(495b) Improving Exogenous Sugar Utilization by Engineered Transporters

Metabolic engineering is a powerful platform for controlling cellular production of biomolecules.  However, classical metabolic engineering tools do not address molecular transport across the cellular membrane – the key first step in many pathways.  Molecular transport is rarely an issue when an organism utilizes its preferred carbon source, yet limitation is clearly evident when altering the carbon source preferences of an organism.  As an example, molecular transport limits pentose utilization in Saccharomyces cerevisiae, an important problem in lignocellulosic biomass conversion to biofuels. Due to the lack of specific D-xylose and L-arabinose transporters, pentose uptake occurs via hexose transporters.  Metabolic flux is limited by low pentose affinity and hexose inhibition.  Here, we present evidence that heterologous proteins may be engineered using directed evolution to improve S. cerevisiae pentose growth characteristics and ultimately biofuels production.  This study provides interesting insight into the possibility of molecular transporter engineering to improve metabolic pathways.