Updating the objective function

[Bhushan Dhamale]

Hello. I have added a pathway for the synthesis of a metabolite in the iEK1011 model.

Since the pathway for the synthesis of a reactant required in the first step of the pathway was not available in the model, I added the reactant through a sink reaction. The end-product serves as a metal ion transporter under low and excess metal ion concentrations in the extracellular compartment. I want to update the objective function to include this transporter. However, when I include it in the biomass reaction, the optimizeCbModel output drops to zero (regardless of the value of the vector of weights set for the transporter in the objective function)!

I have two questions:

1. How do I integrate the transporter's function in the model?

2. How do I fix the FBA value dropping to zero on the updated model? What am I doing wrong?

I would really appreciate some guidance with this.

[Ronan M.T. Fleming]

Hi Bhushan,
set the lower bound on the objective that you used to get prior to the
changes you made then use relaxedFBA to find out what the minimal
change to your model should be to enable growth. If that does not
work, you might need gap filling.
Regards,
Ronan

https://opencobra.github.io/cobratoolbox/stable/tutorials/tutorialRelaxedFBABounds.html
https://opencobra.github.io/cobratoolbox/stable/tutorials/tutorialFastGapFill.html

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Mr. Ronan MT Fleming B.V.M.S. Dip. Math. Ph.D.
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[Bhushan Dhamale]

relaxedFBA did the job. Thanks a ton for your help! :)

[Bhushan Dhamale]

Hello Ronan,

After adding the metallophore to the model, I also added divalent zinc ion to the 'e' and 'c' compartments. I then added a transport reaction for the metallophore as:

metallophore_c -> metallophore_e

I then added another transport reaction as:

metallophore_e + zn2_e -> metallophore_c + zn2_c

I then added zn2_c to the objective function. This is where things go awry. For any positive flux of zn2_c, the model now shows me a value of -0.0000 for the optimizeCbModel output. I checked the solution to greater precision but the subsequent digits are all zero as well.

I am not able to run relaxedFBA on it as the model isn't detected as infeasible. 
How do I fix this?

[Ronan M.T. Fleming]

Hi Bhushan,

put a small positive lower bound on the objective then it will be infeasible.

I also suggest to read several chapters in:
Systems Biology: Constraint-based Reconstruction and Analysis
Bernhard Palsson
Cambridge University Press, 2015
https://systemsbiology.ucsd.edu/Publications/Books

Regards,
Ronan

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