Team:Evry/Metabolism model

Introduction

In this part of our modeling work we focus on genome scale analysis of the enterobactin production pathway. A major concern about our system is its non-orthogonality with the natural metabolic network of the cells : E.Coli already possesses the genes for producing enterobactins. Therefore we wanted to assess the possible interactions between our system and the bacterial metabolism.

Observations

This model stems from the following observations :

• Enterobactin production pathway is a metabolic process;
• Any of the involved metabolites may limit the rate of the reactions.

The Figure 1 presents the biochemical pathway for producing the enterobactin compound in E.coli.

As can be seen in the figure the pathway is 4 steps long and composed of six different enzymes. Hence there exists 4 possible metabolites which concentration may be limiting :

• Chorismate
• Isochorismate
• 2,3-dihydroxy-2,3-dihydrobenzoate
• 2,3-dihydroxybenzoat

Goals

We highlighted two main kind of interactions between the bacterial and our system :

1. The synthetic system interacts with the bacterial metabolism. Leading to scarcity of the metabolites involved in the pathway for the other (possibly essential) metabolic reactions of the cell.
2. The other way round, the metabolic reactions could prevent our synthetic system to work as expected by limiting the quantity of the involved metabolites available.

From these assumptions we formulated the following questions :

• Is the metabolic model of E.coli able to provide any information about the possible interactions between our system and the metabolism?
• Is the concentration of any metabolite limiting ?
• In the latter case, what is the quantity of this metabolite to add?

Materials and Methods

Model

We used the metabolic model E.Coli iJR904 downloaded from the BiGG model database (http://bigg.ucsd.edu/bigg/home.pl). We chose this model because it contains all the metabolites involved in the enterobactin production pathway.

This model contains 4037 reactions and 625 metabolites but lacks the enterobactin syntase(the last reaction of the enterobactin production pathway).

Site developped by Gabriel Guillocheau