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@PHDTHESIS{Wachtmeister:573792,
author = {Wachtmeister, Jochen},
othercontributors = {Rother, Dörte and Blank, Lars M.},
title = {{M}odularization and optimization of enzymatic reactions
applying whole cell biocatalysis in micro-aqueous solvent
systems},
school = {RWTH Aachen},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2016-03741},
pages = {1 Online-Ressolurce (XI, 155 Seiten) : Illustrationen,
Diagramme},
year = {2016},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University; Dissertation, RWTH Aachen, 2016},
abstract = {Growing understanding of enzymatic reactions and their
utilization for synthetic purposes has led to a rising
interest in development of artificial, biocatalytic
multi-step reactions. These synthetic enzyme cascades
selectively convert inexpensive substrates into valuable
compounds of varying applications. Despite their many
advantages, the productivity of biocatalytic cascade
reactions is oftentimes considered unsatisfactory for
implementation into industrial scale processes. To overcome
this limitation and facilitate investigation, application,
optimization, and scale-up of biocatalytic cascade reactions
was the objective of this thesis. Representing a valuable
chiral building block for pharmaceutical synthesis,
1-phenylpropane-1,2-diol was chosen as a model product,
accessed by subsequent carboligation and oxidoreduction.In
order to increase the economic and ecologic relevance of the
model process and of synthetic enzyme cascades in general,
lyophilized whole cell catalyst was used in a micro-aqueous
solvent system. In doing so, a cheap and stable catalyst
formulation was employed, independent of costly external
cofactor addition. The cofactor, supplied by the whole cell
catalyst itself, was recycled by substrate-coupled
regeneration. Furthermore, the reaction in organic solvent
enabled outstandingly high substrate and product titers
together with facilitated downstream processing by
straightforward solvent evaporation.To enable an easy
cascade investigation and setup, the compartmentalized
entrapment or encapsulation of whole cell catalyst was
envisaged, allowing to serve as a catalytic module.
Therefore, whole cell catalyst was retained in a polymeric
membrane, resulting in a catalytic teabag. The catalytic
teabag was proven a useful modularization tool, enabling (i)
simplified and flexible handling and combination of
biocatalysts, (ii) straightforward catalyst recovery and
recycling, (iii) facilitated cascade optimization and
set-up, as well as (iv) small scale preparative production
of chiral compounds. In a second project part, the teabag
approach was demonstrated scalable up to 150 mL,
facilitating the gram-scale manufacturing of
(1R,2R)-1-phenylpropane-1,2-diol in a 1-pot 2-step cascade.
As suitable reaction vessel, not only novel reactor concepts
such as the SpinChem reactor (Nordic Chemquest AB) were
proven useful, but also ubiquitously available lab
equipment. In a third project part, the investigated
concepts were demonstrated transferable to two more
catalysts, now granting stereoselective access to all four
diastereoisomers of 1-phenylpropane-1,2-diol at industrially
relevant product concentrations. To achieve this goal, a
combination of reaction engineering and solvent engineering
was applied. By the implementation of “smart” diol
co-substrates up to 90 $mol\%$ of co-substrate could be
saved during oxidoreduction in two of the final cascades. At
the same time, product yield and space-time-yields obtained
met industrial benchmarks while outstandingly small amounts
of waste were generated.In summary, the investigation of
synthetic enzyme cascades was strongly facilitated by the
teabag approach. The developed module is quickly
manufactured and easily manageable, also by users
unexperienced in handling of biological systems and can even
be used for the preparative production of chiral compounds.
The combination of solvent and reaction engineering allowed
exceeding industrial threshold and thus illustrated the
potential of synthetic enzyme cascades even beyond the
investigatory scale.},
cin = {163930 / 160000 / 161700},
ddc = {570},
cid = {$I:(DE-82)163930_20160511$ / $I:(DE-82)160000_20140620$ /
$I:(DE-82)161700_20140620$},
pnm = {GRK 1166 - GRK 1166: Biokatalyse in unkonventionellen
Medien - Ionische Flüssigkeiten, organische Lösungsmittel,
überkritische Fluide und Gase als Reaktionsphasen für
biokatalysierte Synthesen (811503)},
pid = {G:(GEPRIS)811503},
typ = {PUB:(DE-HGF)11},
urn = {urn:nbn:de:hbz:82-rwth-2016-037410},
url = {https://publications.rwth-aachen.de/record/573792},
}
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