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@ARTICLE{Gerlach:906758,
author = {Gerlach, Tim and Schain, Jendrik and Söltl, Simone and van
Schie, Morten M. C. H. and Hilgers, Fabienne and
Bitzenhofer, Nora L. and Drepper, Thomas and Rother, Dörte},
title = {{P}hoto-{R}egulation of {E}nzyme {A}ctivity: {T}he
{I}nactivation of a {C}arboligase with {G}enetically
{E}ncoded {P}hotosensitizer {F}usion {T}ags},
journal = {Frontiers in catalysis},
volume = {2},
issn = {2673-7841},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {FZJ-2022-01673},
pages = {835919},
year = {2022},
abstract = {Genetically encoded photosensitizers are able to produce
reactive oxygen species upon illumination and are exploited
in a wide range of applications, especially in the medical
field. In this work, we envisioned to further apply these
genetically encoded photosensitizers for the light-dependent
control of single enzymes in multi-step biocatalysis. One of
the challenges in the application of several enzymes in a
cascade is the unwanted cross-reactivity of these
biocatalysts on reaction intermediates when all enzymes are
simultaneously present in the reaction. As one strategy to
address this issue, we investigated whether the introduction
of genetically encoded photosensitizers as fusion tags would
allow the selective inactivation of enzymes after successful
transformation by simply turning on light. We tested five
different photosensitizers as molecular biological fusion
tags to inactivate the pyruvate decarboxylase variant
E469G/W543H from Acetobacter pasteurianus. Dimeric
photosensitizer tags, like the flavin-binding fluorescent
proteins from Bacillus subtilis and Pseudomonas putida
showed the tendency to form insoluble protein aggregates in
combination with the tetrameric carboligase. Enzyme activity
was, to some extent, retained in these aggregates, but the
handling of the insoluble aggregates proved to be
unfeasible. Monomeric photosensitizer tags appeared to be
much more suitable when fused to the tetrameric enzyme. In
the dark, the singlet oxygen photosensitizing protein
(SOPP3)-tagged carboligase retained $79\%$ of its activity
as compared to the unfused enzyme. Upon blue light exposure,
the SOPP3 tag showed the best specific inactivation and
enabled complete inactivation of the carboligase within 30
min. SOPP3 is thus seen as a promising photosensitizer tag
to be applied in future multi-step enzyme cascades to
overcome the challenge of cross-reactivity.},
cin = {IBG-1 / IMET},
ddc = {540},
cid = {I:(DE-Juel1)IBG-1-20101118 / I:(DE-Juel1)IMET-20090612},
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},
doi = {10.3389/fctls.2022.835919},
url = {https://juser.fz-juelich.de/record/906758},
}