Genome-wide analysis of redox reactions reveals metabolic engineering targets for d-lactate overproduction in Escherichia coli

Hyun Ju Kim, Bo Kyeng Hou, Sung Gun Lee, Joong Su Kim, Dong Woo Lee, Sang Jun Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Most current metabolic engineering applications rely on the inactivation of unwanted reactions and the amplification of product-oriented reactions. All of the biochemical reactions involved with cellular metabolism are tightly coordinated with the electron flow, which depends on the cellular energy status. Thus, the cellular metabolic flux can be controlled either by modulation of the electron flow or the regulation of redox reactions. This study analyzed the genome-wide anaerobic fermentation products of 472 Escherichia coli single gene knockouts, which comprised mainly of dehydrogenases, oxidoreductases, and redox-related proteins. Many metabolic pathways that were located far from anaerobic mixed-acid fermentation significantly affected the profiles of lactic acid, succinic acid, acetic acid, formic acid, and ethanol. Unexpectedly, d-lactate overproduction was determined by a single gene deletion in dehydrogenases (e.g., guaB, pyrD, and serA) involved with nucleotide and amino acid metabolism. Furthermore, the combined knockouts of guaB, pyrD, serA, fnr, arcA, or arcB genes, which are involved with anaerobic transcription regulation, enhanced d-lactate overproduction. These results suggest that the anaerobic fermentation profiles of E. coli can be tuned via the disruption of peripheral dehydrogenases in anaerobic conditions.

Original languageEnglish
Pages (from-to)44-52
Number of pages9
JournalMetabolic Engineering
Volume18
DOIs
Publication statusPublished - 2013 Jul 1

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Metabolic engineering
Metabolic Engineering
Redox reactions
Escherichia coli
Oxidation-Reduction
Lactic Acid
Oxidoreductases
Genes
Genome
Fermentation
formic acid
Metabolism
Electrons
Gene Knockout Techniques
Acids
Formic acid
Gene Deletion
Succinic Acid
Transcription
Lactic acid

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Kim, Hyun Ju ; Hou, Bo Kyeng ; Lee, Sung Gun ; Kim, Joong Su ; Lee, Dong Woo ; Lee, Sang Jun. / Genome-wide analysis of redox reactions reveals metabolic engineering targets for d-lactate overproduction in Escherichia coli. In: Metabolic Engineering. 2013 ; Vol. 18. pp. 44-52.
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Genome-wide analysis of redox reactions reveals metabolic engineering targets for d-lactate overproduction in Escherichia coli. / Kim, Hyun Ju; Hou, Bo Kyeng; Lee, Sung Gun; Kim, Joong Su; Lee, Dong Woo; Lee, Sang Jun.

In: Metabolic Engineering, Vol. 18, 01.07.2013, p. 44-52.

Research output: Contribution to journalArticle

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