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Metab Eng. 2014 May;23:175-84. doi: 10.1016/j.ymben.2014.02.008. Epub 2014 Feb 24.

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

Author information

1
Laboratory for Bioinformatics, Graduate School of Systems Biosciences, Kyushu University, 804 Westwing, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
2
Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan.
3
Laboratory for Bioinformatics, Graduate School of Systems Biosciences, Kyushu University, 804 Westwing, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. Electronic address: taizo@brs.kyushu-u.ac.jp.

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.

KEYWORDS:

Metabolic flux redirection; Metabolic toggle switch; Synthetic genetic circuit; Synthetic pathway

PMID:
24576819
DOI:
10.1016/j.ymben.2014.02.008
[Indexed for MEDLINE]

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