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Journal of Biomolecules and Biochemistry

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Optimisation of enzymes and chemo-enzymatic processes for the synthesis of pharmaceuticals and fine chemicals

Author(s): Henryk M. Kalisz

 Biocatalysis plays an important role in a wide range of industries, including food and feed, personal care, textiles, detergents, fine chemicals and pharmaceuticals. The increased availability of customised enzymes for use in fine chemical synthesis is making biocatalysis increasingly attractive for the production of chiral pharmaceutical intermediates and APIs, due to the high enantio- and regioselectivity of enzymes, leading to higher yields of the required enantiomer. Consequently, chemo-enzymatic processes are often applied for the synthesis of single enantiomers of drug internediates or APIs. The use of enzymes to replace multi-step complex steps in the synthesis of pharmaceuticals thus helps to reduce the number of steps required to generate the final chiral product and also helps to reduce costs, side products and wastes of the process.

 

The properties of many enzymes used in these processes have been improved by engineering methods. One recent technology used for the engineering of tailor-made enzymes involves the application of a proprietary enzyme design platform overcoming key efficiency bottlenecks in statistical structure-dynamics analysis and enabling the streamlined functional clustering of protein sequence space. This powerful technique allows the fast and reliable identification and subsequent engineering of hotspots in a protein, resulting in a rapid and inexpensive improvement of enzyme properties, such as chirality, catalytic activity, stability, substrate specificity, stereoselectivity. This presentation seeks to provide a description of this enzyme design technology and to provide examples of chemo-enzymatic processes used in the synthesis of pharmaceutical products.


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