Difference between revisions of "Team:Toulouse/Modeling"

As said before, the aim of our project is to create a biological system able to produce two molecules: butyric acid and formic acid.
To achieve this, we need to modify the existing balance between the metabolic pathways present in E.Coli. Indeed, we want to optimize butyrate and formate productions in our bacterium by adjusting environmental conditions in order to obtain the desired concentrations of the associated acids. The following metabolic network represents all of the known metabolites and metabolic pathways for Escherichia coli K12 MG1655(best known model). It was obtained from KEGG database [1].
Our first step was to identify the pathways in which our molecules take part, in order to have a clear understanding of their role and effect.

Formate is naturally produced by E.coli but at a level that is quite low. Our project requires that Apicoli produces more. Hence we had to optimize its biosynthesis by studying the genes coding for the enzymes involved in the pathway. We decided to focus our efforts on the Pyruvate Formate Lyase (PFL), the enzyme that causes degradation of pyruvate, thus yielding formate.

The subnetwork presented below was obtained from MetExplore platform [2] and presents all reactions from the KEGG and ByoCyc databases involved in the production or consumption of formate. This map will help us predict the likely consequences of a PFL-induced formate overproduction in Apicoli.
In fact, formate is harmful to our bacterium and is normally metabolized to other products. We thus have to find the balance between producing enough formate to kill the varroa without killing Apicoli.

To help ourselves creating Apicoli we modelised our system by using Flux Balance Analysis (FBA) and Flux Variability Analysis (FVA). We used the most recent described model for E.coli K12 MG1655, describing all metabolic pathways known and up to date. This XML file