% 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{Brands:896715,
      author       = {Brands, Stefanie and Brass, Hannah and Klein, Andreas and
                      Sikkens, Jarno G. and Davari, Mehdi D. and Pietruszka, Jörg
                      and Ruff, Anna Joëlle and Schwaneberg, Ulrich},
      title        = {{K}now{V}olution of prodigiosin ligase {P}ig{C} towards
                      condensation of short-chain prodiginines},
      journal      = {Catalysis science $\&$ technology},
      volume       = {11},
      number       = {8},
      issn         = {2044-4761},
      address      = {London},
      publisher    = {RSC Publ.},
      reportid     = {FZJ-2021-03548},
      pages        = {2805 - 2815},
      year         = {2021},
      abstract     = {Prodigiosin ligase PigC catalyses the final condensation
                      step in the prodigiosin biosynthesis of Serratia marcescens,
                      in which two pyrrolic precursor molecules are fused linearly
                      to form tripyrrolic red prodiginines. Prodiginine compounds
                      attracted interest as pharmaceutical agents lately since
                      their structural elucidation in the 1960s due to their
                      multiple bioactivities (e.g., antibiotic, nematicidal or
                      anticancer effects). As a key enzyme in the prodigiosin
                      biosynthesis pathway, PigC presents a bottleneck for
                      efficient broad-range prodiginine production because of its
                      limited substrate acceptance. In particular, biosynthesis of
                      short-chain prodiginines is of high synthetic interest due
                      to their effective anticancer properties. In this study,
                      PigC was successfully engineered to efficiently accept
                      short-chain pyrroles following the KnowVolution strategy,
                      which provided variants with up to 10.7-fold increased kcat
                      (7.5 ± 0.4 min−1 compared to 0.7 ± 0.1 min−1 for the
                      PigC wild type), and a nearly 40-fold enhanced catalytic
                      efficiency (kcat/KM = 23.9 ± 3.6 mM−1 s−1 compared to
                      0.6 ± 0.1 mM−1 s−1 for the PigC wild type) towards
                      short-chain pyrroles. The final and most active PigC variant
                      S1 carried two amino acid substitutions (I365G/M671V) in the
                      substrate-binding domain close to a substrate tunnel, and
                      showed a pronounced preference for small pyrroles. In
                      summary, the directed evolution campaign on PigC provided
                      engineered variants to open a biosynthetic route for
                      short-chain prodiginines.},
      cin          = {IBOC / IBG-1},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBOC-20090406 / 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},
      UT           = {WOS:000644065100011},
      doi          = {10.1039/D0CY02297G},
      url          = {https://juser.fz-juelich.de/record/896715},
}