期刊
METABOLIC ENGINEERING
卷 29, 期 -, 页码 124-134出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2015.03.008
关键词
Quorum sensing; Dynamic regulation; Cell-cell communication; PHBA; Shikimate pathway; RNA interference
资金
- Australian Postgraduate Award
- AIBN Top-Up Scholarship
- Australian Research Council [DE120101549]
- Queensland Government, Australia Smart Futures fellowship
- Australian Research Council [DE120101549] Funding Source: Australian Research Council
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 Sacchuromyces 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). (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
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