Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch

Yuki Soma, Keigo Tsuruno, Masaru Wada, Atsushi Yokota, Taizo Hanai

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

Abstract

Overexpression of genes in production pathways and permanent knockout of genes in competing pathways are often employed to improve production titer and yield in metabolic engineering. However, the deletion of a pathway responsible for growth and cell maintenance has not previously been employed, even if its competition with the production pathway is obvious. In order to optimize intracellular metabolism at each fermentation phase for bacterial growth and production, a methodology employing conditional knockout is required. We constructed a metabolic toggle switch in Escherichia coli as a novel conditional knockout approach and applied it to isopropanol production. The resulting redirection of excess carbon flux caused by interruption of the TCA cycle via switching gltA OFF improved isopropanol production titer and yield up to 3.7 and 3.1 times, respectively. This approach is a useful tool to redirect carbon flux responsible for bacterial growth and/or cell maintenance toward a synthetic production pathway.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalMetabolic Engineering
Volume23
DOIs
Publication statusPublished - May 2014

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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