Optimizing metabolic pathways by screening for feasible synthetic reactions

Bio Systems
Georg BaslerZoran Nikoloski

Abstract

Reconstruction of genome-scale metabolic networks has resulted in models capable of reproducing experimentally observed biomass yield/growth rates and predicting the effect of alterations in metabolism for biotechnological applications. The existing studies rely on modifying the metabolic network of an investigated organism by removing or inserting reactions taken either from evolutionary similar organisms or from databases of biochemical reactions (e.g., KEGG). A potential disadvantage of these knowledge-driven approaches is that the result is biased towards known reactions, as such approaches do not account for the possibility of including novel enzymes, together with the reactions they catalyze. Here, we explore the alternative of increasing biomass yield in three model organisms, namely Bacillus subtilis, Escherichia coli, and Hordeum vulgare, by applying small, chemically feasible network modifications. We use the predicted and experimentally confirmed growth rates of the wild-type networks as reference values and determine the effect of inserting mass-balanced, thermodynamically feasible reactions on predictions of growth rate by using flux balance analysis. While many replacements of existing reactions naturally lead to ...Continue Reading

References

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Citations

Sep 11, 2012·Bioinformatics·Abdelhalim LarhlimiZoran Nikoloski
Nov 6, 2012·Plant Biology·C PeterhanselR F Sage
Aug 2, 2015·Trends in Biotechnology·Hugo F Cueto-RojasJ J Heijnen
Dec 18, 2014·Plant Physiology·Chang-Peng XinXin-Guang Zhu

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