Abstract
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 d-glucose case as a point of reference, we then proceed to discuss the known signaling response to d-xylose in S. cerevisiae and current attempts of improving the response by signaling engineering using native targets and synthetic (non-native) regulatory circuits.
Highlights
Metabolic engineering has enabled various microorganisms to grow on and convert non-native carbon sources into useful bulk and fine chemicals through recombinant expression of heterologous pathways identified in other species
A current hypothesis suggests that SNF1 deactivates TOR complex 1 (TORC1) by phosphorylation of the Kog1p subunit during D-glucose starvation [184,190], i.e., the D-glucose sensing is achieved via SNF1/Mig1p pathway cross-talk (Figure 4)
Since cross-talk with the cyclic AMP (cAMP)/protein kinase A (PKA) and SNF1/Mig1p pathways has been established for both the filamentous growth and target of rapamycin (TOR) pathways to trigger nutrient scavenging during nutrient limitations and to regulate growth promotion during nutrient availability, respectively, there is a possibility that D-xylose affects the signaling in these pathways differently to D-glucose
Summary
Metabolic engineering has enabled various microorganisms to grow on and convert non-native carbon sources into useful bulk and fine chemicals through recombinant expression of heterologous pathways identified in other species. An increasing number of studies have pointed to the unusual physiological response to D-xylose in the xylose-engineered yeast strains: the cells ferment ethanol from D-xylose but exhibit a respiratory response while doing so [34,35,36,37,38]. This has led to the hypothesis that S. cerevisiae may not recognize this foreign pentose sugar as a fermentable sugar [37]. The currently known effects of Dxylose on the sugar signaling networks in wild-type and XR/XDH- or XI-engineered yeast strains are summarized (Section 4), with special emphasis on how they differ from the Dglucose response. The current and future states of D-xylose signaling engineering are discussed from three different but complementary perspectives: engineering the native signaling network, constructing synthetic signaling circuits, and computational modeling of sugar signaling (Section 5)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
