Reconstruction of a Genome-Scale Metabolic Model to Simulate Uncoupled Growth of Zymomonas mobilis
Zymomonas mobilis is known as an example of the
uncoupled growth phenomenon. This microorganism also has a
unique metabolism that degrades glucose by the Entner–Doudoroff
(ED) pathway. In this paper, a genome-scale metabolic model
including 434 genes, 757 reactions and 691 metabolites was
reconstructed to simulate uncoupled growth and study its effect on
flux distribution in the central metabolism. The model properly
predicted that ATPase was activated in experimental growth yields of
Z. mobilis. Flux distribution obtained from model indicates that the
major carbon flux passed through ED pathway that resulted in the
production of ethanol. Small amounts of carbon source were entered
into pentose phosphate pathway and TCA cycle to produce biomass
precursors. Predicted flux distribution was in good agreement with
experimental data. The model results also indicated that Z. mobilis
metabolism is able to produce biomass with maximum growth yield
of 123.7 g (mol glucose)-1 if ATP synthase is coupled with growth
and produces 82 mmol ATP gDCW-1h-1. Coupling the growth and
energy reduced ethanol secretion and changed the flux distribution to
produce biomass precursors.
[1] Lee, K.Y., et al., The genome-scale metabolic network analysis of
Zymomonas mobilis ZM4 explains physiological features and suggests
ethanol and succinic acid production strategies. Microbial cell factories,
2010. 9(1): p. 94.
[2] Kalnenieks, U., Physiology of<i> Zymomonas mobilis</i>: Some
Unanswered Questions. Advances in microbial physiology, 2006. 51: p.
73-117.
[3] Rutkis, R., et al., The inefficient aerobic energetics of Zymomonas
mobilis: Identifying the bottleneck. Journal of basic microbiology, 2014.
[4] Kalnenieks, U., et al., Modeling of Zymomonas mobilis central
metabolism for novel metabolic engineering strategies. Frontiers in
microbiology, 2014. 5.
[5] Widiastuti, H., et al., Genome‐scale modeling and in silico analysis of
ethanologenic bacteria Zymomonas mobilis. Biotechnology and
bioengineering, 2011. 108(3): p. 655-665.
[6] Orth, J.D., et al., A comprehensive genome‐scale reconstruction of
Escherichia coli metabolism—2011. Molecular systems biology, 2011.
7(1).
[7] Thiele, I., and B.Ø. Palsson, A protocol for generating a high-quality
genome-scale metabolic reconstruction. Nature protocols, 2010. 5(1): p.
93-121.
[8] Feist, A.M., and B.Ø. Palsson, The growing scope of applications of
genome-scale metabolic reconstructions using Escherichia coli. Nature
biotechnology, 2008. 26(6): p. 659-667.
[9] Seo, J.-S., et al., The genome sequence of the ethanologenic bacterium
Zymomonas mobilis ZM4. Nature biotechnology, 2004. 23(1): p. 63-68.
[10] Yang, S., et al., Improved genome annotation for Zymomonas mobilis.
Nature biotechnology, 2009. 27(10): p. 893-894.
[11] Pentjuss, A., et al., Biotechnological potential of respiring< i>
Zymomonas mobilis</i>: A stoichiometric analysis of its central
metabolism. Journal of biotechnology, 2013. 165(1): p. 1-10.
[12] Keating, S.M., et al., SBMLToolbox: an SBML toolbox for MATLAB
users. Bioinformatics, 2006. 22(10): p. 1275-1277.
[13] Becker, S.A., et al., Quantitative prediction of cellular metabolism with
constraint-based models: the COBRA Toolbox. Nature protocols, 2007.
2(3): p. 727-738.
[14] Kanehisa, M., et al., KEGG for integration and interpretation of largescale
molecular data sets. Nucleic acids research, 2011: p. gkr988.
[15] Karp, P.D., et al., Expansion of the BioCyc collection of
pathway/genome databases to 160 genomes. Nucleic acids research,
2005. 33(19): p. 6083-6089.
[16] Schomburg, I., et al., BRENDA in 2013: integrated reactions, kinetic
data, enzyme function data, improved disease classification: new options
and contents in BRENDA. Nucleic acids research, 2012: p. gks1049.
