tailieunhanh - Báo cáo khoa học: Thiamin diphosphate in biological chemistry: exploitation of diverse thiamin diphosphate-dependent enzymes for asymmetric chemoenzymatic synthesis

Thiamin diphosphate-dependent enzymes participate in numerous biosyn-thetic pathways and catalyse a broad range of reactions, mainly involving the cleavage and formation of C–C bonds. For example, they catalyse the nonoxidative and oxidative decarboxylation of 2-keto acids, produce 2-hydroxy ketones and transfer activated aldehydes to a variety of acceptors. | MINIREVIEW Thiamin diphosphate in biological chemistry exploitation of diverse thiamin diphosphate-dependent enzymes for asymmetric chemoenzymatic synthesis Michael Muller1 Dorte Gocke2 and Martina Pohl2 1 Institute of PharmaceuticalSciences Albert-Ludwigs-Universitat Freiburg im Breisgau Germany 2 Institute of Molecular Enzyme Technology Heinrich-Heine-Universitat Dusseldorf Julich Germany Keywords 2-hydroxy ketones benzaldehyde lyase benzoin condensation carbon-carbon ligation catalysis pyruvate decarboxylases screening selection stereochemistry thiamin diphosphate chemistry Correspondence M. Muuller Institut fur Pharmazeutische Wissenschaften Albert-Ludwigs-Universitat AlbertstraBe 25 79104 Freiburg im Breisgau Germany Fax 49 761 203 6351 Tel 49 761 203 6320 E-mail . Received 11 January 2009 revised 16 March 2009 accepted 23 March 2009 doi Thiamin diphosphate-dependent enzymes participate in numerous biosynthetic pathways and catalyse a broad range of reactions mainly involving the cleavage and formation of C-C bonds. For example they catalyse the nonoxidative and oxidative decarboxylation of 2-keto acids produce 2-hydroxy ketones and transfer activated aldehydes to a variety of acceptors. Moreover they can also catalyse C-N C-O and C-S bond formation. Because of their substrate spectra and different stereospecificity these enzymes extend the synthetic potential for asymmetric carboligations appreciably. Different strategies have been developed to identify new members of this promiscuous enzyme class and the reactions they catalyse. This enabled us to introduce solutions for longstanding synthetic problems such as asymmetric cross-benzoin condensation. Moreover through a combination of protein structure analysis enzyme and substrate engineering and screening methods we explored additional stereochemical routes that have not been described previously for any of these interesting enzymes. In