Escherichia coli redox mutants as microbial cell factories for the synthesis of reduced biochemicals

Jimena A. Ruiz, Alejandra De Almeida, Manuel S. Godoy, Mariela P. Mezzina, Gonzalo N. Bidart, Beatriz S. Méndez, M. Julia Pettinari, Pablo Ivan Nikel

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Abstract

Bioprocesses conducted under conditions with restricted O2 supply are increasingly exploited for the synthesis of reduced biochemicals using different biocatalysts. The model facultative aerobe Escherichia coli, the microbial cell factory par excellence, has elaborate sensing and signal transduction mechanisms that respond to the availability of electron acceptors and alternative carbon sources in the surrounding environment. In particular, the ArcBA and CreBC two-component signal transduction systems are largely responsible for the metabolic regulation of redox control in response to O2 availability and carbon source utilization, respectively. Significant advances in the understanding of the biochemical, genetic, and physiological duties of these regulatory systems have been achieved in recent years. This situation allowed to rationally-design novel engineering approaches that ensure optimal carbon and energy flows within central metabolism, as well as to manipulate redox homeostasis, in order to optimize the production of industrially-relevant metabolites. In particular, metabolic flux analysis provided new clues to understand the metabolic regulation mediated by the ArcBA and CreBC systems. Genetic manipulation of these regulators proved useful for designing microbial cells factories tailored for the synthesis of reduced biochemicals with added value, such as poly(3-hydroxybutyrate), under conditions with restricted O2 supply. This network-wide strategy is in contrast with traditional metabolic engineering approaches, that entail direct modification of the pathway(s) at stake, and opens new avenues for the targeted modulation of central catabolic pathways at the transcriptional level. 
Original languageEnglish
Article numbere201210019
JournalComputational and Structural Biotechnology Journal
Volume3
Issue number4
Number of pages10
ISSN2001-0370
DOIs
Publication statusPublished - 2012
Externally publishedYes

Bibliographical note

© 2012 Bernstein and Carlson.

Keywords

  • ArcBA
  • CreBC
  • Escherichia coli
  • Metabolic flux analysis
  • Polyhydroxyalkanoates
  • Redox homeostasis
  • Reduced biochemicals

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