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

Title: A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism

Abstract

Phototrophic organisms such as cyanobacteria utilize the sun’s energy to convert atmospheric carbon dioxide into organic carbon, resulting in diurnal variations in the cell’s metabolism. Flux balance analysis is a widely accepted constraint-based optimization tool for analyzing growth and metabolism, but it is generally used in a time-invariant manner with no provisions for sequestering different biomass components at different time periods. Here we present CycleSyn, a periodic model of Synechocystis sp. PCC 6803 metabolism that spans a 12-hr light/12-hr dark cycle by segmenting it into 12 Time Point Models (TPMs) with a uniform duration of two hours. The developed framework allows for the flow of metabolites across TPMs while inventorying metabolite levels and only allowing for the utilization of currently or previously produced compounds. The 12 TPMs allow for the incorporation of time-dependent constraints that capture the cyclic nature of cellular processes. Imposing bounds on reactions informed by temporally-segmented transcriptomic data enables simulation of phototrophic growth as a single linear programming (LP) problem. The solution provides the time varying reaction fluxes over a 24-hour cycle and the accumulation/consumption of metabolites. The diurnal rhythm of metabolic gene expression driven by the circadian clock and its metabolic consequences is explored. Predicted fluxmore » and metabolite pools are in line with published studies regarding the temporal organization of phototrophic growth in Synechocystis PCC 6803 paving the way for constructing time-resolved genome-scale models (GSMs) for organisms with a circadian clock. In addition, the metabolic reorganization that would be required to enable Synechocystis PCC 6803 to temporally separate photosynthesis from oxygen-sensitive nitrogen fixation is also explored using the developed model formalism.« less

Authors:
; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Washington Univ., St. Louis, MO (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1493514
Alternate Identifier(s):
OSTI ID: 1491948; OSTI ID: 1611941
Grant/Contract Number:  
SC0012722
Resource Type:
Published Article
Journal Name:
PLoS Computational Biology (Online)
Additional Journal Information:
Journal Name: PLoS Computational Biology (Online) Journal Volume: 15 Journal Issue: 1; Journal ID: ISSN 1553-7358
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology; Mathematical & Computational Biology

Citation Formats

Sarkar, Debolina, Mueller, Thomas J., Liu, Deng, Pakrasi, Himadri B., Maranas, Costas D., and Steuer, ed., Ralf. A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism. United States: N. p., 2019. Web. doi:10.1371/journal.pcbi.1006692.
Sarkar, Debolina, Mueller, Thomas J., Liu, Deng, Pakrasi, Himadri B., Maranas, Costas D., & Steuer, ed., Ralf. A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism. United States. doi:https://doi.org/10.1371/journal.pcbi.1006692
Sarkar, Debolina, Mueller, Thomas J., Liu, Deng, Pakrasi, Himadri B., Maranas, Costas D., and Steuer, ed., Ralf. Thu . "A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism". United States. doi:https://doi.org/10.1371/journal.pcbi.1006692.
@article{osti_1493514,
title = {A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism},
author = {Sarkar, Debolina and Mueller, Thomas J. and Liu, Deng and Pakrasi, Himadri B. and Maranas, Costas D. and Steuer, ed., Ralf},
abstractNote = {Phototrophic organisms such as cyanobacteria utilize the sun’s energy to convert atmospheric carbon dioxide into organic carbon, resulting in diurnal variations in the cell’s metabolism. Flux balance analysis is a widely accepted constraint-based optimization tool for analyzing growth and metabolism, but it is generally used in a time-invariant manner with no provisions for sequestering different biomass components at different time periods. Here we present CycleSyn, a periodic model of Synechocystis sp. PCC 6803 metabolism that spans a 12-hr light/12-hr dark cycle by segmenting it into 12 Time Point Models (TPMs) with a uniform duration of two hours. The developed framework allows for the flow of metabolites across TPMs while inventorying metabolite levels and only allowing for the utilization of currently or previously produced compounds. The 12 TPMs allow for the incorporation of time-dependent constraints that capture the cyclic nature of cellular processes. Imposing bounds on reactions informed by temporally-segmented transcriptomic data enables simulation of phototrophic growth as a single linear programming (LP) problem. The solution provides the time varying reaction fluxes over a 24-hour cycle and the accumulation/consumption of metabolites. The diurnal rhythm of metabolic gene expression driven by the circadian clock and its metabolic consequences is explored. Predicted flux and metabolite pools are in line with published studies regarding the temporal organization of phototrophic growth in Synechocystis PCC 6803 paving the way for constructing time-resolved genome-scale models (GSMs) for organisms with a circadian clock. In addition, the metabolic reorganization that would be required to enable Synechocystis PCC 6803 to temporally separate photosynthesis from oxygen-sensitive nitrogen fixation is also explored using the developed model formalism.},
doi = {10.1371/journal.pcbi.1006692},
journal = {PLoS Computational Biology (Online)},
number = 1,
volume = 15,
place = {United States},
year = {2019},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: https://doi.org/10.1371/journal.pcbi.1006692

Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Daily Expression Pattern of Protein-Encoding Genes and Small Noncoding RNAs in Synechocystis sp. Strain PCC 6803
journal, June 2014

  • Beck, Christian; Hertel, Stefanie; Rediger, Anne
  • Applied and Environmental Microbiology, Vol. 80, Issue 17
  • DOI: 10.1128/AEM.01086-14

A model of cyclic transcriptomic behavior in the cyanobacterium Cyanothece sp. ATCC 51142
journal, January 2011

  • McDermott, Jason E.; Oehmen, Christopher S.; McCue, Lee Ann
  • Molecular BioSystems, Vol. 7, Issue 8
  • DOI: 10.1039/c1mb05006k

Review: On the analysis and interpretation of correlations in metabolomic data
journal, March 2006


A Model for HCO 3 Accumulation and Photosynthesis in the Cyanobacterium Synechococcus sp : Theoretical Predictions and Experimental Observations
journal, February 1985

  • Badger, Murray R.; Bassett, Mary; Comins, Hugh N.
  • Plant Physiology, Vol. 77, Issue 2
  • DOI: 10.1104/pp.77.2.465

Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal oscillation of central metabolic processes
journal, April 2008

  • Stockel, J.; Welsh, E. A.; Liberton, M.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 16
  • DOI: 10.1073/pnas.0711068105

KEGG: Kyoto Encyclopedia of Genes and Genomes
journal, January 2000

  • Kanehisa, Minoru; Goto, Susumu
  • Nucleic Acids Research, Vol. 28, Issue 1, p. 27-30
  • DOI: 10.1093/nar/28.1.27

Reconstruction and Comparison of the Metabolic Potential of Cyanobacteria Cyanothece sp. ATCC 51142 and Synechocystis sp. PCC 6803
journal, October 2012


Photosynthetic and dark carbon metabolism in unicellular blue-green algae
journal, January 1972

  • Pelroy, R. A.; Bassham, J. A.
  • Archiv f�r Mikrobiologie, Vol. 86, Issue 1
  • DOI: 10.1007/BF00412397

Extreme Pathways and Kirchhoff's Second Law
journal, November 2002


Transcriptome and Proteome Dynamics of a Light-Dark Synchronized Bacterial Cell Cycle
journal, August 2012


The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite
journal, September 2015

  • Huergo, Luciano F.; Dixon, Ray
  • Microbiology and Molecular Biology Reviews, Vol. 79, Issue 4
  • DOI: 10.1128/MMBR.00038-15

Contribution of Network Connectivity in Determining the Relationship between Gene Expression and Metabolite Concentration Changes
journal, April 2014

  • Zelezniak, Aleksej; Sheridan, Steven; Patil, Kiran Raosaheb
  • PLoS Computational Biology, Vol. 10, Issue 4
  • DOI: 10.1371/journal.pcbi.1003572

Predicting Dynamic Metabolic Demands in the Photosynthetic Eukaryote Chlorella vulgaris
journal, September 2017

  • Zuñiga, Cristal; Levering, Jennifer; Antoniewicz, Maciek R.
  • Plant Physiology, Vol. 176, Issue 1
  • DOI: 10.1104/pp.17.00605

Novel Metabolic Attributes of the Genus Cyanothece, Comprising a Group of Unicellular Nitrogen-Fixing Cyanobacteria
journal, October 2011

  • Bandyopadhyay, Anindita; Elvitigala, Thanura; Welsh, Eric
  • mBio, Vol. 2, Issue 5
  • DOI: 10.1128/mBio.00214-11

Phosphoketolase pathway contributes to carbon metabolism in cyanobacteria
journal, December 2015

  • Xiong, Wei; Lee, Tai-Chi; Rommelfanger, Sarah
  • Nature Plants, Vol. 2, Issue 1, Article No. 15187
  • DOI: 10.1038/nplants.2015.187

Quantitative evaluation of the role of a putative CO2-scavenging entity in the cyanobacterial CO2-concentrating mechanism
journal, January 1996


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


Flux Balance Analysis of Ammonia Assimilation Network in E. coli Predicts Preferred Regulation Point
journal, January 2011


Synechocystis sp PCC 6803 strains lacking photosystem I and phycobilisome function.
journal, December 1993


Global Analysis of Circadian Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803
journal, March 2005


Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours.
journal, September 1996

  • Mori, T.; Binder, B.; Johnson, C. H.
  • Proceedings of the National Academy of Sciences, Vol. 93, Issue 19
  • DOI: 10.1073/pnas.93.19.10183

