Biocatalysis Development: Ered Assay Development and Naphthol Synthesis
Ene-reductases (EREDs) of the flavin dependent Old Yellow Enzyme (OYE) family catalyse the formal trans addition of molecular hydrogen to activated C=C bonds and have found applications in the synthesis of chiral synthons for the pharmaceutical industry. This is achieved by delivery of a proton to Cα, via a structurally conserved Tyr residue and hydride delivery to Cβ, from reduced FMN. Typically, the hydride is derived from a nicotinamide cofactor but alternative hydride sources, in the form of sacrificial co-substrates, have been well studied.
In the current study, a fluorescence-based assay was developed for the detection of 2-naphthol during the ERED-catalysed reduction of a model substrate. This facile assay was applied to Almac’s in-house panel of EREDs revealing a range of activities, including many promising hits. Several of these hit enzymes were then challenged with a panel of substituted tetralones, resulting in the efficient production of the equivalent naphthols derived from tetralones 1-8.
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