Microbial Cell Factories à la Carte : Elimination of Global Regulators Cra and ArcA Generates Metabolic Backgrounds Suitable for the Synthesis of Bioproducts in Escherichia coli

Abstract

Although the effects of many global regulators, especially ArcA and Cra, have been studied in Escherichia coli , the metabolic changes caused by the absence of global regulators have been observed to differ between strains. This scenario complicates the identification of the individual effects of the regulators, which is essential for the design of metabolic engineering strategies. The genome of Escherichia coli BW25113 has been completely sequenced and does not contain additional mutations that could mask or interfere with the effects of the global regulator mutations. The uniform genetic background of the Keio collection mutants enabled the characterization of the physiological consequences of altered carbon and redox fluxes caused by each global regulator deletion, eliminating possible strain-dependent results. As a proof of concept, Δ cra and Δ arcA mutants were subjected to further manipulations to obtain large amounts of succinate and 1,3-PDO, demonstrating that the metabolic backgrounds of the mutants were suitable for the synthesis of bioproducts.