A Glucose-Sensing Toggle Switch for Autonomous, High Productivity Genetic Control

William Bothfeld, Grace Kapov, Keith E.J. Tyo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Many biosynthetic strategies are coupled to growth, which is inherently limiting, as (1) excess feedstock (e.g., sugar) may be converted to biomass, instead of product, (2) essential genes must be maintained, and (3) growth toxicity must be managed. A decoupled growth and production phase strategy could avoid these issues. We have developed a toggle switch that uses glucose sensing to enable this two-phase strategy. Temporary glucose starvation precisely and autonomously activates product pathway expression in rich or minimal media, obviating the requirement for expensive inducers. The switch remains stably in the new state even after reintroduction of glucose. In the context of polyhydroxybutyrate (PHB) biosynthesis, our system enables shorter growth phases and comparable titers to a constitutively expressing PHB strain. This two-phase production strategy, and specifically the glucose toggle switch, should be broadly useful to initiate many types of genetic program for metabolic engineering applications.

Original languageEnglish (US)
Pages (from-to)1296-1304
Number of pages9
JournalACS synthetic biology
Volume6
Issue number7
DOIs
StatePublished - Jul 21 2017

Keywords

  • PHB production
  • genetic toggle switch
  • glucose sensing
  • metabolic engineering

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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