General concept

The intracellular concentration of macromolecules in a cell can influence physiology. Thus, it is expected that cells may tend to balance this constraint with desired pathway usage. To model this the choice of pathway usage, cytoplasmic crowding can act as a constraint on flux balance simulations. In FBAwMC, a parameter is defined which acts as a rough estimate of the combination of enzyme volume, enzyme concentration, kinetic parameters, cell mass, and cell volume. An average value of this parameter <a> is used, and the sum of the product of this value with all model fluxes is constrained to be less than 1. This value allows the model to recapitulate growth on different substrates and substrate preference in a complex media mixture. While there is no clear regulatory mechanism imposing the molecular crowding constraint, it is interesting that there has been evolutionary selection for an optimized distribution of enzymes that provides the optimal usage of enzymes subject to a limitation of space in the cell.

Items to consider when implementing

Software packages with this method

Applications of interest

Description of study and link to study:

What was learned with this method:

Relevant references

Beg, et al.

Related methods

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