Genetic modification of flux for flux prediction of mutants
Genetic modification of flux for flux prediction of mutants
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DOI：
10.1093/bioinformatics/btp298
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发表时间：
2009-07-01
期刊：
影响因子：
5.8
通讯作者：
Kurata, Hiroyuki
中科院分区：
文献类型：
--
作者：
Zhao, Quanyu;Kurata, Hiroyuki
动机：基因缺失和过表达是设计或改善微生物代谢通量分布的关键技术。包括通量平衡分析（FBA）和代谢调节最小化（MOMA）在内的一些算法可以从化学计量矩阵中预测一些代谢基因缺失或无功能突变体的通量分布，但很少有算法可以预测广泛的遗传变化。阳离子，如代谢基因的过表达和过表达，在代谢通量水平上改变突变体的表型。结果：为了克服这些现有的限制，我们开发了一种基于初等模式分析的新算法，该算法可以预测具有广泛基因修饰的突变体的通量分布。它被称为通量的遗传修饰（GMF），它结合了我们已经开发的两种算法：改进控制有效通量（mCEF）和酶控制通量（ECF）。mCEF是在CEF的基础上提出的，从特定生物学功能的角度来估计基因修饰突变体的基因表达模式。GMF不仅可以预测基因缺失突变体的通量分布，还可以预测大肠杆菌和谷氨酸棒状杆菌中基因过表达和过表达突变体的通量分布。这在广泛的转基因突变体的先验通量预测方面取得了突破。
Motivation: Gene deletion and overexpression are critical technologies for designing or improving the metabolic flux distribution of microbes. Some algorithms including flux balance analysis (FBA) and minimization of metabolic adjustment (MOMA) predict a flux distribution from a stoichiometric matrix in the mutants in which some metabolic genes are deleted or non-functional, but there are few algorithms that predict how a broad range of genetic modi. cations, such as over- and underexpression of metabolic genes, alters the phenotypes of the mutants at the metabolic flux level.Results: To overcome such existing limitations, we develop a novel algorithm that predicts the flux distribution of the mutants with a broad range of genetic modification, based on elementary mode analysis. It is denoted as genetic modification of flux (GMF), which couples two algorithms that we have developed: modified control effective flux (mCEF) and enzyme control flux (ECF). mCEF is proposed based on CEF to estimate the gene expression patterns in genetically modified mutants in terms of specific biological functions. GMF is demonstrated to predict the flux distribution of not only gene deletion mutants, but also the mutants with underexpressed and overexpressed genes in Escherichia coli and Corynebacterium glutamicum. This achieves breakthrough in the a priori flux prediction of a broad range of genetically modified mutants.