Abstract
BackgroundIn the present article, we propose a method for determining optimal metabolic pathways in terms of the level of concentration of the enzymes catalyzing various reactions in the entire metabolic network. The method, first of all, generates data on reaction fluxes in a pathway based on steady state condition. A set of constraints is formulated incorporating weighting coefficients corresponding to concentration of enzymes catalyzing reactions in the pathway. Finally, the rate of yield of the target metabolite, starting with a given substrate, is maximized in order to identify an optimal pathway through these weighting coefficients.ResultsThe effectiveness of the present method is demonstrated on two synthetic systems existing in the literature, two pentose phosphate, two glycolytic pathways, core carbon metabolism and a large network of carotenoid biosynthesis pathway of various organisms belonging to different phylogeny. A comparative study with the existing extreme pathway analysis also forms a part of this investigation. Biological relevance and validation of the results are provided. Finally, the impact of the method on metabolic engineering is explained with a few examples.ConclusionsThe method may be viewed as determining an optimal set of enzymes that is required to get an optimal metabolic pathway. Although it is a simple one, it has been able to identify a carotenoid biosynthesis pathway and the optimal pathway of core carbon metabolic network that is closer to some earlier investigations than that obtained by the extreme pathway analysis. Moreover, the present method has identified correctly optimal pathways for pentose phosphate and glycolytic pathways. It has been mentioned using some examples how the method can suitably be used in the context of metabolic engineering.
Highlights
In the present article, we propose a method for determining optimal metabolic pathways in terms of the level of concentration of the enzymes catalyzing various reactions in the entire metabolic network
We provide a comparative analysis of the present method with extreme pathway analysis using two synthetic [12,13] and four different real life pathways
Relevance Here we demonstrate how the results obtained by the present method are biologically more relevant than those obtained by the extreme pathway analysis
Summary
We propose a method for determining optimal metabolic pathways in terms of the level of concentration of the enzymes catalyzing various reactions in the entire metabolic network. A set of constraints is formulated incorporating weighting coefficients corresponding to concentration of enzymes catalyzing reactions in the pathway. Metabolism is a complex process that takes place for producing energy and forms the driving force for cellular activity. It involves a large number of chemical reactions/ conversions carried out by living organisms as they feed, grow and reproduce. A cascade of such reactions/conversions form a highly branched network. A metabolic network consists of many reactions and transport processes associated with the production and depletion of cellular metabolites. Examples of metabolic pathways include Glycolysis, the Krebs cycle and the Pentose phosphate pathways
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