MPI Colloquia Series: Dr. Dörte Rother,Synthetic enzyme cascades – from set-up to economic and ecologic efficiency studies
MPI Colloquia Series: Dr. Dörte Rother
- Date: Jan 24, 2019
- Time: 04:00 PM - 05:00 PM (Local Time Germany)
- Speaker: Dr. Dörte Rother
- Institute of Bio- and Geosciences, Forschungszentrum Jülich
- Location: Max Planck Institute Magdeburg
- Room: Big Seminar Room "Prigogine"
- Contact: sek-bpe@mpi-magdeburg.mpg.de
The Max Planck Institute Magdeburg invites you to its series of colloquia.
Top-class scientists, from notable German and worldwide research
institutions, give a survey of their research work. Everybody who is
interested, is invited to attend.
Abstract
Enzymatic multi-step reactions offer significant potential to yield
industrially relevant chiral intermediates and building blocks with
excellent stereoselectivities. Still, the access to economically
feasible product concentrations can be a challenge. By using an
integrated engineering approach, encompassing enzyme engineering,
reaction optimisation and optimal process design, this challenge can be
adressed. This presentation focuses on the development of synthetic
enzyme cascades for the production of pharmaceutically active
ingredients meeting not only requirements on high selectivities (>98
%) therewith reducing waste, but also reaching product concentrations
>50 g/l.
By the flexible combination of enzymes with varying
substrate preferences or stereoselectivities, the access to product
platforms is possible. E.g. starting from easily available aldehydes or
keto acids, chiral amino alcohols can be synthesised by a combination of
an enzymatically catalysed carboligation and a transamination step.
Depending on the substitution pattern of the starting material, products
like nor(pseudo)ephedrine[1], methoxamine or metaraminol[2] are
accessible. By the combination of (R)- and (S)-selective catalysts in a
modular way, in most cases all four stereoisomers of the respective
amino alcohol can be gained. Recently, 1-amino-1-phenylpropan-2-ol
wascatalysed in a repetitive batch mode using immobilised catalysts to
enhanced specific space-time-yields while cutting on catalyst costs.
On top, tetrahydroisoquinolines (THIQ) containing three chiral centres can be synthesised by
the addition of a cyclisation step. This step can be either catalysed by a norcoclaurine
synthase or by phosphate giving stereocomplementary products.[2]
To
further increase ecologic and economic efficiency, we investigate the
potential in running multi-step biocatalysis in (environmentally benign)
organic solvents or neat substrate systems. Whole cell
biotransformations in micro-aqueous reaction systems do not only allow
addition of poorly water-soluble substrates in high concentrations, but
also facilitate
downstream processing. As an example, the production
of several vicinal diols was possible in a 2-step 1-pot cascade in
micro-aqueous organic solvents with product concentration up to 440 mM
and space-time-yields up to 330 g L-1 d-1 (ee/de >99 %).[3] Novel
set-ups of this system include coproduct recycling as well as in situ
product removal.[4]
[1] T. Sehl, H. C. Hailes, J. M. Ward, U. Menyes, M. Pohl, D. Rother, Green Chem. 2014,
16, 3341-48; T. Sehl, H. C. Hailes, J. M. Ward, R. Wardenga, E. von Lieres, H.
Offermann, R. Westphal, M. Pohl, D. Rother, Angew. Chem. Int. Ed. 2013, 52, 6772-75.
[2] V. Erdmann, B. R. Lichman, J. Zhao, R. C. Simon, W. Kroutil, J. M. Ward, H. C. Hailes,
D. Rother, Angew. Chem. Int. Ed. 2017, 56, 12503-07.
[3] A. Jakoblinnert, D. Rother. Green Chem. 2014, 16, 3472-82; J. Wachtmeister, A.
Jakoblinnert, D.Rother, Org. Process Res. Dev. 2014, 20 (10), 1744–53.
[4] R. Oeggl, T. Maßmann, A. Jupke, D. Rother. ACS Sustainable Chem. Eng. 2018, 6 (9),
11819–26.