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@ARTICLE{Ramp:894472,
author = {Ramp, Paul and Lehnert, Alexander and Matamouros, Susana
and Wirtz, Astrid and Baumgart, Meike and Bott, Michael},
title = {{M}etabolic engineering of {C}orynebacterium glutamicum for
production of scyllo-inositol, a drug candidate against
{A}lzheimer's disease},
journal = {Metabolic engineering},
volume = {67},
issn = {1096-7176},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {FZJ-2021-03247},
pages = {173 - 185},
year = {2021},
abstract = {Scyllo-inositol has been identified as a potential drug for
the treatment of Alzheimer's disease. Therefore,
cost-efficient processes for the production of this compound
are desirable. In this study, we analyzed and engineered
Corynebacterium glutamicum with the aim to develop
competitive scyllo-inositol producer strains. Initial
studies revealed that C. glutamicum naturally produces
scyllo-inositol when cultured with myo-inositol as carbon
source. The conversion involves NAD+-dependent oxidation of
myo-inositol to 2-keto-myo-inositol followed by
NADPH-dependent reduction to scyllo-inositol. Use of
myo-inositol for biomass formation was prevented by deletion
of a cluster of 16 genes involved in myo-inositol catabolism
(strain MB001(DE3)Δiol1). Deletion of a second cluster of
four genes (oxiC-cg3390-oxiD-oxiE) related to inositol
metabolism prevented conversion of 2-keto-myo-inositol to
undesired products causing brown coloration (strain
MB001(DE3)Δiol1Δiol2). The two chassis strains were used
for plasmid-based overproduction of myo-inositol
dehydrogenase (IolG) and scyllo-inositol dehydrogenase
(IolW). In BHI medium containing glucose and myo-inositol, a
complete conversion of the consumed myo-inositol into
scyllo-inositol was achieved with the Δiol1Δiol2 strain.
To enable scyllo-inositol production from cheap carbon
sources, myo-inositol 1-phosphate synthase (Ino1) and
myo-inositol 1-phosphatase (ImpA), which convert glucose
6-phosphate into myo-inositol, were overproduced in addition
to IolG and IolW using plasmid pSI. Strain
MB001(DE3)Δiol1Δiol2 (pSI) produced 1.8 g/L
scyllo-inositol from 20 g/L glucose and even 4.4 g/L
scyllo-inositol from 20 g/L sucrose within 72 h. Our results
demonstrate that C. glutamicum is an attractive host for the
biotechnological production of scyllo-inositol and
potentially further myo-inositol-derived products.},
cin = {IBG-1},
ddc = {610},
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 = {pmid:34224896},
UT = {WOS:000697032300008},
doi = {10.1016/j.ymben.2021.06.011},
url = {https://juser.fz-juelich.de/record/894472},
}