GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism.
GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism.
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DOI：
10.1186/gb-2007-8-5-r89
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
McFadden, Johnjoe
中科院分区：
文献类型：
--
作者：
Beste, Dany J V;Hooper, Tracy;Stewart, Graham;Bonde, Bhushan;Avignone-Rossa, Claudio;Bushell, Michael E;Wheeler, Paul;Klamt, Steffen;Kierzek, Andrzej M;McFadden, Johnjoe
GSMN-TB，M.的基因组规模代谢模型。结核病，构建并使用实验数据验证。合理开发抗结核病（TB）新药的一个障碍是对结核分枝杆菌代谢（特别是感染期间）的知识普遍缺乏。基于约束的建模为研究微生物代谢提供了一种新的方法，但尚未应用于M.结核GSMN-TB是M.结核病，由849个独特的反应和739个代谢产物组成，涉及726个基因。通过在连续培养中生长牛分枝杆菌Calmette Guérin来校准模型，并测量稳态生长参数。通量平衡分析用于计算底物消耗率，这被证明是密切对应于实验确定的值。通过通量平衡分析模拟对基因重要性进行了预测，并与M.体外培养的结核病预测准确率为78%。该模型预测已知的药物靶点是必不可少的。该模型证明了异柠檬酸裂解酶在分枝杆菌缓慢生长过程中的潜在作用，并通过实验验证了这一假设。该模型的交互式网络版本可用。GSMN-TB模型成功地模拟了M.结核该模型提供了一种检测细菌代谢灵活性和预测突变体表型的方法，并突出了以前未探索的M。结核代谢
GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was constructed and validated using experimental data. An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis. GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was constructed, consisting of 849 unique reactions and 739 metabolites, and involving 726 genes. The model was calibrated by growing Mycobacterium bovis bacille Calmette Guérin in continuous culture and steady-state growth parameters were measured. Flux balance analysis was used to calculate substrate consumption rates, which were shown to correspond closely to experimentally determined values. Predictions of gene essentiality were also made by flux balance analysis simulation and were compared with global mutagenesis data for M. tuberculosis grown in vitro. A prediction accuracy of 78% was achieved. Known drug targets were predicted to be essential by the model. The model demonstrated a potential role for the enzyme isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was experimentally verified. An interactive web-based version of the model is available. The GSMN-TB model successfully simulated many of the growth properties of M. tuberculosis. The model provides a means to examine the metabolic flexibility of bacteria and predict the phenotype of mutants, and it highlights previously unexplored features of M. tuberculosis metabolism.