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@ARTICLE{Ramp:1007355,
      author       = {Ramp, Paul and Mack, Christina and Wirtz, Astrid and Bott,
                      Michael},
      title        = {{A}lternative routes for production of the drug candidate
                      d-chiro-inositol with {C}orynebacterium glutamicum using
                      endogenous or promiscuous plant enzymes},
      journal      = {Metabolic engineering},
      volume       = {78},
      issn         = {1096-7176},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2023-02024},
      pages        = {1 - 10},
      year         = {2023},
      note         = {Biotechnologie 1},
      abstract     = {d-chiro-Inositol (DCI) is a promising drug candidate for
                      treating insulin resistance and associated diseases such as
                      type 2 diabetes or polycystic ovary syndrome. In this study,
                      we developed two production processes for DCI using
                      Corynebacterium glutamicum as host. In the first process,
                      myo-inositol (MI) is oxidized to 2-keto-myo-inositol (2KMI)
                      by the inositol dehydrogenase (IDH) IolG and then isomerized
                      to 1-keto-d-chiro-inositol (1KDCI) by the isomerases Cg0212
                      or Cg2312, both of which were identified in this work. 1KDCI
                      is then reduced to DCI by IolG. Overproduction of IolG and
                      Cg0212 in a chassis strain unable to degrade inositols
                      allowed the production of 1.1 g/L DCI from 10 g/L MI. As
                      both reactions involved are reversible, only a partial
                      conversion of MI to DCI can be achieved. To enable higher
                      conversion ratios, a novel route towards DCI was established
                      by utilizing the promiscuous activity of two plant-derived
                      enzymes, the NAD+-dependent d-ononitol dehydrogenase MtOEPa
                      and the NADPH-dependent d-pinitol dehydrogenase MtOEPb from
                      Medicago truncatula (barrelclover). Heterologous production
                      of these enzymes in the chassis strain led to the production
                      of 1.6 g/L DCI from 10 g/L MI. For replacing the substrate
                      MI by glucose, the two plant genes were co-expressed with
                      the endogenous myo-inositol-1-phosphate synthase gene ino1
                      either as a synthetic operon or using a novel, bicistronic
                      T7-based expression vector. With the single operon
                      construct, 0.75 g/L DCI was formed from 20 g/L glucose,
                      whereas with the bicistronic construct 1.2 g/L DCI was
                      obtained, disclosing C. glutamicum as an attractive host for
                      of d-chiro-inositol production.},
      cin          = {IBG-1},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2171 - Biological and environmental resources for
                      sustainable use (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2171},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {37146873},
      UT           = {WOS:001005297800001},
      doi          = {10.1016/j.ymben.2023.04.013},
      url          = {https://juser.fz-juelich.de/record/1007355},
}