% 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{Weber:1006586,
      author       = {Weber, Douglas and de Souza Bastos, Lucas and Winkler,
                      Margit and Ni, Yeke and Aliev, Abil E. and Hailes, Helen C.
                      and Rother, Doerte},
      title        = {{M}ulti-enzyme catalysed processes using purified and
                      whole-cell biocatalysts towards a 1,3,4-substituted
                      tetrahydroisoquinoline},
      journal      = {RSC Advances},
      volume       = {13},
      number       = {15},
      issn         = {2046-2069},
      address      = {London},
      publisher    = {RSC Publishing},
      reportid     = {FZJ-2023-01727},
      pages        = {10097 - 10109},
      year         = {2023},
      abstract     = {In this work, two multi-enzyme catalysed processes to
                      access a 1,3,4-substituted tetrahydroisoquinoline (THIQ),
                      using either purified enzymes or lyophilised whole-cell
                      catalysts, are presented. A key focus was the first step in
                      which the reduction of 3-hydroxybenzoic acid (3-OH-BZ) into
                      3-hydroxybenzaldehyde (3-OH-BA) was catalysed by a
                      carboxylate reductase (CAR) enzyme. Incorporation of the
                      CAR-catalysed step enables substituted benzoic acids as the
                      aromatic components, which can potentially be obtained from
                      renewable resources by microbial cell factories. In this
                      reduction, the implementation of an efficient cofactor
                      regeneration system of both ATP and NADPH was crucial. Two
                      different recycling approaches, either using purified
                      enzymes or lyophilised whole-cells, were established and
                      compared. Both of them showed high conversions of the acid
                      into 3-OH-BA $(>80\%).$ However, the whole-cell system
                      showed superior performance because it allowed the
                      combination of the first and second steps into a one-pot
                      cascade with excellent HPLC yields $(>99\%,$ enantiomeric
                      excess (ee) ≥ $95\%)$ producing the intermediate
                      3-hydroxyphenylacetylcarbinol. Moreover, enhanced substrate
                      loads could be achieved compared to the system employing
                      only purified enzymes. The third and fourth steps were
                      performed in a sequential mode to avoid cross-reactivities
                      and the formation of several side products. Thus,
                      (1R,2S)-metaraminol could be formed with high HPLC yields
                      $(>90\%,$ isomeric content (ic) ≥ $95\%)$ applying either
                      purified or whole-cell transaminases from Bacillus
                      megaterium (BmTA) or Chromobacterium violaceum (Cv2025).
                      Finally, the cyclisation step was performed using either a
                      purified or lyophilised whole-cell norcoclaurine synthase
                      variant from Thalictrum flavum (ΔTfNCS-A79I), leading to
                      the formation of the target THIQ product with high HPLC
                      yields $(>90\%,$ ic > $90\%).$ As many of the educts applied
                      are from renewable resources and a complex product with
                      three chiral centers can be gained by only four highly
                      selective steps, a very step- and atom efficient approach to
                      stereoisomerically pure THIQ is shown.},
      cin          = {IBG-1},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2172 - Utilization of renewable carbon and energy sources
                      and engineering of ecosystem functions (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2172},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {37006360},
      UT           = {WOS:000962147800001},
      doi          = {10.1039/D3RA01210G},
      url          = {https://juser.fz-juelich.de/record/1006586},
}