Reconstruction of Erwinia carotovora subsp. atroseptica SCRI1043 Metabolic Network and Its Application in Screening Potential Targets
Abstract: Erwinia carotovora subsp. atroseptica SCRI1043 (Eca SCRI1043) is a widespread phytopathogen that causes blackleg and soft rot disease in potatoes. In this paper, we reconstructed the metabolic network of Eca SCRI1043 based on its genomic information. Through the topology and flux balance analysis, hub nodes of the network were selected. After that TTD database was used to screen those hubs and find out the candidate targets. Undecaprenyl pyrophosphate synthetase (Upps) was chosen to do homology modeling and virtual screening by using the comercialize compounds database provided by specs company. Finally, 73 compounds were screened manually in the top scoring 400 compounds.
文章引用: 王君 , 王成 , 孔德信 , 陈玲玲 (2012) 软腐欧文氏菌代谢网络重构及其在靶标筛选中的应用。 计算生物学， 2， 1-9. doi: 10.12677/hjcb.2012.21001
 远方, 屈淑平, 崔崇士. 一株新的胡萝卜软腐欧文氏菌的分离和鉴定[J]. 微生物学报, 2004, 44(2): 136-140.
 雷玉明, 张建朝, 邢会琴. 几种杀菌剂对胡萝卜软腐欧文氏菌的毒力测定[J]. 长江大学学报(自然版), 2010, 7(3): 3-5.
 B. Elhanan, K. Martin, W. Marcus, et al. Large-scale reconstruction and phylogenetic analysis of metabolic environments. Proceeding of the National Academy of Science USA, 2008, 105(38): 14482- 14487.
 K. Arakawa, Y. Yamada, K. Shinoda, et al. GEM System: Automatic prototyping of cell-wide metabolic pathway models from genomes. BMC Bioinformatics, 2006, 7: 168.
 J. W. Pinney, M. W. Shirley, G. A. McConkey, et al. metaSHARK: Software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella. Nucleic Acids Research, 2005, 33(4): 1399-1409.
 C. S. Henry, M. DeJongh, A. A. Best, et al. High-throughput generation, optimization and analysis of genome-scale metabolic models. Nature Biotechnology, 2010, 28(9): 977-984.
 H. Ma, A. P. Zeng. Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms. Bioinformatics, 2003, 19(2): 270-277.
 M. Huss, P. Holme. Currency and commodity metabolites: Their identification and relation to the modularity of metabolic networks. IET Systems Biology, 2007, 1(5): 280-285.
 王卓, 陈琦, 刘雷. 代谢网络进化过程中拓扑结构与功能之间的关联[J]. 科学通报, 2009, 54(5): 776-782.
 F. Zhu, Z. Shi, C. Qin, et al. Therapeutic target database update 2012: A resource for facilitating target-oriented drug discovery. Nucleic Acids Research, 2012, 40(D1): D1128-1136.
 J. Schellenberger, R. Que, R. M. Fleming, et al. Quantitative prediction of cellular metabolism with constraint-based models: The COBRA toolbox v2.0. Nature Protocols, 2011, 6(9): 1290- 1307.
 P. T. Lang, S. R. Brozell, S. Mukherjee, et al. DOCK 6: Combining techniques to model RNA—small molecule Complexes. RNA, 2009, 15(6): 1219-1230.
 G. M. Morris, R. Huey, W. Lindstrom, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 2009, 30(16): 2785-2791.
 H. Jeong, B. Tombor, R. Albert, Z. N. Oltvai and A. L. Barabási. The large-scale organization of metabolic networks. Nature, 2000, 407(6804): 651-654.
 S. H. Strogatz. Exploring complex networks. Nature, 2001, 410 (6825): 268-276.
 Y.-P. Lu, H.-G. Liu, K.-H. Teng, et al. Mechanism of cis-prenyl- transferase reaction probed by substrate analogues. Biochemical and Biophysical Research Communications, 2010, 400(4): 758- 762
 W. Sinko, C. Oliveira, S. Williams, et al. Applying molecular dynamics simulations to identify rarely sampled ligand-bound conformational states of undecaprenyl pyrophosphate synthase, an antibacterial target. Chemical Biology & Drug Desigh, 2011, 77 (6): 412-420
 C. J. Kuo, R. T. Guo, I. L. Lu, et al. Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases. Journal of Biomedicine and Biotechnology, 2008: Article ID 841312.
 R. T. Guo, T. P. Ko, A. P. Chen, et al. Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, lsopentenyl pyrophosphate, and farnesyl thiopyrophosphate: Roles of the metal ion and conserved residues in catalysis. The Journal of Biological Chemistry, 2005, 280(21): 20762-20774.