D-xylose sensing in saccharomyces cerevisiae: Insights from D-glucose signaling and native D-xylose utilizers

Extension of the substrate range is among one of the metabolic engineering goals for microorganisms used in biotechnological processes because it enables the use of a wide range of raw materials as substrates. One of the most prominent examples is the engineering of baker’s yeast Saccharomyces cerevisiae for the utilization of D-xylose, a five-carbon sugar found in high abundance in lignocellulosic biomass and a key substrate to achieve good process economy in chemical production from renewable and non-edible plant feedstocks. Despite many excellent engineering strategies that have allowed recombinant S. cerevisiae to ferment D-xylose to ethanol at high yields, the consumption rate of D-xylose is still significantly lower than that of its preferred sugar D-glucose. In mixed D-glucose/D-xylose cultivations, D-xylose is only utilized after D-glucose depletion, which leads to prolonged process times and added costs. Due to this limitation, the response on D-xylose in the native sugar signaling pathways has emerged as a promising next-level engineering target. Here we review the current status of the knowledge of the response of S. cerevisiae signaling pathways to D-xylose. To do this, we first summarize the response of the native sensing and signaling pathways in S. cerevisiae to D-glucose (the preferred sugar of the yeast). Using the Dglucose case as a point of reference, we then proceed to discuss the known signaling response to Dxylose in S. cerevisiae and current attempts of improving the response by signaling engineering using native targets and synthetic (non-native) regulatory circuits.