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Metabolic Pathways

Metabolic Route Screening

Situation

A microbial process team is screening two simplified routes for a target chemical. Carbon enters through substrate uptake and glycolysis, then can move through an aerobic/TCA branch or an overflow fermentation branch. The aerobic branch supports more target-product flux but depends on oxygen transfer and cooling. Overflow uses less aeration, but sends more material into byproducts. Both branches pass through the same recovery step.

Decision

Which route carries product flux once oxygen transfer, media spend, glycolysis throughput, and product recovery are all active? If aeration increases, does product flux rise, or does another limit take over first?

How we modeled it

The template is a small route-screening network: substrate uptake -> glycolysis -> aerobic or overflow -> product recovery -> target product. Edges carry flux in mmol/gDW/hr with route-specific capacity and cost. Constraints cap product flux, media spend, glycolysis throughput, and aerobic capacity; the solve maximizes target-product flux and reports which limits bind.

What the model shows
Solved route mixAerobic until O₂ caps
Target product flux4.8 mmol/gDW/hr
Next lever+1 aeration step shifts flux to aerobic
Active limits
  • Aerobic capacity at O₂ limit
  • Media budget 88% used
What this shows

Aerobic carries flux until oxygen transfer binds. Overflow remains available, but it is not the first route to expand while aerobic capacity still has value. If aeration increases by one step, more flux moves through the aerobic branch.

Aerobic routing carries the higher-value flux, but only while oxygen transfer can support it.
Overflow is useful capacity when oxygen binds, but it does not remove the aeration constraint.
The first bench check to price is a small aeration-capacity increase, then re-solve for the next active limit.