基于文献挖掘的巨大芽胞杆菌代谢网络模型的构建与分析

Reconstruction and analysis of Bacillus megaterium metabolic model based on literature study

【目的】通过挖掘实验性文献,建立巨大芽胞杆菌事实型代谢网络模型,以详尽解析生理特性,优化其生理功能。【方法】从PubMed、Derwent Innovations Index、中国知网等公共文献(专利)数据库中获取与巨大芽胞杆菌(Bacillus megaterium)相关的实验性文献建立本地文献数据库。采用文献挖掘工具获取功能基因、酶、代谢物和生化反应等信息,以其为基础构建代谢网络粗模型,进一步借助KEGG等数据库修正以及Matlab程序的模拟得到精细模型(系统生物学标记语言的形式)。【结果】最终的精细模型共有292个生化反应、378个代谢物、220个酶和217个基因。以1.62 mmol/g cell/h的葡萄糖底物吸收速率为限制性条件,模拟的菌体比生长速率为0.089 h-1,略低于实验值0.11 h-1。此外,嘧啶代谢途径的单基因敲除模拟结果表明,准确率为90%。【结论】该代谢网络模型涵盖了中心代谢途径、维生素B12合成途径和氨基酸代谢途径,并在一定程度上反映了营养底物与基因对巨大芽胞杆菌生长性能的影响。

[ Objective] The aim of this study is to reconstruct the metabolic model of Bacillus megaterium by literature study, which would be used to elucidate physiological properties in detail and refine physiological functions. [ Methods] We built a literature database by searching B. megaterium related literatures from Web of Science, PubMed, United States Patent and Trademark Office （USPTO） Patent Databases, Derwent Innovations Index and China National Knowledge Infrastructure （CNKI）. Depending on this database, we extracted the functional genes, enzymes, metabolites and metabolic reactions （including transport reactions） through literature studies. Then, we filled gaps through KEGG Mapper and adding sink reactions. The operation of Matlab programs reconstructed the metabolic model （in the form of Systems Biology Markup Language） of B. megaterium. [ Results] The refined metabolic network model contained 292 metabolic reactions, 378 metabolites, 220 enzymes and 217 genes. With the restrictive condition of 1.62 mmol/g cell/h of glucose uptake rate, the simulated specific growth rate was 0. 089 h^-1, a little lower than the experimental value 0. 11 h^-1. In addition, the accuracy of the single gene deletion simulation in pyrimidine metabolism reached 90%. [ Conclusion] The final metabolic network model covered the biochemical information of citrate cycle, glycolysis, pentose phosphate pathway, fatty acid metabolism, vitamin B_12 biosynthesis and amino acid biosynthesis, and reflected the effect of substrates and genes on the growth of the bacterium to a certain extent.