Figure 8.

Scenario for the application of minimal cut sets. (A) Reaction network under consideration, which is supplied with acetate and glutamate. It is assumed that the production of histidine should be prevented. Histidine is produced from the central metabolism intermediate ribose-5 phosphate (Umbarger 1978). Assuming that it is not possible to entirely knock out the reactions r₁₇ and r₁₈ that directly produce ribose-5 phosphate, the reactions r₁₀–r₁₅ are defined as alternative targets (black reactions). (B) In order to determine minimal cut sets, r₁₀–r₁₅ are added to the subsystem containing the outflow reaction of histidine. From the elementary flux patterns, the minimal cut sets can be obtained. (C) Minimal sets of reactions that need to be knocked out to suppress the production of histidine: (black crosses) MCS1; (dark gray crosses) MCS2; (light gray crosses) MCS3. Subsequently, the minimal cut sets can be ranked according to different criteria, like side effects or required effort to knock out the corresponding genes, to determine the optimal knockout strategy. A list of abbreviations can be found in Supplemental material S2.