Prediction of missing enzyme genes in a bacterial metabolic network -: Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa
Prediction of missing enzyme genes in a bacterial metabolic network -: Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa
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DOI：
10.1111/j.1742-4658.2007.05763.x
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发表时间：
2007-05-01
期刊：
影响因子：
5.4
通讯作者：
Kanehisa, Minoru
中科院分区：
文献类型：
--
作者：
Yamanishi, Yoshihiro;Mihara, Hisaaki;Kanehisa, Minoru
代谢网络是由酶和化合物组成的重要生物网络。然而，大量的代谢途径仍然未知，大多数生物体特异性代谢途径包含许多缺失的酶。我们提出了一种新的方法，利用细菌基因组中可用的基因组和化学信息来识别编码缺失酶的基因。所提出的方法包括两个步骤：（a）估计的功能之间的关联基因的染色体邻近和进化的关联，使用监督网络推理;和（B）选择基因候选人缺失的酶的基础上的原始候选人得分和编码的EC数的化学反应信息。我们应用所提出的方法来推断代谢网络的细菌铜绿假单胞菌从两个基因组数据集：基因位置和系统发育概况。接下来，我们预测了几个缺失的酶基因，以重建赖氨酸降解途径在铜绿假单胞菌使用EC数信息。因此，我们将PA 0266鉴定为推定的5-氨基戊酸氨基转移酶（EC 2.6.1.48），将PA 0265鉴定为推定的戊二酸半醛脱氢酶（EC 1.2.1.20）。为了验证我们的预测，我们进行了生化测定，并检查了预测的基因，PA 0265和PA 0266，在一个耦合反应的产物的活性。我们观察到，预测的基因产物催化预期的反应;当两种基因产物从反应中省略时，没有看到活性。
The metabolic network is an important biological network which consists of enzymes and chemical compounds. However, a large number of metabolic pathways remains unknown, and most organism-specific metabolic pathways contain many missing enzymes. We present a novel method to identify the genes coding for missing enzymes using available genomic and chemical information from bacterial genomes. The proposed method consists of two steps: (a) estimation of the functional association between the genes with respect to chromosomal proximity and evolutionary association, using supervised network inference; and (b) selection of gene candidates for missing enzymes based on the original candidate score and the chemical reaction information encoded in the EC number. We applied the proposed methods to infer the metabolic network for the bacteria Pseudomonas aeruginosa from two genomic datasets: gene position and phylogenetic profiles. Next, we predicted several missing enzyme genes to reconstruct the lysine-degradation pathway in P. aeruginosa using EC number information. As a result, we identified PA0266 as a putative 5-aminovalerate aminotransferase (EC 2.6.1.48) and PA0265 as a putative glutarate semialdehyde dehydrogenase (EC 1.2.1.20). To verify our prediction, we conducted biochemical assays and examined the activity of the products of the predicted genes, PA0265 and PA0266, in a coupled reaction. We observed that the predicted gene products catalyzed the expected reactions; no activity was seen when both gene products were omitted from the reaction.