% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Pooth:866100,
      author       = {Pooth, Viola and Gaalen, Kathrin and Trenkamp, Sandra and
                      Wiechert, Wolfgang and Oldiges, Marco},
      title        = {{C}omprehensive analysis of metabolic sensitivity of
                      1,4‐butanediol producing {E}scherichia coli toward
                      substrate and oxygen availability},
      journal      = {Biotechnology progress},
      volume       = {36},
      number       = {1},
      issn         = {1520-6033},
      address      = {Malden, MA},
      publisher    = {Wiley},
      reportid     = {FZJ-2019-05319},
      pages        = {e2917},
      year         = {2020},
      abstract     = {Nowadays, chemical production of 1,4‐butanediol is
                      supplemented by biotechnological processes using a
                      genetically modified Escherichia coli strain, which is an
                      industrial showcase of successful application of metabolic
                      engineering. However, large scale bioprocess performance can
                      be affected by presence of physical and chemical gradients
                      in bioreactors which are a consequence of imperfect mixing
                      and limited oxygen transfer. Hence, upscaling comes along
                      with local and time dependent fluctuations of cultivation
                      conditions. This study emphasizes on scale‐up related
                      effects of microbial 1,4‐butanediol production by
                      comprehensive bioprocess characterization in lab scale. Due
                      to metabolic network constraints 1,4‐butanediol formation
                      takes place under oxygen limited microaerobic conditions,
                      which can be hardly realized in large scale bioreactor. The
                      purpose of this study was to assess the extent to which
                      substrate and oxygen availability influence the
                      productivity. It was found, that the substrate specific
                      product yield and the production rate are higher under
                      substrate excess than under substrate limitation.
                      Furthermore, the level of oxygen supply within microaerobic
                      conditions revealed strong effects on product and
                      by‐product formation. Under strong oxygen deprivation
                      nearly $30\%$ of the consumed carbon is converted into
                      1,4‐butanediol, whereas an increase in oxygen supply
                      results in 1,4‐butanediol reduction of $77\%.$ Strikingly,
                      increasing oxygen availability leads to strong increase of
                      main by‐product acetate as well as doubled carbon dioxide
                      formation. The study provides clear evidence that scale‐up
                      of microaerobic bioprocesses constitute a substantial
                      challenge. Although oxygen is strictly required for product
                      formation, the data give clear evidence that terms of
                      anaerobic and especially aerobic conditions strongly
                      interfere with 1,4‐butanediol production.},
      cin          = {IBG-1},
      ddc          = {660},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {581 - Biotechnology (POF3-581)},
      pid          = {G:(DE-HGF)POF3-581},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31587523},
      UT           = {WOS:000493578100001},
      doi          = {10.1002/btpr.2917},
      url          = {https://juser.fz-juelich.de/record/866100},
}