Optogenetics in Metabolic Engineering

The optimization of engineered metabolic pathways requires careful control over the levels and timing of metabolic enzyme expression. Optogenetic tools are ideal for achieving such precise control, as light can be applied and removed instantly without complex media changes. Here we show that light-controlled transcription can be used to enhance the biosynthesis of valuable products in engineered Saccharomyces cerevisiae. We developed new optogenetic circuits to shift cells from a light-induced growth phase to a dark-induced production phase, which overcomes the challenges associated with light stimulation of high-cell-density fermentations. Furthermore, optogenetic control of engineered pathways enables a new mode of bioreactor operation using periodic light pulses to tune enzyme expression during fermentation and increase yields. Using these advances, we engineered the mitochondrial isobutanol pathway to produce record-breaking levels of isobutanol and 2-methyl-1-butanol micro-aerobically from glucose. These results make a compelling case for the application of optogenetics to metabolic engineering for valuable products.