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基于代谢网络分析的基因组最小化方法及其在大肠杆菌中的应用

[Genome minimization method based on metabolic network analysis and its application to Escherichia coli].

作者信息

Tang Bincai, Hao Tong, Yuan Qianqian, Chen Tao, Ma Hongwu

机构信息

Department of Biochemical Engineering, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China.

出版信息

Sheng Wu Gong Cheng Xue Bao. 2013 Aug;29(8):1173-84.

Abstract

The minimum life is one of the most important research topics in synthetic biology. Minimizing a genome while at the same time maintaining an optimal growth of the cells is one of the important research objectives in metabolic engineering. Here we propose a genome minimization method based on genome scale metabolic network analysis. The metabolic network is minimized by first deleting the zero flux reactions from flux variability analysis, and then by repeatedly calculating the optimal growth rates after combinatorial deletion of the non-essential genes in the reduced network. We applied this method to the classic E. coli metabolic network model ---iAF1260 and successfully reduced the number of genes in the model from 1 260 to 312 while maintaining the optimal growth rate unaffected. We also analyzed the metabolic pathways in the network with the minimized number of genes. The results provide some guidance for the design of wet experiments to obtain an E. coli minimal genome.

摘要

最小基因组是合成生物学中最重要的研究课题之一。在维持细胞最佳生长的同时使基因组最小化是代谢工程的重要研究目标之一。在此,我们提出一种基于基因组规模代谢网络分析的基因组最小化方法。首先通过通量变异性分析删除零通量反应来使代谢网络最小化,然后在简化网络中对非必需基因进行组合删除后反复计算最佳生长速率。我们将此方法应用于经典的大肠杆菌代谢网络模型——iAF1260,并成功将模型中的基因数量从1260个减少到312个,同时保持最佳生长速率不受影响。我们还分析了基因数量最少的网络中的代谢途径。这些结果为设计获得大肠杆菌最小基因组的湿实验提供了一些指导。

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