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@ARTICLE{Ksters:890631,
author = {Küsters, Kira and Pohl, Martina and Krauss, Ulrich and
Ölçücü, Gizem and Albert, Sandor and Jaeger, Karl-Erich
and Wiechert, Wolfgang and Oldiges, Marco},
title = {{C}onstruction and comprehensive characterization of an
{E}c{LDC}c-{C}at{IB} set - varying linkers and aggregation
inducing tags},
journal = {Microbial cell factories},
volume = {20},
number = {1},
issn = {1475-2859},
address = {London},
publisher = {Biomed Central},
reportid = {FZJ-2021-01086},
pages = {49},
year = {2021},
abstract = {BackgroundIn recent years, the production of inclusion
bodies that retained substantial catalytic activity was
demonstrated. These catalytically active inclusion bodies
(CatIBs) were formed by genetic fusion of an aggregation
inducing tag to a gene of interest via short linker
polypeptides and overproduction of the resulting gene fusion
in Escherichia coli. The resulting CatIBs are known for
their high stability, easy and cost efficient production,
and recyclability and thus provide an interesting
alternative to conventionally immobilized
enzymes.ResultsHere, we present the construction and
characterization of a CatIB set of the lysine decarboxylase
from Escherichia coli (EcLDCc), constructed via Golden Gate
Assembly. A total of ten EcLDCc variants consisting of
combinations of two linker and five aggregation inducing tag
sequences were generated. A flexible Serine/Glycine (SG)- as
well as a rigid Proline/Threonine (PT)-Linker were tested in
combination with the artificial peptides (18AWT, L6KD and
GFIL8) or the coiled-coil domains (TDoT and 3HAMP) as
aggregation inducing tags. The linkers were fused to the
C-terminus of the EcLDCc to form a linkage between the
enzyme and the aggregation inducing tags. Comprehensive
morphology and enzymatic activity analyses were performed
for the ten EcLDCc-CatIB variants and a wild type EcLDCc
control to identify the CatIB variant with the highest
activity for the decarboxylation of l-lysine to
1,5-diaminopentane. Interestingly, all of the CatIB variants
possessed at least some activity, whilst most of the
combinations with the rigid PT-Linker showed the highest
conversion rates. EcLDCc-PT-L6KD was identified as the best
of all variants allowing a volumetric productivity of
457 g L− 1 d− 1 and a specific volumetric
productivity of 256 g L− 1 d− 1 gCatIB−1.
Noteworthy, wild type EcLDCc, without specific aggregation
inducing tags, also partially formed CatIBs, which, however
showed lower activity compared to most of the newly
constructed CatIB variants (volumetric productivity: 219 g
L− 1 d− 1, specific volumetric activity: 106 g
L− 1 d− 1 gCatIB− 1). Furthermore, we demonstrate
that microscopic analysis can serve as a tool to find CatIB
producing strains and thus allow for prescreening at an
early stage to save time and resources.ConclusionsOur
results clearly show that the choice of linker and
aggregation inducing tag has a strong influence on the
morphology and the enzymatic activity of the CatIBs.
Strikingly, the linker had the most pronounced influence on
these characteristics.},
cin = {IBG-1 / IMET},
ddc = {570},
cid = {I:(DE-Juel1)IBG-1-20101118 / I:(DE-Juel1)IMET-20090612},
pnm = {2171 - Biological and environmental resources for
sustainable use (POF4-217)},
pid = {G:(DE-HGF)POF4-2171},
typ = {PUB:(DE-HGF)16},
pubmed = {33596923},
UT = {WOS:000620983800004},
doi = {10.1186/s12934-021-01539-w},
url = {https://juser.fz-juelich.de/record/890631},
}