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@ARTICLE{Ramp:894472,
      author       = {Ramp, Paul and Lehnert, Alexander and Matamouros, Susana
                      and Wirtz, Astrid and Baumgart, Meike and Bott, Michael},
      title        = {{M}etabolic engineering of {C}orynebacterium glutamicum for
                      production of scyllo-inositol, a drug candidate against
                      {A}lzheimer's disease},
      journal      = {Metabolic engineering},
      volume       = {67},
      issn         = {1096-7176},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2021-03247},
      pages        = {173 - 185},
      year         = {2021},
      abstract     = {Scyllo-inositol has been identified as a potential drug for
                      the treatment of Alzheimer's disease. Therefore,
                      cost-efficient processes for the production of this compound
                      are desirable. In this study, we analyzed and engineered
                      Corynebacterium glutamicum with the aim to develop
                      competitive scyllo-inositol producer strains. Initial
                      studies revealed that C. glutamicum naturally produces
                      scyllo-inositol when cultured with myo-inositol as carbon
                      source. The conversion involves NAD+-dependent oxidation of
                      myo-inositol to 2-keto-myo-inositol followed by
                      NADPH-dependent reduction to scyllo-inositol. Use of
                      myo-inositol for biomass formation was prevented by deletion
                      of a cluster of 16 genes involved in myo-inositol catabolism
                      (strain MB001(DE3)Δiol1). Deletion of a second cluster of
                      four genes (oxiC-cg3390-oxiD-oxiE) related to inositol
                      metabolism prevented conversion of 2-keto-myo-inositol to
                      undesired products causing brown coloration (strain
                      MB001(DE3)Δiol1Δiol2). The two chassis strains were used
                      for plasmid-based overproduction of myo-inositol
                      dehydrogenase (IolG) and scyllo-inositol dehydrogenase
                      (IolW). In BHI medium containing glucose and myo-inositol, a
                      complete conversion of the consumed myo-inositol into
                      scyllo-inositol was achieved with the Δiol1Δiol2 strain.
                      To enable scyllo-inositol production from cheap carbon
                      sources, myo-inositol 1-phosphate synthase (Ino1) and
                      myo-inositol 1-phosphatase (ImpA), which convert glucose
                      6-phosphate into myo-inositol, were overproduced in addition
                      to IolG and IolW using plasmid pSI. Strain
                      MB001(DE3)Δiol1Δiol2 (pSI) produced 1.8 g/L
                      scyllo-inositol from 20 g/L glucose and even 4.4 g/L
                      scyllo-inositol from 20 g/L sucrose within 72 h. Our results
                      demonstrate that C. glutamicum is an attractive host for the
                      biotechnological production of scyllo-inositol and
                      potentially further myo-inositol-derived products.},
      cin          = {IBG-1},
      ddc          = {610},
      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:34224896},
      UT           = {WOS:000697032300008},
      doi          = {10.1016/j.ymben.2021.06.011},
      url          = {https://juser.fz-juelich.de/record/894472},
}