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@ARTICLE{Bartek:15863,
      author       = {Bartek, T. and Blombach, B. and Lang, S. and Eikmanns, B.J.
                      and Wiechert, W. and Oldiges, M. and Nöh, K. and Noack, S.},
      title        = {{C}omparative 13{C}-metabolic flux analysis of pyruvate
                      dehydrogenase complex-deficient {L}-valine-producing
                      {C}orynebacterium glutamicum},
      journal      = {Applied and environmental microbiology},
      volume       = {77},
      issn         = {0099-2240},
      address      = {Washington, DC [u.a.]},
      publisher    = {Soc.},
      reportid     = {PreJuSER-15863},
      pages        = {6644 - 6652},
      year         = {2011},
      note         = {This work was financially supported by the Fachagentur
                      Nachwachsende Rohstoffe (Agency for Renewable Resources) of
                      the BMVEL, German Federal Ministry of Food, Agriculture and
                      Consumer Protection (grant 04NR003/22000304), and by Evonik
                      Degussa GmbH.},
      abstract     = {L-Valine can be formed successfully using C. glutamicum
                      strains missing an active pyruvate dehydrogenase enzyme
                      complex (PDHC). Wild-type C. glutamicum and four
                      PDHC-deficient strains were compared by (13)C metabolic flux
                      analysis, especially focusing on the split ratio between
                      glycolysis and the pentose phosphate pathway (PPP). Compared
                      to the wild type, showing a carbon flux of $69\%$ ± $14\%$
                      through the PPP, a strong increase in the PPP flux was
                      observed in PDHC-deficient strains with a maximum of $113\%$
                      ± $22\%.$ The shift in the split ratio can be explained by
                      an increased demand of NADPH for l-valine formation. In
                      accordance, the introduction of the Escherichia coli
                      transhydrogenase PntAB, catalyzing the reversible conversion
                      of NADH to NADPH, into an L-valine-producing C. glutamicum
                      strain caused the PPP flux to decrease to $57\%$ ± $6\%,$
                      which is below the wild-type split ratio. Hence,
                      transhydrogenase activity offers an alternative perspective
                      for sufficient NADPH supply, which is relevant for most
                      amino acid production systems. Moreover, as demonstrated for
                      L-valine, this bypass leads to a significant increase of
                      product yield due to a concurrent reduction in carbon
                      dioxide formation via the PPP.},
      keywords     = {Carbon Dioxide: metabolism / Carbon Isotopes: metabolism /
                      Corynebacterium glutamicum: genetics / Corynebacterium
                      glutamicum: metabolism / Escherichia coli: enzymology /
                      Escherichia coli: genetics / Escherichia coli Proteins:
                      genetics / Escherichia coli Proteins: metabolism /
                      Glycolysis / NADP Transhydrogenases: genetics / NADP
                      Transhydrogenases: metabolism / Pentose Phosphate Pathway /
                      Pyruvate Dehydrogenase Complex: genetics / Valine:
                      metabolism / Carbon Isotopes (NLM Chemicals) / Escherichia
                      coli Proteins (NLM Chemicals) / Pyruvate Dehydrogenase
                      Complex (NLM Chemicals) / Carbon Dioxide (NLM Chemicals) /
                      Valine (NLM Chemicals) / NADP Transhydrogenases (NLM
                      Chemicals) / pntA protein, E coli (NLM Chemicals) / pntB
                      protein, E coli (NLM Chemicals) / J (WoSType)},
      cin          = {IBT-2},
      ddc          = {570},
      cid          = {I:(DE-Juel1)VDB56},
      pnm          = {Biotechnologie},
      pid          = {G:(DE-Juel1)FUEK410},
      shelfmark    = {Biotechnology $\&$ Applied Microbiology / Microbiology},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:21784914},
      pmc          = {pmc:PMC3187166},
      UT           = {WOS:000294691400040},
      doi          = {10.1128/AEM.00575-11},
      url          = {https://juser.fz-juelich.de/record/15863},
}