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@ARTICLE{Mller:897399,
author = {Müller, Carolin and Igwe, Chika L. and Wiechert, Wolfgang
and Oldiges, Marco},
title = {{S}caling production of {GFP}1-10 detector protein in
{E}. coli for secretion screening by split {GFP} assay},
journal = {Microbial cell factories},
volume = {20},
number = {1},
issn = {1475-2859},
address = {London},
publisher = {Biomed Central},
reportid = {FZJ-2021-03765},
pages = {191},
year = {2021},
abstract = {BackgroundThe split GFP assay is a well-known technology
for activity-independent screening of target proteins. A
superfolder GFP is split into two non-fluorescent parts,
GFP11 which is fused to the target protein and GFP1-10. In
the presence of both, GFP1-10 and the GFP11-tag are
self-assembled and a functional chromophore is formed.
However, it relies on the availability and quality of
GFP1-10 detector protein to develop fluorescence by assembly
with the GFP11-tag connected to the target protein. GFP1-10
detector protein is often produced in small scale shake
flask cultivation and purified from inclusion
bodies.ResultsThe production of GFP1-10 in inclusion bodies
and purification was comprehensively studied based on
Escherichia coli as host. Cultivation in complex and defined
medium as well as different feed strategies were tested in
laboratory-scale bioreactor cultivation and a standardized
process was developed providing high quantity of GFP1-10
detector protein with suitable quality. Split GFP assay was
standardized to obtain robust and reliable assay results
from cutinase secretion strains of Corynebacterium
glutamicum with Bacillus subtilis Sec signal peptides NprE
and Pel. Influencing factors from environmental conditions,
such as pH and temperature were thoroughly
investigated.ConclusionsGFP1-10 detector protein production
could be successfully scaled from shake flask to laboratory
scale bioreactor. A single run yielded sufficient material
for up to 385 96-well plate screening runs. The application
study with cutinase secretory strains showed very high
correlation between measured cutinase activity to split GFP
fluorescence signal proofing applicability for larger
screening studies.},
cin = {IBG-1},
ddc = {570},
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 = {34592997},
UT = {WOS:000702398500001},
doi = {10.1186/s12934-021-01672-6},
url = {https://juser.fz-juelich.de/record/897399},
}