Overview & Research Objectives






  Bioprocess development






  Combination of chemo- and biocatalysis






  Industrial applications






  Protein mass spectrometry
















Overview & Research Objectives


Applied enzyme catalysis (biocatalysis), also nowadays known as "white biotechnology" is considered to represent one of the key technology areas of the 21th century.
In spite of the potential and importance of enzymes as catalysts in organic chemistry, however, the number of efficient industrially applied processes is still limited in comparison to "classic" chemical or chemocatalytic syntheses.
At first, this might surprise when considering the obvious advan-tages of biocatalysis such as high enantio-, diastereo-, regio-, and chemo-selectivity, the use of water as a solvent, and the potential to realize environmentally friendly processes. On the other hand, however, the use of enzymes in organic synthesis is still often limited, e.g., by the incompatibility of enzymes with an organic solvent environment, narrow substrate range as well as the typical separation of biocatalytic reactions from "classic chemical" types of reactions. Overcoming these limitations represents a major challenge in biocatalysis in order to fully benefit from the tremendous catalytic potential of enzymes and to develop efficient, environmentally friendly and technically feasible organic synthetic transformations.

The research activities of the Gröger group has been centering since many years around the application of enzymes as valuable and environmental friendly catalysts in organic synthetic transformations.
A particular goal of the highly interdisciplinary research projects has been the development of synthetic processes which fulfil the criteria of high efficiency, sustainability as well as scalability. To realize such processes the focus of the Gröger teams has been on (1) the development of efficient biocatalytic reactions (biotransformations) and technical applications thereof, (2) the combination of biocatalysis with chemocatalysis in one-pot multi-step syntheses, and (3) industrial applications based on the use of biocatalysts in synthetic key steps (in particular for the synthesis of pharmaceuticals).
A key feature of the research activities in the Gröger group at the interface between biology and organic chemistry has been the high degree of interdisciplinarity, underlined by numerous collaborations with academic and industrial partners.
The research work of Gröger and his teams has been awarded, e.g., Degussa Innovation Awards [in 2003 (category: new products) and 2005 (category: new or improved processes)]. Furthermore, in 2008 Gröger was awarded the Carl-Duisberg-Memorial Prize of the German Chemical Society (GDCh).

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Bioprocess development


In the research area of biocatalytic process development (bioprocess development) Gröger and his teams (in industry until 2006, at in academia since 2006) developed successfully many new biocatalytic processes applying, e.g., innovative biocatalyst concepts.
Notably, within these interdisciplinary projects jointly with collaboration partners several biocatalytic processes running on industrial scale have been realized (see also section below about industrial applications). A particular highlight is the developed highly efficient asymmetric biocatalytic reduction and reductive amination technology based on the use of recombinant whole cell catalysts. Both types of processes run at high substrate loading of typically >100 g/L and give the desired products with >99% ee.
Recently, jointly with collaboration partners new biocatalytic processes have been developed based on the use of enoate reductases (for C= C-reduction) and L-threonine aldolases (for aldol reactions).
For selected key publications from Gröger and his teams in this area of bioprocess development, see for example references [1]-[3].

[1] Angew. Chem. 2006, 118, 5806-5809; Angew. Chem. Int. Ed. 2006, 45, 1645-1648.
[2] Angew. Chem. 2006, 118, 1676-1679; Angew. Chem. Int. Ed. 2006, 45, 5677-5681.
[3] Angew. Chem. 2013, 125, in press; Angew. Chem. Int. Ed. 2013, 52, in press. top



Combination of chemo- and biocatalysis


A further research highlight is the successful development of various chemoenzymatic one-pot multi-step processes.
In particular, we have been interested to use water as a solvent since - besides representing a non-toxic, cheap and readily available solvent - water enables the use of the full range of enzymes as catalysts in such processes. In our pioneer work in this field, "classic" chemical reactions, metal-catalyzed reactions and organocatalytic reactions, respectively, have been combined with enzymatic transformations, leading to the formation of the desired products in an efficient fashion and with excellent enantioselectivity.
These research achievements underline that such combinations of the two "worlds of catalysis", chemocatalysis and biocatalysis, are possible, enabling advantageous synthetic processes, which avoid solvent-intensive and waste-generating process steps.
For selected key publications from the Gröger group in this area of chemoenzymatic one-pot synthesis on water, see for example references [4]-[7].

[4] Angew. Chem. 2008, 120, 9693-9696; Angew. Chem. Int. Ed. 2008, 47, 9551-9554.
[5] Angew. Chem. 2009, 121, 9519-9522; Angew. Chem. Int. Ed. 2009, 48, 9355-9358.
[6] Angew. Chem. 2011, 123, 2445-2448; Angew. Chem. Int. Ed. 2011, 50, 2397-2400.
[7] Angew. Chem. 2011, 123, 8092-8095; Angew. Chem. Int. Ed. 2011, 50, 7944-7947. top



Industrial applications


From an early stage on we have been interested to combine basic research with industrial applications.
As outlined above, jointly with collaboration partners several biocatalytic processes running on industrial scale have been developed by Gröger and his teams. Successful industrial applications of biocatalysts in organic synthetic processes have been realized, e.g., for the enantioselective synthesis of chiral key building blocks, in particular pharmaceutically relevant molecules.[9-10]
By means of various biotransformations as key steps (comprising hydrolytic as well as redox reactions), synthetic approaches towards non-natural α-amino acids, β-amino acids and alcohols have been realized on technical scale.

[9] Speciality Chemicals Magazine 2004, (5), 24-25.
[10] Enzyme Catalysis in Organic Synthesis (eds.: K. Drauz, H. Gröger, O. May), 3. ed., Wiley-VCH, Weinheim, 2012. top



Protein mass spectrometry


Biocatalysis requires powerful enzymes in order to achieve optimal results. However, enzymes isolated from wild-type organisms may not be able to be used to their full potential under conditions necessary for biocatalysis.
Accordingly, the preferred form of an efficient biocatalyst is typically the recombinant form of an enzyme, which is overexpressed in a suitable host organism such as E. coli. En route to such recombinant forms of biocatalysts, novel promising enzymes isolated from natural sources needs to be characterized after their isolation and purification by determing their amino acids sequence and, e.g., their cofactor binding.
This aim will be addressed by employing proteomic approaches using mass spectrometry.


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