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@ARTICLE{Jayaraman:909762,
      author       = {Jayaraman, Kumaresan and Trachtmann, Natalia and Sprenger,
                      Georg A. and Gohlke, Holger},
      title        = {{P}rotein engineering for feedback resistance in
                      3-deoxy-{D}-arabino-heptulosonate 7-phosphate synthase},
      journal      = {Applied microbiology and biotechnology},
      volume       = {106},
      issn         = {0171-1741},
      address      = {New York},
      publisher    = {Springer},
      reportid     = {FZJ-2022-03392},
      pages        = {6505–6517},
      year         = {2022},
      abstract     = {The shikimate pathway delivers aromatic amino acids (AAAs)
                      in prokaryotes, fungi, and plants and is highly utilized in
                      the industrial synthesis of bioactive compounds. Carbon flow
                      into this pathway is controlled by the initial enzyme
                      3-deoxy-D-arabino-heptulosonate 7-phosphate synthase
                      (DAHPS). AAAs produced further downstream, phenylalanine
                      (Phe), tyrosine (Tyr), and tryptophan (Trp), regulate DAHPS
                      by feedback inhibition. Corynebacterium glutamicum, the
                      industrial workhorse for amino acid production, has two
                      isoenzymes of DAHPS, AroF (Tyr sensitive) and AroG (Phe and
                      Tyr sensitive). Here, we introduce feedback resistance
                      against Tyr in the class I DAHPS AroF (AroFcg). We pursued a
                      consensus approach by drawing on structural modeling,
                      sequence and structural comparisons, knowledge of
                      feedback-resistant variants in E. coli homologs, and
                      computed folding free energy changes. Two types of variants
                      were predicted: Those where substitutions putatively either
                      destabilize the inhibitor binding site or directly interfere
                      with inhibitor binding. The recombinant variants were
                      purified and assessed in enzyme activity assays in the
                      presence or absence of Tyr. Of eight AroFcg variants, two
                      $yielded > 80\%$ (E154N) $and > 50\%$ (P155L)
                      residual activity at 5 mM Tyr and $showed > 50\%$
                      specific activity of the wt AroFcg in the absence of Tyr.
                      Evaluation of two and four further variants at positions 154
                      and 155 yielded E154S, completely resistant to 5 mM Tyr, and
                      P155I, which behaves similarly to P155L. Hence,
                      feedback-resistant variants were found that are unlikely to
                      evolve by point mutations from the parental gene and, thus,
                      would be missed by classical strain engineering.},
      cin          = {IBG-4 / IBI-7 / JSC / NIC},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-4-20200403 / I:(DE-Juel1)IBI-7-20200312 /
                      I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406},
      pnm          = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
                      (SDLs) and Research Groups (POF4-511) / 2171 - Biological
                      and environmental resources for sustainable use (POF4-217) /
                      2172 - Utilization of renewable carbon and energy sources
                      and engineering of ecosystem functions (POF4-217) /
                      Forschergruppe Gohlke $(hkf7_20200501)$ / 5241 - Molecular
                      Information Processing in Cellular Systems (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-2171 /
                      G:(DE-HGF)POF4-2172 / $G:(DE-Juel1)hkf7_20200501$ /
                      G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {36109385},
      UT           = {WOS:000854705600002},
      doi          = {10.1007/s00253-022-12166-9},
      url          = {https://juser.fz-juelich.de/record/909762},
}