Engineering Prokaryotic Transcriptional Activator XylR as a Xylose-Inducible Biosensor for Transcription Activation in Yeast

Wei, Wenping; Shang, Yanzhe; Zhang, Ping; Liu, Yong; You, Di; Yin, Bin‐Cheng; Ye, Bang‐Ce

doi:10.1021/acssynbio.0c00122

Cited by 30 publications

(23 citation statements)

References 30 publications

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“…Synthetic signaling networks are defined as either: (i) a cascade of novel signaling events, or (ii) a set of exogenous or engineered TFs with new specificities and signals. Two different strategies for building synthetic D-xylose signal circuits in S. cerevisiae have so far been attempted: the first uses the bacterial transcription factor XylR [301][302][303] and the second uses a modified version of the native S. cerevisiae GAL regulon [259].…”

Section: Synthetic D-xylose Signaling Networkmentioning

confidence: 99%

“…UAS: upstream activating sequence; TATA: TATA-box cis-regulatory element; YFG: Your Favorite Gene. Adapted from [259,302,303,306].…”

Section: Xylr-based Signaling Circuitsmentioning

confidence: 99%

“…The second type of XylR, the gene expression-inducing XylR-I, was recently implemented in Yarrowia lipolytica and S. cerevisiae [303]. Whereas the XylR-R strategy relies on the XylR-R binding to the xylO motif and blocking transcription, expression of XylR-I in eukaryotes requires a fusion of the XylR protein to an activator domain capable of recruiting the endogenous RNA polymerase II (Figure 7B).…”

Section: Xylr-based Signaling Circuitsmentioning

confidence: 99%

“…Whereas the XylR-R strategy relies on the XylR-R binding to the xylO motif and blocking transcription, expression of XylR-I in eukaryotes requires a fusion of the XylR protein to an activator domain capable of recruiting the endogenous RNA polymerase II (Figure 7B). A synthetic promoter with a xylO-I site, recognized by XylR-I, added upstream of the native TEF1 promoter was used to drive GFP expression [303]. Mutant XylR-Is with higher affinity to their DNA-binding motif and strong induction response have also been identified in E. coli [277,310] and shown to have an alleviating effect on CCR [277], but these mutations remain to be tested in S. cerevisiae.…”

Section: Xylr-based Signaling Circuitsmentioning

confidence: 99%

“…However, synthetic D-xylose signaling in S. cerevisiae is still at its infancy with a level of complexity many factors lower than the multi-element cascades of the native sugar signaling networks. The XylR circuits, for instance, which could be considered the only fully synthetic D-xylose signaling circuit in S. cerevisiae to date since all its regulatory elements (XylR and xylO) are of exogenous origin, only cover the final step of a gene regulating signaling cascade:TF-controlled gene expression [301][302][303]305,306]. However, since the different XylR strategies remain to be applied to drive D-xylose utilization, it is currently not known if a circuit containing a single signaling element (the XylR) is enough to improve D-xylose utilization in S. cerevisiae, which is the case in e.g., E. coli [275]; more complex circuits with several signaling elements or loops might instead be required to reach a sufficient regulation.…”

Section: Future Directions For Synthetic D-xylose Signaling Networkmentioning

confidence: 99%

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D-Xylose Sensing in Saccharomyces cerevisiae: Insights from D-Glucose Signaling and Native D-Xylose Utilizers

Brink

Borgström

Persson

et al. 2021

IJMS

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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.

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