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@ARTICLE{Sudar:890996,
      author       = {Sudar, Martina and Česnik, Morana and Clapés, Pere and
                      Pohl, Martina and Vasić-Rački, Đurđa and Findrik
                      Blažević, Zvjezdana},
      title        = {{A} cascade reaction for the synthesis of d-fagomine
                      precursor revisited: {K}inetic insight and understanding of
                      the system},
      journal      = {New biotechnology},
      volume       = {63},
      issn         = {1871-6784},
      address      = {New York, NY [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2021-01303},
      pages        = {19 - 28},
      year         = {2021},
      abstract     = {The synthesis of aldol adduct
                      (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose,
                      a precursor of the interesting dietary supplement,
                      iminosugar d-fagomine, was studied in a cascade reaction
                      with three enzymes starting from Cbz-N-3-aminopropanol. This
                      system was studied previously using a statistical
                      optimization method which enabled a 79 $\%$ yield of the
                      aldol adduct with a 10 $\%$ yield of the undesired amino
                      acid by-product. Here, a kinetic model of the cascade,
                      including enzyme operational stability decay rate and the
                      undesired overoxidation of the intermediate product, was
                      developed. The validated model was instrumental in the
                      optimization of the cascade reaction in the batch reactor.
                      Simulations were carried out to determine the variables with
                      the most significant impact on substrate conversion and
                      product yield. As a result, process conditions were found
                      that provided the aldol adduct in 92 $\%$ yield with only
                      0.7 $\%$ yield of the amino acid in a one-pot one-step
                      reaction. Additionally, compared to previous work, this
                      improved process outcome was achieved at lower
                      concentrations of two enzymes used in the reaction. With
                      this study the advantages are demonstrated of a modelling
                      approach in developing complex biocatalytical processes.
                      Mathematical models enable better understanding of the
                      interactions of variables in the investigated system, reduce
                      cost, experimental efforts in the lab and time necessary to
                      obtain results since the simulations are carried out in
                      silico.},
      cin          = {IBG-1},
      ddc          = {540},
      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       = {33640482},
      UT           = {WOS:000637216500003},
      doi          = {10.1016/j.nbt.2021.02.004},
      url          = {https://juser.fz-juelich.de/record/890996},
}