Enzyme Catalysis in Organic Synthesis
Our interdisciplinary research activities at the interface between biology and organic chemistry focus on the application of enzymes as catalysts in synthetic reactions. A particular goal is the development of synthetic processes fulfilling the criteria of high efficiency, sustainability and scalability.
Prof. Dr. Harald Gröger
Previous and Current Research
Applied enzyme catalysis (biocatalysis), also nowadays known as “white biotechnology” is considered to be 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 advantages of biocatalysis such as high enantio-, diastereo-, regio-, and chemo-selectivity, the use of water as a reaction medium, 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 organic solvents, narrow substrate range and 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 reactions.
In the research area of bioprocess development Gröger and his teams (in industry until 2006, at the University of Erlangen-Nürnberg from 2006 to 2011 and at Bielefeld University since 2011) developed successfully many new biocatalytic processes. Within these interdisciplinary projects jointly with collaboration 63partners several processes running on industrial scale have been realized. A representative highlight is the developed 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), P450-monooxygenases (for hydroxylation) and L-threonine aldolases (for aldol reactions). A further research highlight is the successful development of various chemoenzymatic one-pot multi-step processes in water by combining “classic” chemical reactions, metal-catalyzed reactions and organocatalytic reactions, respectively, with enzymatic transformations. The desired products are formed in an efficient fashion and with excellent enantioselectivity, underlining that such types of combinations of the two “worlds of catalysis”, chemocatalysis and biocatalysis, are possible. Such combinations enable advantageous synthetic processes, thus avoiding solvent-intensive and waste-generating work-up steps. Furthermore, we could successfully apply biocatalysts in the enantioselective (multi-step) synthesis of pharmaceutically relevant molecules such as non-natural α-amino acids, β-amino acid derivatives and specific chiral alcohols.
Future Projects and Aims
Among major current challenges are the development of efficient biocatalytic oxidation and C-C bond forming processes as well as the development of novel chemoenzymatic one-pot processes in water by, e.g., combining three or more synthetic steps. In addition, a further focus is on novel retrosynthetic approaches towards pharmaceutically relevant molecules based on the use of enzymatic key steps.