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@ARTICLE{Beer:119632,
      author       = {R. Beer and K. Herbst and N. Ignatiadis and I. Kats and L.
                      Adlung$^*$ and H. Meyer and D. Niopek$^*$ and T.
                      Christiansen and F. Georgi and N. Kurzawa and J. Meichsner
                      and S. Rabe and A. Riedel and J. Sachs and J. Schessner and
                      F. Schmidt and P. Walch and K. Niopek$^*$ and T.
                      Heinemann$^*$ and R. Eils$^*$ and B. Di Ventura$^*$},
      title        = {{C}reating functional engineered variants of the
                      single-module non-ribosomal peptide synthetase {I}nd{C} by
                      {T} domain exchange.},
      journal      = {Molecular BioSystems},
      volume       = {10},
      number       = {7},
      issn         = {1742-2051},
      address      = {Cambridge},
      publisher    = {Royal Society of Chemistry},
      reportid     = {DKFZ-2017-00263},
      pages        = {1709 -},
      year         = {2014},
      abstract     = {Non-ribosomal peptide synthetases (NRPSs) are enzymes that
                      catalyze ribosome-independent production of small peptides,
                      most of which are bioactive. NRPSs act as peptide assembly
                      lines where individual, often interconnected modules each
                      incorporate a specific amino acid into the nascent chain.
                      The modules themselves consist of several domains that
                      function in the activation, modification and condensation of
                      the substrate. NRPSs are evidently modular, yet experimental
                      proof of the ability to engineer desired permutations of
                      domains and modules is still sought. Here, we use a
                      synthetic-biology approach to create a small library of
                      engineered NRPSs, in which the domain responsible for
                      carrying the activated amino acid (T domain) is exchanged
                      with natural or synthetic T domains. As a model system, we
                      employ the single-module NRPS IndC from Photorhabdus
                      luminescens that produces the blue pigment indigoidine. As
                      chassis we use Escherichia coli. We demonstrate that
                      heterologous T domain exchange is possible, even for T
                      domains derived from different organisms. Interestingly,
                      substitution of the native T domain with a synthetic one
                      enhanced indigoidine production. Moreover, we show that
                      selection of appropriate inter-domain linker regions is
                      critical for functionality. Taken together, our results
                      extend the engineering avenues for NRPSs, as they point out
                      the possibility of combining domain sequences coming from
                      different pathways, organisms or from conservation criteria.
                      Moreover, our data suggest that NRPSs can be rationally
                      engineered to control the level of production of the
                      corresponding peptides. This could have important
                      implications for industrial and medical applications.},
      keywords     = {Bacterial Proteins (NLM Chemicals) / Peptides (NLM
                      Chemicals) / Piperidones (NLM Chemicals) / indigoidine (NLM
                      Chemicals) / Peptide Synthases (NLM Chemicals) /
                      non-ribosomal peptide synthase (NLM Chemicals)},
      cin          = {A150 / B080 / A170},
      ddc          = {540},
      cid          = {I:(DE-He78)A150-20160331 / I:(DE-He78)B080-20160331 /
                      I:(DE-He78)A170-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24457530},
      doi          = {10.1039/c3mb70594c},
      url          = {https://inrepo02.dkfz.de/record/119632},
}