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@ARTICLE{Jansen:891597,
      author       = {Jansen, Roman and Morschett, Holger and Hasenklever, Dennis
                      and Moch, Matthias and Wiechert, Wolfgang and Oldiges,
                      Marco},
      title        = {{M}icrobioreactor‐assisted cultivation workflows for
                      time‐efficient phenotyping of protein producing
                      {A}spergillus niger in batch and fed‐batch mode},
      journal      = {Biotechnology progress},
      volume       = {37},
      number       = {4},
      issn         = {1520-6033},
      address      = {Malden, MA},
      publisher    = {Wiley},
      reportid     = {FZJ-2021-01608},
      pages        = {e3144},
      year         = {2021},
      abstract     = {In recent years, many fungal genomes have become publicly
                      available. In combination with novel gene editing tools,
                      this allows for accelerated strain construction, making
                      filamentous fungi even more interesting for the production
                      of valuable products. However, besides their extraordinary
                      production and secretion capacities, fungi most often
                      exhibit challenging morphologies, which need to be screened
                      for the best operational window. Thereby, combining genetic
                      diversity with various environmental parameters results in a
                      large parameter space, creating a strong demand for
                      time‐efficient phenotyping technologies. Microbioreactor
                      systems, which have been well established for bacterial
                      organisms, enable an increased cultivation throughput via
                      parallelization and miniaturization, as well as enhanced
                      process insight via non‐invasive online monitoring.
                      Nevertheless, only few reports about microtiter plate
                      cultivation for filamentous fungi in general and even less
                      with online monitoring exist in literature. Moreover,
                      screening under batch conditions in microscale, when a
                      fed‐batch process is performed in large‐scale might even
                      lead to the wrong identification of optimized parameters.
                      Therefore, in this study a novel workflow for Aspergillus
                      niger was developed, allowing for up to 48 parallel
                      microbioreactor cultivations in batch as well as fed‐batch
                      mode. This workflow was validated against lab‐scale
                      bioreactor cultivations to proof scalability. With the
                      optimized cultivation protocol, three different
                      micro‐scale fed‐batch strategies were tested to identify
                      the best protein production conditions for intracellular
                      model product GFP. Subsequently, the best feeding strategy
                      was again validated in a lab‐scale bioreactor.},
      cin          = {IBG-1},
      ddc          = {660},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2172 - Utilization of renewable carbon and energy sources
                      and engineering of ecosystem functions (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2172},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33745237},
      UT           = {WOS:000634853000001},
      doi          = {10.1002/btpr.3144},
      url          = {https://juser.fz-juelich.de/record/891597},
}