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Do models use GLC and ACE at the same time #27
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Daniel mentioned a paper by Markus Basan (sp?) that looks at glucose vs acetate fermentation. |
A more difficult/longer-term interesting thing to do is to see what biomass components are coming from which carbon source. If you were doing a wet lab experiment, you could label the sources with different isotopes and see where they end up. How do we do the equivalent in FBA? Follow the fluxes? Escher maps would be very useful. |
I set up COBRA simulations with media that either have only glucose, only acetate or both with:
And then I plotted the fluxes of all reactions involving glucose or acetate as bar charts: I want to dig more into those really large negative fluxes, because at first look it looks like the cell is exporting acetate even when growing on acetate? |
Daniel says to calculate the uptake rates of Glucose and Acetate from the NMR data. |
Markus says that the glyoxylate shunt alone is not enough to explain co-utilization, there has to be some other thing. In H. pylori there was half of the shunt present, but it was actually doing some totally different pathway. |
Zac thinks that the acetate may be going directly into the TCA cycle through acetyl-coA. |
Zac also notes that the 3hb bi-cycle (?) is more highly expressed on acetate. |
Represent data not as agraph, chose the reactiosn that have the highest change and put values in a table. |
Cannot make progress on this until the new MS2 model can grow on the expected carbon source(s). |
Reverted to an older model that grows on both and am using that. To do:
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As I mentioned earlier, I am skeptical of those large negative fluxes for acetate transport. |
To me, that seems like:
But those fluxes don't add up... |
I checked the E. coli model (iJO1366.json), and that had the diffusion reaction (ACtex in the big nomenclature) but no other transport reactions for acetate, so I think we are good to remove the proton symporter reaction. |
I removed the acetate/proton symporter from the model and reran FBA on that new model file to regenerate all the plots. See here. |
Mary Ann/Rogier said that the symporter should probably be there, but should only be able to function going "down" the proton gradient (i.e. moving protons from outside the cell, where they are high, to inside the cell, where they are low). |
I edited that first line of the definition to only allow flux in the forward direction, so that the symporter can only be used for import:
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I made a more digestible graphic comparing E. coli and Amac's growth on single and mixed sources (here mix means the same amount of glucose and acetate as when they were alone). There seems to be slight co-utilization in E. coli and not perfect co-utilization in Amac. Not sure what is going on/what even is expected. |
I have a notebook that makes the maps for the glucose, acetate, and the different mixtures: https://github.com/C-CoMP-STC/mit1002-cue-simulations/blob/e5dff8cec3670b64a825e355e4de2c50fcbe3179/mit1002_full/glc_and_ace/make_escher_plots.ipynb Annoying things:
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Daniel liked the Escher map, but asked if we could label with the human-friendly names rather than the modelSEED IDs. |
Daniel was surprised that Zac said that ALT is using both carbon sources at the same time- thought that you could only choose one or the other.
He said to run COMETS with regular FBA (not pFBA) with the mixed carbon sources and no constraints and see if it uses both.
If it can't use both, that may be a sign that using the two carbon sources at the same time is coming from different sub-populations in the lab.
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