Omic data from evolved E. coli are consistent with computed optimal growth from genome‐scale models
journal, January 2010

  • Lewis, Nathan E.; Hixson, Kim K.; Conrad, Tom M.
  • Molecular Systems Biology, Vol. 6, Issue 1
  • DOI: 10.1038/msb.2010.47

Dynamic cyanobacterial response to hydration and dehydration in a desert biological soil crust
journal, June 2013

  • Rajeev, Lara; da Rocha, Ulisses Nunes; Klitgord, Niels
  • The ISME Journal, Vol. 7, Issue 11
  • DOI: 10.1038/ismej.2013.83

The circadian oscillator in Synechococcus elongatus controls metabolite partitioning during diurnal growth
journal, March 2015

  • Diamond, Spencer; Jun, Darae; Rubin, Benjamin E.
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 15
  • DOI: 10.1073/pnas.1504576112

Dynamic proteomic profiling of a unicellular cyanobacterium Cyanothece ATCC51142 across light-dark diurnal cycles
journal, January 2011

  • Aryal, Uma K.; Stöckel, Jana; Krovvidi, Ravi K.
  • BMC Systems Biology, Vol. 5, Issue 1
  • DOI: 10.1186/1752-0509-5-194

Interpreting correlations in metabolomic networks
journal, December 2003

  • Steuer, R.; Kurths, J.; Fiehn, O.
  • Biochemical Society Transactions, Vol. 31, Issue 6
  • DOI: 10.1042/bst0311476

Nitrogen fixation and respiratory electron transport in the cyanobacterium Cyanothece under different light/dark cycles
journal, December 2013

  • Rabouille, Sophie; Van de Waal, Dedmer B.; Matthijs, Hans C. P.
  • FEMS Microbiology Ecology, Vol. 87, Issue 3
  • DOI: 10.1111/1574-6941.12251

High night temperature strongly impacts TCA cycle, amino acid and polyamine biosynthetic pathways in rice in a sensitivity-dependent manner
journal, July 2015

  • Glaubitz, Ulrike; Erban, Alexander; Kopka, Joachim
  • Journal of Experimental Botany, Vol. 66, Issue 20
  • DOI: 10.1093/jxb/erv352

Effects of light intensity and carbon dioxide on lipids and fatty acids produced by Synechocystis sp. PCC6803 during continuous flow
journal, November 2015


The Entner–Doudoroff pathway is an overlooked glycolytic route in cyanobacteria and plants
journal, April 2016

  • Chen, Xi; Schreiber, Karoline; Appel, Jens
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 19
  • DOI: 10.1073/pnas.1521916113

A Mathematical Model for the Kai-Protein–Based Chemical Oscillator and Clock Gene Expression Rhythms in Cyanobacteria
journal, February 2007

  • Miyoshi, Fumihiko; Nakayama, Yoichi; Kaizu, Kazunari
  • Journal of Biological Rhythms, Vol. 22, Issue 1
  • DOI: 10.1177/0748730406295749

Strategies to maintain redox homeostasis during photosynthesis under changing conditions
journal, April 2005

  • Scheibe, Renate; Backhausen, Jan E.; Emmerlich, Vera
  • Journal of Experimental Botany, Vol. 56, Issue 416
  • DOI: 10.1093/jxb/eri181

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


Flux Balance Analysis of Cyanobacterial Metabolism: The Metabolic Network of Synechocystis sp. PCC 6803
journal, June 2013


Evidence for Intermediate S-States as Initial Phase in the Process of Oxygen-Evolving Complex Oxidation
journal, April 2008


Observing and interpreting correlations in metabolomic networks
journal, May 2003


Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth
journal, July 2017

  • Reimers, Alexandra-M.; Knoop, Henning; Bockmayr, Alexander
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 31
  • DOI: 10.1073/pnas.1617508114

Correlation between Protein and mRNA Abundance in Yeast
journal, March 1999

  • Gygi, Steven P.; Rochon, Yvan; Franza, B. Robert
  • Molecular and Cellular Biology, Vol. 19, Issue 3
  • DOI: 10.1128/MCB.19.3.1720

DRUM: A New Framework for Metabolic Modeling under Non-Balanced Growth. Application to the Carbon Metabolism of Unicellular Microalgae
journal, August 2014


Diurnal Rhythms Result in Significant Changes in the Cellular Protein Complement in the Cyanobacterium Cyanothece 51142
journal, February 2011


Genome-Wide Dynamic Transcriptional Profiling of the Light-to-Dark Transition in Synechocystis sp. Strain PCC 6803
journal, July 2002


Metabolic Flux Analysis in Synechocystis Using Isotope Distribution from 13C-Labeled Glucose
journal, July 2002


