link to homepage

Institute of Bio- and Geosciences

Navigation and service

Projects team 'Synthetic enzyme cascades'

Logo Research Synthetic enzyme cascades

Helmholtz young investigators group `Synthetic enzyme cascades´

Aim of the young investigators group is the development of value generating processes using synthetic enzyme cascades. By the combination of enzyme-, reaction- and process optimisation we combine catalysts which do not occur conjunct in nature. With focus on economic and ecologic efficiency, these enzyme cascades are aimed at providing potent alternatives to classical synthesis strategies. Starting from inexpensive material, highly priced products with applications as building blocks (e.g. for pharmaceuticals) can be gained. In order to access broad platforms of optically active and highly pure products, we built up toolboxes encompassing enzymes with varying substrate preferences and complementary stereo- and regioselectivities. By flexible combinations of these enzymes we are in the position to rapidly act on challenging scientific issues with industrial relevance. An interdisciplinary team of (bio-) chemists, biologists and engineers develops multi-step biotransformations to chiral products with high step- and atom efficient avoiding (toxic) byproducts. Beside multi-step syntheses with purified enzymes and cell extracts in buffered systems, we currently apply and optimise whole cell biotransformations in unconventional media. In focus are micro-aqueous reaction systems or even neat substrate systems. Due to immensely increased substrate concentrations in these non-buffered systems, high product concentrations and space-time-yields can be yielded combined with low production costs. addition, cheap catalyst and cofactor supply and an easy downstream processing renders the application of synthetic enzyme cascades in micro-aqueous reaction systems advantageous.


Projects and Cooperations


Evaluation and optimisation of modular synthetic enzyme cascases by reaction optimisation and solvent engineering

PhD-student: Jochen Wachtmeister

The smart combination of enzymes from different toolboxes will make a broad range of diversely substituted chiral aminoalcohols and diols with high stereoselectivity available. In this project enzymes from different toolboxes will be purified and immobilised and combined to 2-step enzyme cascades in a modular way. Aim of the immobilisation is to remain good enzyme activity after the immobilisation procedure, stably link the enzyme even under activity reducing conditions (e.g. high substrate concentrations or addition of organic solvents) and recycle the catalyst. Those immobilised enzyme modules will than be combined flexibly in order to gain the desired product with destined stereoselectivity. To run the two step synthesis a reactor prototype will be designed.


Cooperation partners: Eric von Lieres (IBG-1, group Modeling & Simulation, D), Marion Ansorge-Schumacher (TU Dresden, D), Antje Spiess (Aachen University, D)

Funded by:

Logo Deutsche Forschungsgemeinschaft

Symbol of Bionoco

in frame of the DFG Research Training Group "Bionoco" GK 11 66 at RWTH Aachen.

Selected publication: Wachtmeister J, Jakoblinnert A, Kulig J, Offermann H, Rother D. 2014. Whole Cell Teabag Catalysis for the Modularisation of Synthetic Enzyme Cascades in Micro-Aqueous Systems. ChemCatChem. 6 (4): 1051-1058.

Two-step cascade reactions for the synthesis of pharmaceutically relevant substituted amino alcohols

PhD-student: Vanessa Erdmann

Chiral vicinal amino alcohols are pharmaceutically active compounds or chemical building blocks with various industrial applications..In previous studies all four stereoisomers of the sympathomimetic amino alcohol nor(pseudo)ephedrine could be achieved in a two-step cascade reaction using ThDP-dependent carboligases and amine transferases with high conversions and selectivities. Now this concept is transferred to substituted amino alcohols. Furthermore, formed amino alcohols are the basis for follow-up syntheses by addition of a third enzymatic step.

cooperation partners: Wolfgang Kroutil (University of Graz, AT), Helen C. Hailes (University College London, UK)

funded by:

Grafic of Helmholtz-Gemeinschaft

Helmholtz Young Investigators Group `Synthetic enzyme cascades´

Catalytic promiscuity of thiamine enzymes – rational combination of structural elements and exploration of the sequence-function space

PhD-student: Saskia Bock

In this DFG Research Group project we want to make use of the full potential of ThDP-based biocatalysis. The consortium collected in-depth knowledge of the enzymes reaction mechanism and the active sites architecture over the last years. Together with recent insights on optimal reaction- and process parameters, we are now able to rationally design optimised catalysts and apply them for industrially feasible carboligation reactions. In a second part of the project the potential of the recently established ThDP-dependent enzyme database is explored by making use of the possibility to walk through the sequence space and investigate and characterise enzymes in detail.

cooperation partners: Michael Müller (University of Freiburg), Jürgen Pleiss (University of Stuttgart)

funded by:

Logo Deutsche Forschungsgemeinschaft

Grafic Thiamine

DFG Research Group FOR 1296

Application of imine reductases in unconventional media

Postdoctoral project of Dr. Zaira Maugeri

Chiral amines are important building blocks for the synthesis of biologically active pharmaceutical drugs, but their synthesis is challenging. Imine reductases (IREDs) represent a novel class of biocatalysts permitting chiral amine synthesis. In order to enable high substrate concentrations and broaden the substrate scope of these highly potent biocatalysts, the potential of IREDs being operated in unconventional media is investigated.

