% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Krger:917136,
      author       = {Krüger, Aileen and Frunzke, Julia},
      title        = {{A} pseudokinase version of the histidine kinase {C}hr{S}
                      promotes high heme tolerance of {C}orynebacterium
                      glutamicum},
      journal      = {Frontiers in microbiology},
      volume       = {13},
      issn         = {1664-302X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {FZJ-2023-00368},
      pages        = {997448},
      year         = {2022},
      note         = {Biotechnologie 1},
      abstract     = {Heme is an essential cofactor for almost all living cells
                      by acting as prosthetic group for various proteins or
                      serving as alternative iron source. However, elevated levels
                      are highly toxic for cells. Several corynebacterial species
                      employ two paralogous, heme-responsive two-component systems
                      (TCS), ChrSA and HrrSA, to cope with heme stress and to
                      maintain intracellular heme homeostasis. Significant
                      cross-talk at the level of phosphorylation between these
                      systems was previously demonstrated. In this study, we have
                      performed a laboratory evolution experiment to adapt
                      Corynebacterium glutamicum to increasing heme levels.
                      Isolated strains showed a highly increased tolerance to heme
                      growing at concentrations of up to 100 μM. The strain
                      featuring the highest heme tolerance harbored a frameshift
                      mutation in the catalytical and ATPase-domain (CA-domain) of
                      the chrS gene, converting it into a catalytically-inactive
                      pseudokinase $(ChrS_CA-fs).$ Reintroduction of the
                      respective mutation in the parental C. glutamicum strain
                      confirmed high heme tolerance and showed a drastic
                      upregulation of hrtBA encoding a heme export system,
                      conserved in Firmicutes and Actinobacteria. The strain
                      encoding the ChrS pseudokinase variant showed significantly
                      higher heme tolerance than a strain lacking chrS. Mutational
                      analysis revealed that induction of hrtBA in the evolved
                      strain is solely mediated via the cross-phosphorylation of
                      the response regulator (RR) ChrA by the kinase HrrS and
                      BACTH assays revealed the formation of heterodimers between
                      HrrS and ChrS. Overall, our results emphasize an important
                      role of the ChrS pseudokinase in high heme tolerance of the
                      evolved C. glutamicum and demonstrate the promiscuity in
                      heme-dependent signaling of the paralogous two-component
                      systems facilitating fast adaptation to changing
                      environmental conditions.},
      cin          = {IBG-1},
      ddc          = {570},
      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       = {36160252},
      UT           = {WOS:000859687500001},
      doi          = {10.3389/fmicb.2022.997448},
      url          = {https://juser.fz-juelich.de/record/917136},
}