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Thiamin diphosphate in biological chemistry: exploitation of diverse thiamin diphosphate‐dependent enzymes for asymmetric chemoenzymatic synthesis
Author(s) -
Müller Michael,
Gocke Dörte,
Pohl Martina
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07017.x
Subject(s) - chemistry , enzyme , decarboxylation , biocatalysis , stereospecificity , stereochemistry , substrate (aquarium) , oxidative decarboxylation , bond cleavage , combinatorial chemistry , organic chemistry , catalysis , reaction mechanism , oceanography , geology
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.