(582bz) Rewiring Yeast Sugar Transporter Preference Through Modifying a Conserved Protein Motif

Metabolic engineering is a powerful platform for controlling cellular production of biomolecules.  However, the field is still limited by few effective methods to alter the carbon source preference of an organism.  For the case of lignocellulosic biomass conversion, recombinant strains of Saccharomyces cerevisiae are limited in their catabolism of xylose.  Specifically, both sugar transport and assimilation steps limit pentose utilization in these strains.  While much progress has been made in altering the pentose catabolic steps, transporter engineering has only recently been shown to be effective.  In this talk, we will discuss efforts in the identification, directed evolution, and rational modification of major facilitator superfamily transporters for improved xylose uptake in S. cerevisiae.  In particular, through this work, we have identified a conserved motif that is responsible for sugar transport efficiency and selectivity.  By modifying this region, we have rewired the function of a transporter from a generalist capable of transporting both glucose and xylose into a specialist that is only able to support the transport of xylose.  This engineering of the first yeast xylose transporter capable of supporting robust cell growth is of strong interest for biofuels applications.  Additionally, this work has increased the overall understanding of yeast sugar transporters and represents another step forward for molecular transporter engineering.