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https://hdl.handle.net/1959.11/20479
Title: | Quorum-sensing linked RNA interference for dynamic metabolic pathway control in 'Saccharomyces cerevisiae' | Contributor(s): | Williams, T C (author); Averesch, N J H (author); Winter, Gal (author) ; Plan, M R (author); Vickers, C E (author); Nielsen, L K (author); Kromer, J O (author) | Publication Date: | 2015 | DOI: | 10.1016/j.ymben.2015.03.008 | Handle Link: | https://hdl.handle.net/1959.11/20479 | 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). | Publication Type: | Journal Article | Source of Publication: | Metabolic Engineering, v.29, p. 124-134 | Publisher: | Academic Press | Place of Publication: | United States of America | ISSN: | 1096-7184 1096-7176 |
Fields of Research (FoR) 2008: | 060113 Synthetic Biology | Fields of Research (FoR) 2020: | 310113 Synthetic biology | Socio-Economic Objective (SEO) 2008: | 970106 Expanding Knowledge in the Biological Sciences | Socio-Economic Objective (SEO) 2020: | 280102 Expanding knowledge in the biological sciences | Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article |
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