%0 Journal Article %A Tim Snoek %A David Romero-Suarez %A Jie Zhang %A Mette L. Skjoedt %A Suresh Sudarsan %A Michael K. Jensen %A Jay D. Keasling %T An orthogonal and pH-tunable sensor-selector for muconic acid biosynthesis in yeast %D 2017 %R 10.1101/229922 %J bioRxiv %P 229922 %X Microbes offer enormous potential for production of industrially relevant chemicals and therapeutics, yet the rapid identification of high-producing microbes from large genetic libraries is a major bottleneck in modern cell factory development. Here, we develop and apply a synthetic selection system in Saccharomyces cerevisiae that couples the concentration of muconic acid, a plastic precursor, to cell fitness by using the prokaryotic transcriptional regulator BenM driving an antibiotic resistance gene. We show the sensor-selector does not affect production, and find that tuning pH of the cultivation medium limits the rise of non-producing cheaters. We apply the sensor-selector to selectively enrich for best-producing variants out of a large library of muconic acid production strains, and identify an isolate that produced more than 2 g/L muconic acid in a bioreactor. We expect that this sensor-selector can aid the development of other synthetic selection systems based on allosteric transcription factors. %U https://www.biorxiv.org/content/biorxiv/early/2017/12/06/229922.full.pdf