(479g) Light and Metabolite Biosensors to Study and Engineer Cellular Metabolism (Invited Speaker)

The use of light-responsive biosensors to control biological processes has been called optogenetics. The unmatched spatiotemporal precision, high tunability, reversibility, and few off- target effects of light makes optogenetics a powerful strategy to study and engineer complex biological systems. For these reasons, optogenetics has already revolutionized disciplines such as neuroscience, developmental biology, and cell signaling, and is poised to do the same with cellular metabolism. I will show how we can use light biosensors to control metabolic pathways in Saccharomyces cerevisiae and Escherichia coli. Additionally, I will present a metabolic biosensor for biosynthesis of the branched-chain amino acids (BCAs) valine and leucine, based on a transcription factor activated by an intermediate metabolite. We have used this biosensor to monitor the degradation of BCAs to the branched-chain higher alcohols (BCHAs) isobutanol and isopentanol, sort high-producing strains, and engineer biosynthetic enzymes with enhanced activity. One exciting prospect is the possibility of combining light biosensors with metabolite biosensors to develop closed-loop controls of metabolism. I will present the progress we have made towards this goal for BCA biosynthesis, the challenges that lie ahead, and the opportunities to overcome them in order to realize this new enabling technology to study and engineer metabolic dynamics.