110

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


The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions
journal, October 2007

  • Merchant, S. S.; Prochnik, S. E.; Vallon, O.
  • Science, Vol. 318, Issue 5848, p. 245-250
  • DOI: 10.1126/science.1143609

The challenges of in silico biology
journal, November 2000

  • Palsson, Bernhard
  • Nature Biotechnology, Vol. 18, Issue 11
  • DOI: 10.1038/81125

Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use
journal, October 1994


Flux balance analysis of primary metabolism in Chlamydomonas reinhardtii
journal, January 2009


Characterization of an internal type-II NADH dehydrogenase from Chlamydomonas reinhardtii mitochondria
journal, July 2012


The KEGG databases at GenomeNet
journal, January 2002


Biodiesel from microalgae
journal, May 2007


Metabolite Profiling and Integrative Modeling Reveal Metabolic Constraints for Carbon Partitioning under Nitrogen Starvation in the Green Algae Haematococcus pluvialis
journal, September 2014

  • Recht, Lee; Töpfer, Nadine; Batushansky, Albert
  • Journal of Biological Chemistry, Vol. 289, Issue 44
  • DOI: 10.1074/jbc.M114.555144

The Mitochondrial Oxidative Phosphorylation Proteome of Chlamydomonas reinhardtii Deduced from the Genome Sequencing Project: Table I.
journal, February 2005

  • Cardol, Pierre; González-Halphen, Diego; Reyes-Prieto, Adrian
  • Plant Physiology, Vol. 137, Issue 2
  • DOI: 10.1104/pp.104.054148

Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana
journal, December 2008


Oxidative stress, antioxidants and stress tolerance
journal, September 2002


Proton-powered turbine of a plant motor
journal, May 2000

  • Seelert, Holger; Poetsch, Ansgar; Dencher, Norbert A.
  • Nature, Vol. 405, Issue 6785
  • DOI: 10.1038/35013148

Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli
journal, May 2005


The Oligomeric State of c Rings from Cyanobacterial F-ATP Synthases Varies from 13 to 15
journal, June 2007

  • Pogoryelov, D.; Reichen, C.; Klyszejko, A. L.
  • Journal of Bacteriology, Vol. 189, Issue 16
  • DOI: 10.1128/JB.00581-07

Hypoxic survival requires a 2-on-2 hemoglobin in a process involving nitric oxide
journal, June 2013

  • Hemschemeier, A.; Duner, M.; Casero, D.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
  • DOI: 10.1073/pnas.1302592110

Shrinking the Metabolic Solution Space Using Experimental Datasets
journal, August 2012


Systems and Trans -System Level Analysis Identifies Conserved Iron Deficiency Responses in the Plant Lineage
journal, October 2012

  • Urzica, Eugen I.; Casero, David; Yamasaki, Hiroaki
  • The Plant Cell, Vol. 24, Issue 10
  • DOI: 10.1105/tpc.112.102491

Applications of genome‐scale metabolic reconstructions
journal, January 2009

  • Oberhardt, Matthew A.; Palsson, Bernhard Ø; Papin, Jason A.
  • Molecular Systems Biology, Vol. 5, Issue 1
  • DOI: 10.1038/msb.2009.77

Basic and applied uses of genome‐scale metabolic network reconstructions of Escherichia coli
journal, January 2013

  • McCloskey, Douglas; Palsson, Bernhard Ø; Feist, Adam M.
  • Molecular Systems Biology, Vol. 9, Issue 1
  • DOI: 10.1038/msb.2013.18

Defining functional DNA elements in the human genome
journal, April 2014

  • Kellis, M.; Wold, B.; Snyder, M. P.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 17
  • DOI: 10.1073/pnas.1318948111

iMAT: an integrative metabolic analysis tool
journal, November 2010


Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps
journal, April 2011

  • Castruita, Madeli; Casero, David; Karpowicz, Steven J.
  • The Plant Cell, Vol. 23, Issue 4
  • DOI: 10.1105/tpc.111.084400

Integration of transcriptomics and metabolomics data specifies the metabolic response of Chlamydomonas to rapamycin treatment
journal, February 2015

  • Kleessen, Sabrina; Irgang, Susann; Klie, Sebastian
  • The Plant Journal, Vol. 81, Issue 5
  • DOI: 10.1111/tpj.12763

Predotar: A tool for rapidly screening proteomes forN-terminal targeting sequences
journal, June 2004


Interpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production
journal, August 2009


From RNA-seq reads to differential expression results
journal, January 2010


Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation
journal, April 2007

  • Park, J. H.; Lee, K. H.; Kim, T. Y.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 19, p. 7797-7802
  • DOI: 10.1073/pnas.0702609104

Identification of the peroxisomal targeting signal for cottonseed catalase
journal, August 1997


    Works referencing / citing this record:

    Current status and applications of genome-scale metabolic models
    journal, June 2019


    Development of a Chlamydomonas reinhardtii metabolic network dynamic model to describe distinct phenotypes occurring at different CO 2 levels
    journal, January 2018

    • Mora Salguero, Daniela Alejandra; Fernández-Niño, Miguel; Serrano-Bermúdez, Luis Miguel
    • PeerJ, Vol. 6
    • DOI: 10.7717/peerj.5528

    Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii
    journal, May 2017


    Algal Cell Factories: Approaches, Applications, and Potentials
    journal, December 2016

    • Fu, Weiqi; Chaiboonchoe, Amphun; Khraiwesh, Basel
    • Marine Drugs, Vol. 14, Issue 12
    • DOI: 10.3390/md14120225

    Reconstruction and analysis of a carbon-core metabolic network for Dunaliella salina
    journal, January 2020


    Traceability, reproducibility and wiki-exploration for “à-la-carte” reconstructions of genome-scale metabolic models
    journal, May 2018


    Metabolic modelling and simulation of the light and dark metabolism of Chlamydomonas reinhardtii
    journal, October 2018

    • Shene, Carolina; Asenjo, Juan A.; Chisti, Yusuf
    • The Plant Journal, Vol. 96, Issue 5
    • DOI: 10.1111/tpj.14078

    Current status and applications of genome-scale metabolic models
    journal, June 2019


    Reconstruction of the microalga Nannochloropsis salina genome-scale metabolic model with applications to lipid production
    journal, July 2017

    • Loira, Nicolás; Mendoza, Sebastian; Paz Cortés, María
    • BMC Systems Biology, Vol. 11, Issue 1
    • DOI: 10.1186/s12918-017-0441-1