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@ARTICLE{Kappelmann:890651,
      author       = {Kappelmann, Jannick and Klein, Bianca and Papenfuß,
                      Mathias and Lange, Julian and Blombach, Bastian and Takors,
                      Ralf and Wiechert, Wolfgang and Polen, Tino and Noack,
                      Stephan},
      title        = {{C}omprehensive {A}nalysis of {C}. glutamicum {A}naplerotic
                      {D}eletion {M}utants {U}nder {D}efined d-{G}lucose
                      {C}onditions},
      journal      = {Frontiers in Bioengineering and Biotechnology},
      volume       = {8},
      issn         = {2296-4185},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {FZJ-2021-01099},
      pages        = {602936},
      year         = {2021},
      abstract     = {Wild-type C. glutamicum ATCC 13032 is known to possess two
                      enzymes with anaplerotic (C4-directed) carboxylation
                      activity, namely phosphoenolpyruvate carboxylase (PEPCx) and
                      pyruvate carboxylase (PCx). On the other hand, C3-directed
                      decarboxylation can be catalyzed by the three enzymes
                      phosphoenolpyruvate carboxykinase (PEPCk), oxaloacetate
                      decarboxylase (ODx), and malic enzyme (ME). The resulting
                      high metabolic flexibility at the anaplerotic node
                      compromises the unambigous determination of its carbon and
                      energy flux in C. glutamicum wild type. To circumvent this
                      problem we performed a comprehensive analysis of selected
                      single or double deletion mutants in the anaplerosis of
                      wild-type C. glutamicum under defined D-glucose conditions.
                      By applying well-controlled lab-scale bioreactor experiments
                      in combination with untargeted proteomics, quantitative
                      metabolomics and whole-genome sequencing hitherto unknown,
                      and sometimes counter-intuitive, genotype-phenotype
                      relationships in these mutants could be unraveled. In
                      comparison to the wild type the four mutants C. glutamiucm
                      Δpyc, C. glutamiucm Δpyc Δodx, C. glutamiucm Δppc Δpyc,
                      and C. glutamiucm Δpck showed lowered specific growth rates
                      and D-glucose uptake rates, underlining the importance of
                      PCx and PEPCk activity for a balanced carbon and energy flux
                      at the anaplerotic node. Most interestingly, the strain C.
                      glutamiucm Δppc Δpyc could be evolved to grow on D-glucose
                      as the only source of carbon and energy, whereas this
                      combination was previously considered lethal. The prevented
                      anaplerotic carboxylation activity of PEPCx and PCx was
                      found in the evolved strain to be compensated by an
                      up-regulation of the glyoxylate shunt, potentially in
                      combination with the 2-methylcitrate cycl},
      cin          = {IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2171 - Biological and environmental resources for
                      sustainable use (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2171},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {33553115},
      UT           = {WOS:000614085700001},
      doi          = {10.3389/fbioe.2020.602936},
      url          = {https://juser.fz-juelich.de/record/890651},
}