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

Williams, T. C., Averesch, N. J. H., Winter, G., Plan, M. R., Vickers, C. E., Nielsen, L. K. and Kromer, J. O. (2015) Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae. Metabolic Engineering, 29 124-134. doi:10.1016/j.ymben.2015.03.008


Author Williams, T. C.
Averesch, N. J. H.
Winter, G.
Plan, M. R.
Vickers, C. E.
Nielsen, L. K.
Kromer, J. O.
Title Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae
Formatted title
Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae
Journal name Metabolic Engineering   Check publisher's open access policy
ISSN 1096-7184
1096-7176
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.ymben.2015.03.008
Open Access Status
Volume 29
Start page 124
End page 134
Total pages 11
Place of publication Waltham, MA United States
Publisher Academic Press
Collection year 2016
Language eng
Formatted 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).
Keyword Quorum sensing
Dynamic regulation
Cell-cell communication
PHBA
Shikimate pathway
RNA interference
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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