标题:
软腐欧文氏菌代谢网络重构及其在靶标筛选中的应用Reconstruction of Erwinia carotovora subsp. atroseptica SCRI1043 Metabolic Network and Its Application in Screening Potential Targets
作者:
王君, 王成, 孔德信, 陈玲玲
关键字:
胡萝卜软腐欧文氏菌, 代谢网络重构, 流平衡分析, 同源模建, 虚拟筛选Erwinia carotovora subsp. atroseptica SCRI1043; Metabolic Networks; Flux-Balance Analysis; Homology Modeling; Virtual Screening
期刊名称:
《Hans Journal of Computational Biology》, Vol.2 No.1, 2012-03-13
摘要:
欧文氏杆菌(Erwinia)是一类重要的农作物致病细菌，侵染宿主范围广，在世界范围内造成了严重的经济损失，其中Erwinia carotovora subsp. atroseptica SCRI1043 (Eca SCRI1043) 可导致马铃薯感染黑胫软腐病，危害极大。本文构建了Eca SCRI1043基因组的代谢网络，并进行拓扑结构和流平衡分析，以此筛选出网络的中心节点。若中心节点所代表的酶收录在TTD数据库中，则此酶可作为农用杀菌剂的候选靶标。随后选取靶标十一异戊二烯焦磷酸酶(Upps)，采用specs公司的商品化合物数据库作为小分子数据库，对靶标进行高通量虚拟筛选，对综合打分结果最好的前400个化合物进行目筛后得到73种先导化合物，这73种先导化合物可以进一步进行后续生测实验以确定其杀菌活性。
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.