Efficient production of gamma-aminobutyric acid using Escherichia coli by co-localization of glutamate synthase, glutamate decarboxylase, and GABA transporter

J Ind Microbiol Biotechnol. 2016 Jan;43(1):79-86. doi: 10.1007/s10295-015-1712-8. Epub 2015 Nov 30.

Abstract

Gamma-aminobutyric acid (GABA) is an important bio-product, which is used in pharmaceutical formulations, nutritional supplements, and biopolymer monomer. The traditional GABA process involves the decarboxylation of glutamate. However, the direct production of GABA from glucose is a more efficient process. To construct the recombinant strains of Escherichia coli, a novel synthetic scaffold was introduced. By carrying out the co-localization of glutamate synthase, glutamate decarboxylase, and GABA transporter, we redirected the TCA cycle flux to GABA pathway. The genetically engineered E. coli strain produced 1.08 g/L of GABA from 10 g/L of initial glucose. Thus, with the introduction of a synthetic scaffold, we increased GABA production by 2.2-fold. The final GABA concentration was increased by 21.8% by inactivating competing pathways.

Keywords: Co-localization; GABA; Protein scaffold; Synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosynthetic Pathways
  • Citric Acid Cycle
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • Glucose / metabolism*
  • Glutamate Decarboxylase / metabolism*
  • Glutamate Synthase / metabolism*
  • Ligands
  • Metabolic Engineering*
  • Protein Binding
  • Protein Transport
  • Synthetic Biology
  • gamma-Aminobutyric Acid / biosynthesis*

Substances

  • GABA Plasma Membrane Transport Proteins
  • Ligands
  • gamma-Aminobutyric Acid
  • Glutamate Synthase
  • Glutamate Decarboxylase
  • Glucose