Enantiomeric purity is a key determinant of efficacy and safety of modern drugs. The pharmaceutical industry therefore strives for chiral catalysts in process development. A prominent route to introduce chirality is the asymmetric reduction of oxo-containing molecules into chiral alcohols. Exquisite stereoselectivities of reductases increasingly outperform counterpart chemo-catalytic reductions of prochiral ketones, making biocatalysis the method of choice. In general, the biocatalyst employed for ketone reduction can be a whole cell system or a purified protein preparation. The proposed project is a follow up of the Hertha Firnberg-project Harnessing aldo-keto reductases for biocatalysis. We focused on the synthesis of industrially relevant, chiral alcohols by whole cell reduction of the corresponding ketones. The high toxicity of organic substrates, especially those that displayed high hydrophobicity, limited productivity and product yield due to fast catalyst deactivation. Biocatalyst stability is a major concern in virtually all bioprocesses and strategies to address the problem of poor catalyst stability would therefore be important from basic and applied points of view. A detailed study of the impact of hydrophobic substrates on each process level to formulate criteria for an integrated process solution is still missing. This project proposes to address the problem of poor catalyst stability by enhancing performance at the enzyme, cell and process level.
|Effective start/end date||1/07/11 → 30/06/14|