Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae

T. C. Williams, N. J H Averesch, G. Winter, M. R. Plan, C. E. Vickers, L. K. Nielsen, J. O. Krömer*

*Corresponding author for this work

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Some of the most productive metabolic engineering strategies involve genetic modifications that cause severe metabolic burden on the host cell. Growth-limiting genetic modifications can be more effective if they are 'switched on' after a population growth phase has been completed. To address this problem we have engineered dynamic regulation using a previously developed synthetic quorum sensing circuit in Saccharomyces cerevisiae. The circuit autonomously triggers gene expression at a high population density, and was linked with an RNA interference module to enable target gene silencing. As a demonstration the circuit was used to control flux through the shikimate pathway for the production of para-hydroxybenzoic acid (PHBA). Dynamic RNA repression allowed gene knock-downs which were identified by elementary flux mode analysis as highly productive but with low biomass formation to be implemented after a population growth phase, resulting in the highest published PHBA titer in yeast (1.1. mM).

Original languageEnglish
Pages (from-to)124-134
Number of pages11
JournalMetabolic Engineering
Volume29
DOIs
Publication statusPublished - 1 May 2015
Externally publishedYes

Keywords

  • Quorum sensing
  • Dynamic regulation
  • Cell-cell communication
  • PHBA
  • Shikimate pathway
  • RNA interference

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