[17] Ren, Q., K. Chen, and I.T. Paulsen, TransportDB: a comprehensive
database resource for cytoplasmic membrane transport systems and
outer membrane channels. Nucleic acids research, 2007. 35(suppl 1): p.
D274-D279.
[18] Carey, V.C. and L. Ingram, Lipid composition of Zymomonas mobilis:
effects of ethanol and glucose. Journal of bacteriology, 1983. 154(3): p.
1291-1300.
[19] Sahm, H., S. Bringer-Meyer, and G.A. Sprenger, The genus Zymomonas,
in The prokaryotes. 2006, Springer. p. 201-221.
[20] Vincent, S.P., P. Sinay, and M. Rohmer, Composite hopanoid
biosynthesis in Zymomonas mobilis: N-acetyl-D-glucosamine as
precursor for the cyclopentane ring linked to bacteriohopanetetrol.
Chemical Communications, 2003(6): p. 782-783.
[21] Welander, P.V., et al., Identification and characterization of
Rhodopseudomonas palustris TIE‐1 hopanoid biosynthesis mutants.
Geobiology, 2012. 10(2): p. 163-177.
[22] Hayashi, T., T. Kato, and K. Furukawa, Respiratory chain analysis of
Zymomonas mobilis mutants producing high levels of ethanol. Applied
and environmental microbiology, 2012. 78(16): p. 5622-5629.
[23] Goodman, A.E., P.L. Rogers, and M.L. Skotnicki, Minimal medium for
isolation of auxotrophic Zymomonas mutants. Applied and
environmental microbiology, 1982. 44(2): p. 496.
[24] De Graaf, A.A., et al., Metabolic state of Zymomonas mobilis in glucose-
, fructose-, and xylose-fed continuous cultures as analysed by 13C-and
31P-NMR spectroscopy. Archives of microbiology, 1999. 171(6): p.
371-385.
[1] Lee, K.Y., et al., The genome-scale metabolic network analysis of
Zymomonas mobilis ZM4 explains physiological features and suggests
ethanol and succinic acid production strategies. Microbial cell factories,
2010. 9(1): p. 94.
[2] Kalnenieks, U., Physiology of<i> Zymomonas mobilis</i>: Some
Unanswered Questions. Advances in microbial physiology, 2006. 51: p.
73-117.
[3] Rutkis, R., et al., The inefficient aerobic energetics of Zymomonas
mobilis: Identifying the bottleneck. Journal of basic microbiology, 2014.
[4] Kalnenieks, U., et al., Modeling of Zymomonas mobilis central
metabolism for novel metabolic engineering strategies. Frontiers in
microbiology, 2014. 5.
[5] Widiastuti, H., et al., Genome‐scale modeling and in silico analysis of
ethanologenic bacteria Zymomonas mobilis. Biotechnology and
bioengineering, 2011. 108(3): p. 655-665.
[6] Orth, J.D., et al., A comprehensive genome‐scale reconstruction of
Escherichia coli metabolism—2011. Molecular systems biology, 2011.
7(1).
[7] Thiele, I., and B.Ø. Palsson, A protocol for generating a high-quality
genome-scale metabolic reconstruction. Nature protocols, 2010. 5(1): p.
93-121.
[8] Feist, A.M., and B.Ø. Palsson, The growing scope of applications of
genome-scale metabolic reconstructions using Escherichia coli. Nature
biotechnology, 2008. 26(6): p. 659-667.
[9] Seo, J.-S., et al., The genome sequence of the ethanologenic bacterium
Zymomonas mobilis ZM4. Nature biotechnology, 2004. 23(1): p. 63-68.
[10] Yang, S., et al., Improved genome annotation for Zymomonas mobilis.
Nature biotechnology, 2009. 27(10): p. 893-894.
[11] Pentjuss, A., et al., Biotechnological potential of respiring< i>
Zymomonas mobilis</i>: A stoichiometric analysis of its central
metabolism. Journal of biotechnology, 2013. 165(1): p. 1-10.
[12] Keating, S.M., et al., SBMLToolbox: an SBML toolbox for MATLAB
users. Bioinformatics, 2006. 22(10): p. 1275-1277.
