TY - JOUR
T1 - Robustness analysis of a constraint-based metabolic model links cell growth and proteomics of Thermoanaerobacter tengcongensis under temperature perturbation
AU - Tong, Wei
AU - Chen, Zhen
AU - Cao, Zhe
AU - Wang, Quanhui
AU - Zhang, Jiyuan
AU - Bai, Xue
AU - Wang, Rong
AU - Liu, Siqi
PY - 2013/4
Y1 - 2013/4
N2 - The integration of omic data with metabolic networks has been demonstrated to be an effective approach to elucidate the underlying metabolic mechanisms in life. Because the metabolic pathways of Thermoanaerobacter tengcongensis (T. tengcongensis) are incomplete, we used a 1-13C-glucose culture to monitor intracellular isotope-labeled metabolites by GC/MS and identified the gap gene in glucose catabolism, Re-citrate synthase. Based on genome annotation and biochemical information, we reconstructed the metabolic network of glucose metabolism and amino acid synthesis in T. tengcongensis, including 253 reactions, 227 metabolites, and 236 genes. Furthermore, we performed constraint based modeling (CBM)-derived robustness analysis on the model to study the dynamic changes of the metabolic network. By perturbing the culture temperature from 75 to 55 °C, we collected the bacterial growth rates and differential proteomes. Assuming that protein abundance changes represent metabolic flux variations, we proposed that the robustness analysis of the CBM model could decipher the effect of proteome change on the bacterial growth under perturbation. For approximately 73% of the reactions, the predicted cell growth changes due to such reaction flux variations matched the observed cell growth data. Our study, therefore, indicates that differential proteome data can be integrated with metabolic network modeling and that robustness analysis is a strong method for representing the dynamic change in cell phenotypes under perturbation.
AB - The integration of omic data with metabolic networks has been demonstrated to be an effective approach to elucidate the underlying metabolic mechanisms in life. Because the metabolic pathways of Thermoanaerobacter tengcongensis (T. tengcongensis) are incomplete, we used a 1-13C-glucose culture to monitor intracellular isotope-labeled metabolites by GC/MS and identified the gap gene in glucose catabolism, Re-citrate synthase. Based on genome annotation and biochemical information, we reconstructed the metabolic network of glucose metabolism and amino acid synthesis in T. tengcongensis, including 253 reactions, 227 metabolites, and 236 genes. Furthermore, we performed constraint based modeling (CBM)-derived robustness analysis on the model to study the dynamic changes of the metabolic network. By perturbing the culture temperature from 75 to 55 °C, we collected the bacterial growth rates and differential proteomes. Assuming that protein abundance changes represent metabolic flux variations, we proposed that the robustness analysis of the CBM model could decipher the effect of proteome change on the bacterial growth under perturbation. For approximately 73% of the reactions, the predicted cell growth changes due to such reaction flux variations matched the observed cell growth data. Our study, therefore, indicates that differential proteome data can be integrated with metabolic network modeling and that robustness analysis is a strong method for representing the dynamic change in cell phenotypes under perturbation.
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U2 - 10.1039/c3mb25278g
DO - 10.1039/c3mb25278g
M3 - Article
C2 - 23396507
AN - SCOPUS:84874855684
SN - 1742-206X
VL - 9
SP - 713
EP - 722
JO - Molecular BioSystems
JF - Molecular BioSystems
IS - 4
ER -