ABSTRACT Whole-cell biocatalysts have proven a tractable path toward sustainable production of bulk and fine chemicals. Yet the screening of libraries of cellular designs to identify

best-performing biocatalysts is most often a low-throughput endeavor. For this reason, the development of biosensors enabling real-time monitoring of production has attracted attention. Here

we applied systematic engineering of multiple parameters to search for a general biosensor design in the budding yeast _Saccharomyces cerevisiae_ based on small-molecule binding

transcriptional activators from the prokaryote superfamily of LysR-type transcriptional regulators (LTTRs). We identified a design supporting LTTR-dependent activation of reporter gene

illustrates the potential of a hitherto untapped biosensor resource useful for biotechnological applications. Access through your institution Buy or subscribe This is a preview of

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AMINO ACID METABOLISM IN YEAST AND APPLICATIONS IN ISOBUTANOL AND ISOPENTANOL PRODUCTION Article Open access 12 January 2022 ENGINEERING AND APPLICATION OF A BIOSENSOR WITH FOCUSED LIGAND

SPECIFICITY Article Open access 25 September 2020 ENGINEERING EUKARYOTE-LIKE REGULATORY CIRCUITS TO EXPAND ARTIFICIAL CONTROL MECHANISMS FOR METABOLIC ENGINEERING IN _SACCHAROMYCES

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Nordisk Foundation and by the European Union Seventh Framework Programme (FP7-KBBE-2013-7-single-stage) under grant agreement no. 613745, Promys (M.E. & S.S.). We acknowledge A. Koza and

E. Özdemir for technical assistance. AUTHOR INFORMATION Author notes * Mette L Skjoedt and Tim Snoek: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * The Novo

Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Hørsholm, Denmark Mette L Skjoedt, Tim Snoek, Kanchana R Kildegaard, Dushica Arsovska, Tobias J Goedecke, 

Arun S Rajkumar, Jie Zhang, Mette Kristensen, Solvej Siedler, Irina Borodina, Michael K Jensen & Jay D Keasling * Evolva SA, Reinach, Switzerland Michael Eichenberger * Department of

Biology, Technical University Darmstadt, Darmstadt, Germany Michael Eichenberger * Evolva Biotech A/S, Copenhagen, Denmark Beata J Lehka * Department of Science and Environment, Roskilde

University, Roskilde, Denmark Beata J Lehka * Joint BioEnergy Institute, Emeryville, California, USA Jay D Keasling * Physical Biosciences Division, Lawrence Berkeley National Laboratory,

Berkeley, California, USA Jay D Keasling * Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, USA Jay D Keasling * Department of

Bioengineering, University of California, Berkeley, Berkeley, California, USA Jay D Keasling Authors * Mette L Skjoedt View author publications You can also search for this author inPubMed 

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publications You can also search for this author inPubMed Google Scholar * Jie Zhang View author publications You can also search for this author inPubMed Google Scholar * Mette Kristensen

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author inPubMed Google Scholar CONTRIBUTIONS M.L.S., T.S., J.D.K. and M.K.J. conceived this project. M.L.S., T.S. and M.K.J. designed all of the experiments. M.L.S., T.S. and D.A. performed

all flow cytometry analyses. M.L.S., T.S., D.A., B.J.L., J.Z., K.R.K., S.S., T.J.G. and M.E. constructed all strains and plasmids. M.K. and K.R.K. performed all analytical measurements, and

M.K.J. performed the RNA-seq experiment. M.L.S., T.S., M.K.J., I.B., A.S.R. and K.R.K. analyzed the data. M.K.J. wrote the paper. CORRESPONDING AUTHOR Correspondence to Michael K Jensen.

ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Results, Supplementary

Figures 1–7 and Supplementary Tables 1–5. (PDF 2914 kb) SUPPLEMENTARY DATASET 1 RNA-seq gene list. (XLSX 947 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Skjoedt, M., Snoek, T., Kildegaard, K. _et al._ Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast. _Nat Chem Biol_ 12, 951–958 (2016).

https://doi.org/10.1038/nchembio.2177 Download citation * Received: 19 August 2015 * Accepted: 30 June 2016 * Published: 19 September 2016 * Issue Date: November 2016 * DOI:

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