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@ARTICLE{Schwanemann:1006798,
author = {Schwanemann, Tobias and Otto, Maike and Wynands, Benedikt
and Marienhagen, Jan and Wierckx, Nick},
title = {{A} {P}seudomonas taiwanensis {M}alonyl-{C}o{A} platform
strain for polyketide synthesis},
journal = {Metabolic engineering},
volume = {77},
issn = {1096-7176},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {FZJ-2023-01851},
pages = {219-230},
year = {2023},
note = {Biotechnologie 1},
abstract = {Malonyl-CoA is a central precursor for biosynthesis of a
wide range of complex secondary metabolites. The development
of platform strains with increased malonyl-CoA supply can
contribute to the efficient production of secondary
metabolites, especially if such strains exhibit high
tolerance towards these chemicals. In this study,
Pseudomonas taiwanensis VLB120 was engineered for increased
malonyl-CoA availability to produce bacterial and
plant-derived polyketides. A multi-target metabolic
engineering strategy focusing on decreasing the malonyl-CoA
drain and increasing malonyl-CoA precursor availability, led
to an increased production of various malonyl-CoA-derived
products, including pinosylvin, resveratrol and flaviolin.
The production of flaviolin, a molecule deriving from five
malonyl-CoA molecules, was doubled compared to the parental
strain by this malonyl-CoA increasing strategy.
Additionally, the engineered platform strain enabled
production of up to 84 mg L−1 resveratrol from
supplemented p-coumarate. One key finding of this study was
that acetyl-CoA carboxylase overexpression majorly
contributed to an increased malonyl-CoA availability for
polyketide production in dependence on the used
strain-background and whether downstream fatty acid
synthesis was impaired, reflecting its complexity in
metabolism. Hence, malonyl-CoA availability is primarily
determined by competition of the production pathway with
downstream fatty acid synthesis, while supply reactions are
of secondary importance for compounds that derive directly
from malonyl-CoA in Pseudomonas.},
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 = {37031949},
UT = {WOS:001027176900001},
doi = {10.1016/j.ymben.2023.04.001},
url = {https://juser.fz-juelich.de/record/1006798},
}