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Nat Commun. 2014;5:3233. doi: 10.1038/ncomms4233.

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol.

Author information

  • 11] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-8520, Japan [3] Institute of Bioproduct Development and Department of Bioprocess Engineering, Universiti Teknologi Malaysia, Johor 81310, Malaysia.
  • 21] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-8520, Japan [3].
  • 31] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-8520, Japan [3] PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
  • 41] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-8520, Japan.
  • 5Department of Electronic Science, Xiamen University, Xiamen 361005, China.
  • 61] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan [2] Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-8520, Japan [3] Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan.
  • 7Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412, USA.

Abstract

Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.

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