A Systems Biology Approach Uncovers Cellular Strategies Used by Methylobacterium extorquens AM1 During the Switch from Multi- to Single-carbon growth

Elizabeth Skovran, Gregory J. Crowther, Xiaofeng Guo, Song Yang, Mary E. Lidstrom

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. Methodology/Principal Findings: This study focused on the mechanisms of metabolic adaptation occurring during the transition from succinate growth (predicted to be energy-limited) to methanol growth (predicted to be reducing-powerlimited), analyzing changes in carbon flux, gene expression, metabolites and enzymatic activities over time. Initially, cells experienced metabolic imbalance with excretion of metabolites, changes in nucleotide levels and cessation of cell growth. Though assimilatory pathways were induced rapidly, a transient block in carbon flow to biomass synthesis occurred, and enzymatic assays suggested methylene tetrahydrofolate dehydrogenase as one control point. This "downstream priming" mechanism ensures that significant carbon flux through these pathways does not occur until they are fully induced, precluding the buildup of toxic intermediates. Most metabolites that are required for growth on both carbon sources did not change significantly, even though transcripts and enzymatic activities required for their production changed radically, underscoring the concept of metabolic setpoints. Conclusions/Significance: This multi-level approach has resulted in new insights into the metabolic strategies carried out to effect this shift between two dramatically different modes of growth and identified a number of potential flux control and regulatory check points as a further step toward understanding metabolic adaptation and the cellular strategies employed to maintain metabolic setpoints.

Original languageEnglish (US)
Article numbere14091
JournalPLoS One
Volume5
Issue number11
DOIs
StatePublished - 2010

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Methylobacterium extorquens
Systems Biology
Carbon
Switches
Biological Sciences
carbon
Growth
Metabolites
Carbon Cycle
Fluxes
metabolites
Metabolic Networks and Pathways
dihydrofolate reductase
Tetrahydrofolate Dehydrogenase
Poisons
Cell growth
Succinic Acid
succinic acid
Gene expression
Enzyme Assays

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A Systems Biology Approach Uncovers Cellular Strategies Used by Methylobacterium extorquens AM1 During the Switch from Multi- to Single-carbon growth. / Skovran, Elizabeth; Crowther, Gregory J.; Guo, Xiaofeng; Yang, Song; Lidstrom, Mary E.

In: PLoS One, Vol. 5, No. 11, e14091, 2010.

Research output: Contribution to journalArticle

Skovran, Elizabeth ; Crowther, Gregory J. ; Guo, Xiaofeng ; Yang, Song ; Lidstrom, Mary E. / A Systems Biology Approach Uncovers Cellular Strategies Used by Methylobacterium extorquens AM1 During the Switch from Multi- to Single-carbon growth. In: PLoS One. 2010 ; Vol. 5, No. 11.
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