RT Journal Article SR Electronic T1 An orthogonal and pH-tunable sensor-selector for muconic acid biosynthesis in yeast JF bioRxiv FD Cold Spring Harbor Laboratory SP 229922 DO 10.1101/229922 A1 Tim Snoek A1 David Romero-Suarez A1 Jie Zhang A1 Mette L. Skjoedt A1 Suresh Sudarsan A1 Michael K. Jensen A1 Jay D. Keasling YR 2017 UL http://biorxiv.org/content/early/2017/12/06/229922.abstract AB 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.