cooperation partners: Michael Müller (University of Freiburg), Ulf Menyes (Enzymicals AG, Greifswald), Matthias Höhne (University of Greifswald), Hans Iding (F. Hoffmann-La Roche Ltd., CH)

funded by:

Grafic of Helmholtz-Gemeinschaft

Helmholtz Young Investigators Group `Synthetic enzyme cascades´

Industrial scale production of cathine via a synthetic enzyme cascade approach

Postdoctoral project of Dr. Torsten Sehl

Cathine is a pharmaceutically active compound which is sold e.g. on the German market as the main drug in the appetite suppressant ALVALIN®. Since classical synthesis strategies require many steps, lack high yields and/or optical purities, Torsten Sehl investigated a novel biocatalytic 2-step synthesis strategy using ThDP-dependent carboligases and amine transferases in his PhD-thesis. By enzyme engineering and process intensification approaches we now evaluate with our industrial cooperation partner if this enzymatic cascade processes can fulfil industrial requirements even in a large scale pharmaceutical production.

cooperation partners: Ulf Menyes (Enzymicals AG, Greifswald), Martin Erhardt (Herbrand PharmaChemicals GmbH, Gengenbach)

funded by:

Grafic Zentrales Innovationsprogramm Mittelstand


terminated projects


Tailor-made thiamine diphosphate-dependent enzymes for (S)-selective carboligation

PhD-thesis by Robert Westphal

Logo Deutsche Forschungsgemeinschaft

funded by DFG Research Group FOR 1296

selected publication: Westphal R, Vogel C, Schmitz C, Pleiss J, Müller M, Pohl M, Rother D. 2014. A Tailor-made Chimeric Thiamine Enzyme for the Direct Asymmetric Synthesis of (S)-Benzoins. Angew. Chem. Int. Ed. 53 (35): 9376-9379.

Influences of non-conventional media on the selectivity of thiamin-diphosphate (ThDP)-dependent enzymes

PhD-thesis by Tina Gerhards

Logo Deutsche Forschungsgemeinschaft

funded by DFG Research Training Group “Bionoco” GK 11 66
selected publication: Gerhards T, Mackfeld U, Bocola M, von Lieres E, Wiechert W, Pohl M, Rother D. 2012. Influence of organic solvents on enzymatic asymmetric carboligations. Adv. Synth. Catal., 354: 2805-2820.

Stereoselective synthesis of vicinal diols with enzymatic cascade reactions

Logo of Marie Curie Actions

PhD-thesis by Justyna Katarzyna Kulig

funded by Marie-Curie Actions (

selected publications: Kulig J, Frese A, Kroutil W, Pohl M, Rother D. 2013. Biochemical characterization of an alcohol dehydrogenase from Ralstonia sp. Biotech. Bioeng. 110 (7): 1838-1848.

Kulig J, Simon R C, Rose C A, Husain S M, Häckh M, Lüdeke S, Zeitler K, Kroutil W, Pohl M, Rother D. 2012. Stereoselective synthesis of bulky 1,2-diols with alcohol dehydrogenases. Catal. Sci. Technol., 2: 1580-1589.

Development of a biocatalytic production process for (S)-2-hydroxy ketones

Logo of Marie Curie Actions

PhD-thesis by Álvaro Gómez Baraibar

funded by Marie-Curie Actions (

selected publication: Baraibar A G, von Lieres E, Wiechert W, Pohl M, Rother D. 2014. Effective (S)-α-hydroxy ketone production: a reaction engineering approach. Top. Catal. 57: 401-411

2-steps in 1-pot: enzyme cascades for the synthesis of chiral vicinal amino alcohols

Grafic CLIB

PhD-thesis by Torsten Sehl

funded by CLIB Graduate Cluster

selected publications: Sehl T, Hailes H C, Ward J M, Menyes U, Pohl M, Rother D. 2014. Efficient two-step biocatalytic strategies for the synthesis of all nor(pseudo)ephedrine isomers. Green Chem. 16: 3341-3348.

Sehl T, Hailes H C, Ward J M, Wardenga R, von Lieres E, Offermann H, Westphal R, Pohl M, Rother D. 2013. Two Steps in One Pot: Enzyme Cascade for the Synthesis of Nor(pseudo)ephedrine from Inexpensive Starting Materials. Angew. Chem. Int. Ed. 125 (26): 6904-6908.

Synthetic enzyme cascades in micro-aqueous reaction media: using whole cell approaches to obtain high product concentrations

Grafic of Helmholtz-Gemeinschaft

Postdoctoral-project of Dr. Andre Jakoblinnert

funded by Helmholtz Young Investigators Group `Synthetic enzyme cascades´

selected publications: Jakoblinnert A, Rother D. 2014. A two-step biocatalytic cascade in micro-aqueous medium: using whole cells to obtain high concentrations of a vicinal diol. Green Chem. 16: 3472-3482.

Erdmann V, Mackfeld U, Rother D, Jakoblinnert A. 2014. Enantioselective, continuous (R)- and (S)-2-butanol synthesis: achieving high space-time-yields with recombinant E. coli cells in a micro-aqueous, solvent-free reaction system. J. Biotechnol. 191: 106-112.