(675b) Modeling, Optimization, and Control of Bioprocesses Using Optogenetics
Optogenetic circuits can be constructed so that light will activate or inhibit a set of genes or metabolic pathways, usually by regulating transcription. Our group has developed a suite of optogenetic circuits for the yeast S. cerevisiae that respond to blue light. These circuits, depending on design, will either activate a gene when blue light is present, or activate a gene when blue light is turned off. Because the circuits are governed by multistep biochemical reaction pathways with different time scales, predicting the circuitâs dynamic response can be challenging. We developed semi-empirical mechanistic models of each of the circuits that enable us to examine the effects of light scheduling on the circuits. Through different light schedules, we can manipulate the expression level of whichever gene is controlled by the circuit. Different light doses, duty cycles, and waveforms were explored to investigate the dynamic behavior of the circuits, helping us uncover design criteria to select control policies for particular applications.
With optogenetic circuits in place for regulating metabolism, a new challenge is the development of an optimal control strategy for higher yields. To address this challenge, we developed a multiscale ordinary differential equation model describing cell growth, consumption of nutrients, production of desired compounds, and the state of the light-actuated metabolic pathway. We analyzed the model and sought forcing strategies that maximized the yield of desired products. In our case studyâcontinuous isobutanol production in yeastâa periodic forcing function was determined to be effective at substantially increasing isobutanol production over any reachable steady-state. This result provides a compelling case for applying optogenetics in metabolic engineering.