Metabolic Engineering of a Biosensor-Based Screening Platform in Yeast

Since its emergence in the 1990s, metabolic engineering has mainly focused on the optimization of certain products that can be converted from biomass feedstock and quickly evolved as an enabling technology for a biosustainable society. Besides, it largely expands the spectrum of products by introducing synthetic metabolic routes into a host cell. Along with the recent advances in synthetic biology, it becomes significantly easier and cheaper to design and assemble regulatory circuits or even complex networks using synthetic parts from a library. Given the diversity of these biochemical reactions, the increasing availability of genome sequences as well as the part libraries being constructed, the capacity of such a combinatorial approach for creating a collection of engineered strains is virtually unlimited. However, this imposes a bottleneck on the screening of the desired characteristics in these synthetic constructs. Here we present our initial work on the development of a biosensor-based screening for yeast strains with optimized supplies of metabolites of interest. The target metabolite can be a general precursor like acetyl-CoA, or a cofactor that is required for proper cell function and must be balanced, such as NADPH. Considering that these key intracellular metabolites also participate in the production of many compounds with vast economic interest, a biosensor as such sees great potentials in the metabolic engineering of yeast cell factories.