Reconstruction of a metabolic regulatory network in Escherichia coli for purposeful switching from cell growth mode to production mode in direct GABA fermentation from glucose

Yuki Soma, Yuri Fujiwara, Takuya Nakagawa, Keigo Tsuruno, Taizo Hanai

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering. The GABA production mode was achieved by multiple strategies such as conditional interruption of the TCA and glyoxylate cycles, engineering of GABA production pathway including a bypass for precursor metabolite supply, and upregulation of GABA transporter. As a result, we achieved 3-fold improvement in total GABA production titer and yield (4.8 g/L, 49.2% (mol/mol glucose)) in batch fermentation compared to the case without metabolic state switching (1.6 g/L, 16.4% (mol/mol glucose)). This study reports the highest GABA production performance among previous reports on GABA fermentation from glucose using engineered E. coli.

元の言語英語
ページ(範囲)54-63
ページ数10
ジャーナルMetabolic Engineering
43
DOI
出版物ステータス出版済み - 9 1 2017

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Cell growth
Metabolic Networks and Pathways
Fermentation
gamma-Aminobutyric Acid
Escherichia coli
Glucose
Growth
Productivity
Food additives
Bioconversion
Biodegradable Plastics
Metabolites
GABA Plasma Membrane Transport Proteins
Polyamides
Aminobutyrates
Food Additives
Functional Food
Nylons
Monomers
Plastics

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

これを引用

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abstract = "γ-aminobutyric acid (GABA) is a drug and functional food additive and is used as a monomer for producing the biodegradable plastic, polyamide 4. Recently, direct GABA fermentation from glucose has been developed as an alternative to glutamate-based whole cell bioconversion. Although total productivity in fermentation is determined by the specific productivity and cell amount responsible for GABA production, the optimal metabolic state for GABA production conflicts with that for bacterial cell growth. Herein, we demonstrated metabolic state switching from the cell growth mode based on the metabolic pathways of the wild type strain to a GABA production mode based on a synthetic metabolic pathway in Escherichia coli through rewriting of the metabolic regulatory network and pathway engineering. The GABA production mode was achieved by multiple strategies such as conditional interruption of the TCA and glyoxylate cycles, engineering of GABA production pathway including a bypass for precursor metabolite supply, and upregulation of GABA transporter. As a result, we achieved 3-fold improvement in total GABA production titer and yield (4.8 g/L, 49.2{\%} (mol/mol glucose)) in batch fermentation compared to the case without metabolic state switching (1.6 g/L, 16.4{\%} (mol/mol glucose)). This study reports the highest GABA production performance among previous reports on GABA fermentation from glucose using engineered E. coli.",
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AU - Tsuruno, Keigo

AU - Hanai, Taizo

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