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Enzyme cascades
We have been developing enzyme cascades (in vitro) to a range of bioactive motifs. These include aminolalcohols and tetrahydroisoquinoline alkaloids (THIAs). For example, THIAs have been accessed using low cost amino acids and newly discovered tyrosinases, decarboxylases to form the required amine substrate and transaminases to produce in situ the highly reactive aldehydes required. By introducing the enzymes at different time-points in the reaction sequence, in one pot reactions and using up to 4 enzymes, cascades have been established to generate new alkaloids including fluorinated analogues (with a collaborator Prof J. M. Ward). As a different approach we have also constructed cascades focusing on the aldehydes required which have been formed using a decarboxylase and transaminase. These reaction cascades are highly innovative and moreover have been extended into 7-enzyme cascades.
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