Optogenetics for Temporal and Spatial Control of Microbial Metabolism to Improve Chemical Production

The tunability and reversibility of light signals makes optogenetics a powerful strategy to dynamically and spatially control engineered microbial metabolisms for chemical production. My group has developed transcriptional optogenetic circuits to temporally control the expression of metabolic enzymes during the growth and production phases of microbial fermentations. These circuits can be designed to invert or amplify metabolic responses to light inputs to boost the production of various chemicals. The activation rates of these circuits can have a significant impact on chemical yields and titers, and on our strategies to use open- or closed-loop controls of metabolism; however, we have found ways to manipulate these activation rates to our convenience. To further increase the rates of response to light inputs beyond the limitations imposed by transcription, my group has also developed optogenetic controls that work at post-translational levels. Some of these controls are based on light-dependent assembly of synthetic membraneless organelles, which can be used to co-localize or disperse metabolic enzymes in subcellular space to control flux through branched metabolic pathways. Other systems are based on highly specific protein binders that can be used to control enzymatic activity post-translationally, and can be engineered to be light-switchable. I will discuss how these various optogenetic technologies can be integrated to optimize microbial fermentations for chemical production.