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Technische Universiteit Delft

The Biocatalysis and Organic Chemistry group in Delft will contribute to WP3, WP5 and WP6. In particular the change of the enzyme activity/enzyme promiscuity will be a topic of investigation. This will be explored in the context of multienzyme cascade reactions. We intend to focus on the change of enzyme activity in the lipases towards hydroxynitrile lyases. Considering high structural similarity it is widely accepted that several hydroxynitrile lyases (such as those from Hevea brasiliensis and Manihot esculenta) and lipases have derived from a common ancestor. Although their catalytic site consists of a catalytic triade virtually identical to that of lipases, hydroxynitrile lyases display no hydrolase activity. Instead they catalyse the formation of a carbon carbon bond, the formation of a cyanohydrin. Detailed bioinformatics analysis including identification of evolutionary relationship, positional genomics, metabolic reconstruction, analysis of regulation and other bioinformatics-based comparative techniques should strongly improve the prediction of mutations leading to lipase promisquity. This should open up an entirely new pool of carbon carbon bond forming enzymes, namely modified lipases. These will be tested in biocatalytic cascade reactions. Here we think of an in situ biocatalytic oxidation of an alcohol and subsequent enantioselective addition of HCN catalysed by the newly developed enzymes.
The group will contribute their long standing expertise in biocatalysis and organic chemistry. Over the years many contributions to hydroxynitrile lyase-catalysed reactions have been made. Furthermore dynamic kinetic resolutions as a tool to prepare enantiopure cyanohydrins were developed. The chemical and more recently the selective enzyme-catalysed oxidation of alcohols is a focus of attention in the group. In addition the newly established molecular biotechnology laboratory and production of mutant enzymes will form a vital part of this project.
enzym
IRENE is a project funded by the European Commission under the Seventh Framework Programme
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