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@ARTICLE{Ramp:909763,
      author       = {Ramp, Paul and Pfleger, Christopher and Dittrich, Jonas and
                      Mack, Christina and Gohlke, Holger and Bott, Michael},
      title        = {{P}hysiological, {B}iochemical, and {S}tructural
                      {B}ioinformatic {A}nalysis of the {M}ultiple {I}nositol
                      {D}ehydrogenases from {C}orynebacterium glutamicum},
      journal      = {Microbiology spectrum},
      volume       = {10},
      number       = {5},
      issn         = {2165-0497},
      address      = {Birmingham, Ala.},
      publisher    = {ASM},
      reportid     = {FZJ-2022-03393},
      pages        = {e01950-22},
      year         = {2022},
      abstract     = {Inositols (cyclohexanehexols) comprise nine isomeric cyclic
                      sugar alcohols, several of which occur in all domains of
                      life with various functions. Many bacteria can utilize
                      inositols as carbon and energy sources via a specific
                      pathway involving inositol dehydrogenases (IDHs) as the
                      first step of catabolism. The microbial cell factory
                      Corynebacterium glutamicum can grow with myo-inositol as a
                      sole carbon source. Interestingly, this species encodes
                      seven potential IDHs, raising the question of the reason for
                      this multiplicity. We therefore investigated the seven IDHs
                      to determine their function, activity, and selectivity
                      toward the biologically most important isomers myo-,
                      scyllo-, and d-chiro-inositol. We created an ΔIDH strain
                      lacking all seven IDH genes, which could not grow on the
                      three inositols. scyllo- and d-chiro-inositol were
                      identified as novel growth substrates of C. glutamicum.
                      Complementation experiments showed that only four of the
                      seven IDHs (IolG, OxiB, OxiD, and OxiE) enabled growth of
                      the ΔIDH strain on two of the three inositols. The kinetics
                      of the four purified enzymes agreed with the complementation
                      results. IolG and OxiD are NAD+-dependent IDHs accepting
                      myo- and d-chiro-inositol but not scyllo-inositol. OxiB is
                      an NAD+-dependent myo-IDH with a weak activity also for
                      scyllo-inositol but not for d-chiro-inositol. OxiE on the
                      other hand is an NAD+-dependent scyllo-IDH showing also good
                      activity for myo-inositol and a very weak activity for
                      d-chiro-inositol. Structural models, molecular docking
                      experiments, and sequence alignments enabled the
                      identification of the substrate binding sites of the active
                      IDHs and of residues allowing predictions on the substrate
                      specificity. IMPORTANCE myo-, scyllo-, and d-chiro-inositol
                      are C6 cyclic sugar alcohols with various biological
                      functions, which also serve as carbon sources for microbes.
                      Inositol catabolism starts with an oxidation to
                      keto-inositols catalyzed by inositol dehydrogenases (IDHs).
                      The soil bacterium C. glutamicum encodes seven potential
                      IDHs. Using a combination of microbiological, biochemical,
                      and modeling approaches, we analyzed the function of these
                      enzymes and identified four IDHs involved in the catabolism
                      of inositols. They possess distinct substrate preferences
                      for the three isomers, and modeling and sequence alignments
                      allowed the identification of residues important for
                      substrate specificity. Our results expand the knowledge of
                      bacterial inositol metabolism and provide an important basis
                      for the rational development of producer strains for these
                      valuable inositols, which show pharmacological activities
                      against, e.g., Alzheimer's disease, polycystic ovarian
                      syndrome, or type II diabetes. Keywords: Corynebacterium
                      glutamicum; d-chiro-inositol; enzyme kinetics; inositol
                      dehydrogenase; inositol metabolism; inositols; molecular
                      docking; myo-inositol; scyllo-inositol; structural models.},
      cin          = {IBG-4 / JSC / NIC / IBI-7 / IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-4-20200403 / I:(DE-Juel1)JSC-20090406 /
                      I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)IBI-7-20200312 /
                      I:(DE-Juel1)IBG-1-20101118},
      pnm          = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
                      (SDLs) and Research Groups (POF4-511) / 5241 - Molecular
                      Information Processing in Cellular Systems (POF4-524) / 2171
                      - Biological and environmental resources for sustainable use
                      (POF4-217) / Forschergruppe Gohlke $(hkf7_20200501)$ / BioSC
                      - Bioeconomy Science Center (BioSC) /
                      $BioökonomieREVIER_INNO:$ Entwicklung der Modellregion
                      BioökonomieREVIER Rheinland, TP A (031B0918A)},
      pid          = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-5241 /
                      G:(DE-HGF)POF4-2171 / $G:(DE-Juel1)hkf7_20200501$ /
                      G:(DE-Juel1)BioSC / G:(BMBF)031B0918A},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {36094194},
      UT           = {WOS:000854191500002},
      doi          = {10.1128/spectrum.01950-22},
      url          = {https://juser.fz-juelich.de/record/909763},
}