title: Quorum-sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae.
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 (1.1mM).
authors: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: T C
authors: TC
authors: Williams
authors: Centre for Microbial Electrosynthesis (CEMES), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: N J H
authors: NJH
authors: Averesch
authors: Centre for Microbial Electrosynthesis (CEMES), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: G
authors: G
authors: Winter
authors: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St. Lucia, QLD 4072, Australia; Metabolomics Australia (Queensland Node), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: M R
authors: MR
authors: Plan
authors: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: C E
authors: CE
authors: Vickers
authors: Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St. Lucia, QLD 4072, Australia.
authors: L K
authors: LK
authors: Nielsen
authors: Centre for Microbial Electrosynthesis (CEMES), The University of Queensland, St. Lucia, QLD 4072, Australia; Advanced Water Management Centre (AWMC), The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: j.kromer@uq.edu.au.
authors: J O
authors: JO
authors: Krömer
mesh_terms: D015966:Gene Expression Regulation, Fungal; D010226:Parabens / Q000378:metabolism*; D053038:Quorum Sensing / Q000235:genetics*; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012765:Shikimic Acid / Q000378:metabolism*
chemical_list: D010226:Parabens; D012765:Shikimic Acid; C038193:4-hydroxybenzoic acid
keywords: Cell–cell communication; Dynamic regulation; PHBA; Quorum sensing; RNA interference; Shikimate pathway