Synthetic Bistability and Differentiation in Yeast

ACS Synth Biol. 2019 May 17;8(5):929-936. doi: 10.1021/acssynbio.8b00524. Epub 2019 May 1.


Engineered systems that control cellular differentiation and pattern formation are essential for applications like tissue engineering, biomaterial fabrication, and synthetic ecosystems. Synthetic circuits that can take on multiple states have been made to engineer multicellular systems. However, how to use these states to drive interesting cellular behavior remains challenging. Here, we present a cellular differentiation program involving a novel synthetic bistable switch coupled to an antibiotic resistance gene that affects growth in yeast ( S. cerevisiae). The switch is composed of a positive feedback loop involving a novel transcription factor and can be switched ON and OFF via two different transient inducer inputs. By further coupling the bistable switch with an antibiotic resistance gene, we obtained a growth differentiation circuit, where yeast cells can be switched to stable HIGH or LOW growth rate states via transient inducer inputs. This work demonstrates a rationally designed and experimentally validated cellular differentiation behavior in yeast.

Keywords: antibiotic resistance; bistability; cellular differentiation; growth control; yeast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Drug Resistance, Microbial / genetics*
  • Indoleacetic Acids / pharmacology
  • Models, Biological
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism
  • Synthetic Biology / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Indoleacetic Acids
  • Transcription Factors