Optimizing Metabolite Production Using Periodic Oscillations
A. An illustration of a light-inducible regulatory cluster that could be built for oscillating enzymes. The light-repressed two component system, YF-1/FixJ, expressed constitutively from the promoter IQ, controls gene expression from the FixK2 promoter. The lambda repressor protein, Cl, can repress expression from the lambda phage promoter, pR. When the absence of light activates this system, the response regulator, FixJ, is phosphorylated and represses expression of Cl and RPPK, simultaneously increasing expression of GAPDH and PFK. B. Resulting enzyme profiles from oscillating RPPK-GAPDH-PFK circuit for 8 hours. Each enzyme was allowed to reach a maximum of 20 times its steady state levels. C. PEP levels over 8 hours in response to the oscillating enzymes in B. The line with smaller dashes represents PEP levels without oscillating any enzymes (unoptimized case). The line with larger dashes shows the PEP from optimizing the levels of the three enzymes rather than oscillating (PEP time invariant enzyme levels).