Team:Heidelberg/Templates/Modelling/Ind-Production

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First, we set up a mind model based on the fact that Indigoidine is produced from Glutamine (Glu) that is cyclized (cGlu) <bib id="pmid11790734"/>, and our observation that Indigoidine-producing bacteria grow slower than mock controls. Those hypotheses resulted in a general model scheme depicting the interdependency between Indigoidine synthesis and bacterial growth (Fig. 1). With the mathematical model we could then validate if there is indeed a negative feedback from the Indigoidine production to the growth of bacteria.
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First, we set up a mind model based on the fact that Indigoidine is produced from Glutamine (Glu) that is cyclized (cGlu) <bib id="pmid11790734"/>, and our observation that Indigoidine-producing bacteria grow slower than mock controls. Those hypotheses resulted in a general model scheme depicting the interdependency between Indigoidine synthesis and bacterial growth (Fig. 1). With the mathematical model we could then validate whether there is indeed a negative feedback from the Indigoidine production to the growth of bacteria.
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Revision as of 14:43, 27 October 2013

Challenge

A challenge we had to face during the characterization and optimization of indC was to identify the production kinetics of Indigoidine. In order to disentangle the underlying mechanisms of bacterial growth and peptide synthesis, we decided to set up a mathematical model based on coupled ordinary differential equations (ODEs). Calibrated with our experimental time-resolved data, the mathematical model could potentially not only elucidate how Indigoidine production influences growth of bacteria but also provide a more quantitative understanding of the synthesis efficiency of the different T domains and PPTases that were tested.

Approach

First, we set up a mind model based on the fact that Indigoidine is produced from Glutamine (Glu) that is cyclized (cGlu) , and our observation that Indigoidine-producing bacteria grow slower than mock controls. Those hypotheses resulted in a general model scheme depicting the interdependency between Indigoidine synthesis and bacterial growth (Fig. 1). With the mathematical model we could then validate whether there is indeed a negative feedback from the Indigoidine production to the growth of bacteria.

Mathematical modelling allows for Identifiability analysis We adapted our ODE for bacterial growth from equation (7) of Kenneth and Kamau, 1993 . The ODE system determining the time evolution of the dynamical variables is given by the following four equations:

$$ \mathrm{d}\mathrm{[Bac]}/\mathrm{d}t = -\frac{\mathrm{[Bac]} \cdot \left(\mathrm{[Bac]} - \mathrm{Bacmax\_native\_svp}\right) \cdot \left(\mathrm{beta\_native\_svp} - \mathrm{[Ind]} \cdot \mathrm{ki\_native\_svp}\right)}{\mathrm{Bacmax\_native\_svp}} $$ $$\mathrm{d}\mathrm{[Glu]}/\mathrm{d}t = - \mathrm{[Bac]} \cdot \mathrm{[Glu]} \cdot \mathrm{ksyn\_native\_svp} $$ $$\mathrm{d}\mathrm{[cGlu]}/\mathrm{d}t = - \mathrm{kdim\_native\_svp} \cdot {\mathrm{[cGlu]}}^2 - \mathrm{kdegg\_native\_svp} \cdot \mathrm{[cGlu]} + \mathrm{[Bac]} \cdot \mathrm{[Glu]} \cdot \mathrm{ksyn\_native\_svp} $$ $$\mathrm{d}\mathrm{[Ind]}/\mathrm{d}t = {\mathrm{[cGlu]}}^2 \cdot \mathrm{kdim\_native\_svp} - \mathrm{[Ind]} \cdot \mathrm{kdegi\_native\_svp} $$

Results

Conclusion and Outlook