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@ARTICLE{Tiso:878541,
      author       = {Tiso, Till and Ihling, Nina and Kubicki, Sonja and Biselli,
                      Andreas and Schonhoff, Andreas and Bator, Isabel and Thies,
                      Stephan and Karmainski, Tobias and Kruth, Sebastian and
                      Willenbrink, Anna-Lena and Loeschcke, Anita and Zapp, Petra
                      and Jupke, Andreas and Jaeger, Karl-Erich and Büchs, Jochen
                      and Blank, Lars M.},
      title        = {{I}ntegration of genetic and process engineering for
                      optimized rhamnolipid production using pseudomonas putida},
      journal      = {Frontiers in Bioengineering and Biotechnology},
      volume       = {8},
      issn         = {2296-4185},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {FZJ-2020-02900},
      pages        = {976},
      year         = {2020},
      abstract     = {Rhamnolipids are biosurfactants produced by microorganisms
                      with the potential to replace synthetic compounds with
                      petrochemical origin. To promote industrial use of
                      rhamnolipids, recombinant rhamnolipid production from sugars
                      needs to be intensified. Since this remains challenging, the
                      aim of the presented research is to utilize a
                      multidisciplinary approach to take a step toward developing
                      a sustainable rhamnolipid production process. Here, we
                      developed expression cassettes for stable integration of the
                      rhamnolipid biosynthesis genes into the genome outperformed
                      plasmid-based expression systems. Furthermore, the genetic
                      stability of the production strain was improved by using an
                      inducible promoter. To enhance rhamnolipid synthesis,
                      energy- and/or carbon-consuming traits were removed: mutants
                      negative for the synthesis of the flagellar machinery or the
                      storage polymer PHA showed increased production by $50\%.$
                      Variation of time of induction resulted in an $18\%$
                      increase in titers. A scale-up from shake flasks was carried
                      out using a 1-L bioreactor. By recycling of the foam,
                      biomass loss could be minimized and a rhamnolipid titer of
                      up to 1.5 g/L was achieved without using mechanical foam
                      destroyers or antifoaming agents. Subsequent liquid–liquid
                      extraction was optimized by using a suitable minimal medium
                      during fermentation to reduce undesired interphase
                      formation. A technical-scale production process was designed
                      and evaluated by a life-cycle assessment (LCA). Different
                      process chains and their specific environmental impact were
                      examined. It was found that next to biomass supply, the
                      fermentation had the biggest environmental impact. The
                      present work underlines the need for multidisciplinary
                      approaches to address the challenges associated with
                      achieving sustainable production of microbial secondary
                      metabolites. The results are discussed in the context of the
                      challenges of microbial biosurfactant production using
                      hydrophilic substrates on an industrial scale.},
      cin          = {IEK-STE / IMET / IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IEK-STE-20101013 / I:(DE-Juel1)IMET-20090612 /
                      I:(DE-Juel1)IBG-1-20101118},
      pnm          = {153 - Assessment of Energy Systems – Addressing Issues of
                      Energy Efficiency and Energy Security (POF3-153) / BioSC -
                      Bioeconomy Science Center (BioSC) / 581 - Biotechnology
                      (POF3-581)},
      pid          = {G:(DE-HGF)POF3-153 / G:(DE-Juel1)BioSC /
                      G:(DE-HGF)POF3-581},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32974309},
      UT           = {WOS:000567817700001},
      doi          = {10.3389/fbioe.2020.00976},
      url          = {https://juser.fz-juelich.de/record/878541},
}