[13] Becker, S.A., et al., Quantitative prediction of cellular metabolism with
constraint-based models: the COBRA Toolbox. Nature protocols, 2007.
2(3): p. 727-738.
[14] Kanehisa, M., et al., KEGG for integration and interpretation of largescale
molecular data sets. Nucleic acids research, 2011: p. gkr988.
[15] Karp, P.D., et al., Expansion of the BioCyc collection of
pathway/genome databases to 160 genomes. Nucleic acids research,
2005. 33(19): p. 6083-6089.
[16] Schomburg, I., et al., BRENDA in 2013: integrated reactions, kinetic
data, enzyme function data, improved disease classification: new options
and contents in BRENDA. Nucleic acids research, 2012: p. gks1049.
[17] Ren, Q., K. Chen, and I.T. Paulsen, TransportDB: a comprehensive
database resource for cytoplasmic membrane transport systems and
outer membrane channels. Nucleic acids research, 2007. 35(suppl 1): p.
D274-D279.
[18] Carey, V.C. and L. Ingram, Lipid composition of Zymomonas mobilis:
effects of ethanol and glucose. Journal of bacteriology, 1983. 154(3): p.
1291-1300.
[19] Sahm, H., S. Bringer-Meyer, and G.A. Sprenger, The genus Zymomonas,
in The prokaryotes. 2006, Springer. p. 201-221.
[20] Vincent, S.P., P. Sinay, and M. Rohmer, Composite hopanoid
biosynthesis in Zymomonas mobilis: N-acetyl-D-glucosamine as
precursor for the cyclopentane ring linked to bacteriohopanetetrol.
Chemical Communications, 2003(6): p. 782-783.
[21] Welander, P.V., et al., Identification and characterization of
Rhodopseudomonas palustris TIE‐1 hopanoid biosynthesis mutants.
Geobiology, 2012. 10(2): p. 163-177.
[22] Hayashi, T., T. Kato, and K. Furukawa, Respiratory chain analysis of
Zymomonas mobilis mutants producing high levels of ethanol. Applied
and environmental microbiology, 2012. 78(16): p. 5622-5629.
[23] Goodman, A.E., P.L. Rogers, and M.L. Skotnicki, Minimal medium for
isolation of auxotrophic Zymomonas mutants. Applied and
environmental microbiology, 1982. 44(2): p. 496.
[24] De Graaf, A.A., et al., Metabolic state of Zymomonas mobilis in glucose-
, fructose-, and xylose-fed continuous cultures as analysed by 13C-and
31P-NMR spectroscopy. Archives of microbiology, 1999. 171(6): p.
371-385.
@article{"International Journal of Biological, Life and Agricultural Sciences:73372", author = "Maryam Saeidi and Ehsan Motamedian and Seyed Abbas Shojaosadati", title = "Reconstruction of a Genome-Scale Metabolic Model to Simulate Uncoupled Growth of Zymomonas mobilis", abstract = "Zymomonas mobilis is known as an example of the
uncoupled growth phenomenon. This microorganism also has a
unique metabolism that degrades glucose by the Entner–Doudoroff
(ED) pathway. In this paper, a genome-scale metabolic model
including 434 genes, 757 reactions and 691 metabolites was
reconstructed to simulate uncoupled growth and study its effect on
flux distribution in the central metabolism. The model properly
predicted that ATPase was activated in experimental growth yields of
Z. mobilis. Flux distribution obtained from model indicates that the
major carbon flux passed through ED pathway that resulted in the
production of ethanol. Small amounts of carbon source were entered
into pentose phosphate pathway and TCA cycle to produce biomass
precursors. Predicted flux distribution was in good agreement with
experimental data. The model results also indicated that Z. mobilis
metabolism is able to produce biomass with maximum growth yield
of 123.7 g (mol glucose)-1 if ATP synthase is coupled with growth
and produces 82 mmol ATP gDCW-1h-1. Coupling the growth and
energy reduced ethanol secretion and changed the flux distribution to
produce biomass precursors.", keywords = "Genome-scale metabolic model, Zymomonas
mobilis, uncoupled growth, flux distribution, ATP dissipation.", volume = "8", number = "11", pages = "1306-4", }
