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Bioinformatics Advance Access published online on May 25, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp298
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genetic Modification of Flux (GMF) for Flux Prediction of Mutants

Quanyu Zhao 1 and Hiroyuki Kurata 1,*

1Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan

*To whom correspondence should be addressed. Prof. Hiroyuki Kurata, E-mail: kurata{at}bio.kyutech.ac.jp


  Abstract

Motivation: Gene deletion and over-expression are critical technologies for de-signing or improving the metabolic flux distribution of microbes. Some algorithms including flux balance analysis (FBA) and minimization of metabolic adjustment (MOMA) predict a flux dis-tribution 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 modifications, such as over-expression and under-expression 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 under-expressed and over-expressed genes in Escherichia coli and Corynebacterium glutamicum. This achieves breakthrough in the a priori flux prediction of a broad range of genetically modified mutants.

Contact: kurata{at}bio.kyutech.ac.jp

Supplementary information: supplementary file and programs are available at the journal's website or http://www.cadlive.jp

Associate Editor: Dr. Trey Ideker

Received on December 3, 2008; revised on April 1, 2009; accepted on April 28, 2009

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