Implementation of a Reductive Route of One-Carbon Assimilation in Escherichia coli through Directed Evolution

ACS Synth Biol. 2018 Sep 21;7(9):2029-2036. doi: 10.1021/acssynbio.8b00167. Epub 2018 Aug 23.

Abstract

Endowing biotechnological platform organisms with new carbon assimilation pathways is a key challenge for industrial biotechnology. Here we report progress toward the construction of formatotrophic Escherichia coli strains. Glycine and serine, universal precursors of one-carbon compounds oxidized during heterotrophic growth, are produced from formate and CO2 through a reductive route. An adaptive evolution strategy was applied to optimize the enzymatic steps of this route in appropriate selection strains. Metabolic labeling experiments with 13C-formate confirm the redirected carbon-flow. These results demonstrate the high plasticity of the central carbon metabolism of E. coli and the applicative potential of directed evolution for implementing synthetic pathways in microorganisms.

Keywords: directed evolution; formate assimilation; glycine cleavage complex; long-term continuous culture; one-carbon metabolism; synthetic metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / analysis
  • Carbon / metabolism*
  • Carbon Dioxide / metabolism
  • Carbon Isotopes / chemistry
  • Chromatography, High Pressure Liquid
  • Directed Molecular Evolution / methods*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Formates / chemistry
  • Formates / metabolism
  • Glutathione / analysis
  • Glutathione / chemistry
  • Serine / metabolism
  • Tandem Mass Spectrometry

Substances

  • Carbon Isotopes
  • Formates
  • formic acid
  • Carbon Dioxide
  • Serine
  • Carbon
  • Carbon-13
  • Glutathione