Assessing the Metabolic Impact of Nitrogen Availability Using a Compartmentalized Maize Leaf Genome-Scale Model
journal, September 2014


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


Modelling cyanobacteria: from metabolism to integrative models of phototrophic growth
journal, March 2012

  • Steuer, R.; Knoop, H.; Machne, R.
  • Journal of Experimental Botany, Vol. 63, Issue 6
  • DOI: 10.1093/jxb/ers018

Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics
journal, April 2017

  • Bordbar, Aarash; Yurkovich, James T.; Paglia, Giuseppe
  • Scientific Reports, Vol. 7, Issue 1
  • DOI: 10.1038/srep46249

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways
journal, August 2015


Screening of amino acids for carbon and nitrogen enrichments in different strains of the cyanobacterium Nostoc muscorum
journal, January 1984


Rhythms in Energy Storage Control the Ability of the Cyanobacterial Circadian Clock to Reset
journal, August 2014


Dynamic Flux Balance Analysis of Diauxic Growth in Escherichia coli
journal, September 2002


Nutrient acquisition and limitation for the photoautotrophic growth of Synechocystis sp. PCC6803 as a renewable biomass source
journal, September 2010

  • Kim, Hyun Woo; Vannela, Raveender; Zhou, Chao
  • Biotechnology and Bioengineering, Vol. 108, Issue 2
  • DOI: 10.1002/bit.22928

Culturing Synechocystis sp. Strain PCC 6803 with N 2 and CO 2 in a Diel Regime Reveals Multiphase Glycogen Dynamics with Low Maintenance Costs
journal, May 2016

  • Angermayr, S. Andreas; van Alphen, Pascal; Hasdemir, Dicle
  • Applied and Environmental Microbiology, Vol. 82, Issue 14
  • DOI: 10.1128/AEM.00256-16

Knock-out of the Magnesium Protoporphyrin IX Methyltransferase Gene in Arabidopsis : EFFECTS ON CHLOROPLAST DEVELOPMENT AND ON CHLOROPLAST-TO-NUCLEUS SIGNALING
journal, November 2006

  • Pontier, Dominique; Albrieux, Catherine; Joyard, Jacques
  • Journal of Biological Chemistry, Vol. 282, Issue 4
  • DOI: 10.1074/jbc.M610286200

Tetrapyrrole Biosynthesis in Higher Plants
journal, June 2007


Ultradian metabolic rhythm in the diazotrophic cyanobacterium Cyanothece sp. ATCC 51142
journal, July 2013

  • Cerveny, J.; Sinetova, M. A.; Valledor, L.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 32
  • DOI: 10.1073/pnas.1301171110

The Metabolic Network of Synechocystis sp. PCC 6803: Systemic Properties of Autotrophic Growth
journal, July 2010

  • Knoop, Henning; Zilliges, Yvonne; Lockau, Wolfgang
  • Plant Physiology, Vol. 154, Issue 1
  • DOI: 10.1104/pp.110.157198

Respiration accumulates Calvin cycle intermediates for the rapid start of photosynthesis in Synechocystis sp. PCC 6803
journal, August 2014

  • Shimakawa, Ginga; Hasunuma, Tomohisa; Kondo, Akihiko
  • Bioscience, Biotechnology, and Biochemistry, Vol. 78, Issue 12
  • DOI: 10.1080/09168451.2014.943648

What is flux balance analysis?
journal, March 2010

  • Orth, Jeffrey D.; Thiele, Ines; Palsson, Bernhard Ø
  • Nature Biotechnology, Vol. 28, Issue 3
  • DOI: 10.1038/nbt.1614

Visualizing plant metabolomic correlation networks using clique-metabolite matrices
journal, December 2001


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


Light Requirement for Induction and Continuous Accumulation of an Ammonium-Inducible NADP-Specific Glutamate Dehydrogenase in Chlorella
journal, June 1981

  • Molin, William T.; Cunningham, Thomas P.; Bascomb, Newell F.
  • Plant Physiology, Vol. 67, Issue 6
  • DOI: 10.1104/pp.67.6.1250

Net light-induced oxygen evolution in photosystem I deletion mutants of the cyanobacterium Synechocystis sp. PCC 6803
journal, May 2012

  • Wang, Qing Jun; Singh, Abhay; Li, Hong
  • Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1817, Issue 5
  • DOI: 10.1016/j.bbabio.2012.01.004

    Works referencing / citing this record:

    An integrated computational and experimental study to investigate Staphylococcus aureus metabolism
    journal, January 2020

    • Mazharul Islam, Mohammad; Thomas, Vinai C.; Van Beek, Matthew
    • npj Systems Biology and Applications, Vol. 6, Issue 1
    • DOI: 10.1038/s41540-019-0122-3