Engineering synergetic CO2-fixing pathways for malate production

Metab Eng. 2018 May:47:496-504. doi: 10.1016/j.ymben.2018.05.007. Epub 2018 May 16.

Abstract

Increasing the microbial CO2-fixing efficiency often requires supplying sufficient ATP and redirecting carbon flux for the production of metabolites. However, addressing these two issues concurrently remains a challenge. Here, we present a combinational strategy based on a synergetic CO2-fixing pathway that combines an ATP-generating carboxylation reaction in the central metabolic pathway with the ATP-consuming RuBisCO shunt in the carbon fixation pathway. This strategy provides enough ATP to improve the efficiency of CO2 fixation and simultaneously rewires the CO2-fixing pathway to the central metabolic pathway for the biosynthesis of chemicals. We demonstrate the application of this strategy by increasing the CO2-fixing rate and malate production in the autotroph Synechococcus elongatus by 110% and to 260 μM respectively, as well as increasing these two factors in the heterotrophic CO2-fixing Escherichia coli by 870% and to 387 mM respectively.

Keywords: ATP balance; CO(2) fixation; Malate production; Pathway engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbon Dioxide / metabolism*
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Malates / metabolism*
  • Metabolic Engineering*
  • Microorganisms, Genetically-Modified* / genetics
  • Microorganisms, Genetically-Modified* / metabolism
  • Synechococcus / genetics

Substances

  • Bacterial Proteins
  • Malates
  • Carbon Dioxide
  • malic acid