Substrate Requirements for Lepidopteran Farnesol Dehydrogenase

Farnesol dehydrogenase of the lepidopteran Manduca sexta shows surprisingly high substrate specificity, as inferred from the binding of substrate analogs and (potential) alternative substrates. The enzyme is not a simple alcohol dehydrogenase, as ethanol and octanol are not substrates for this enzyme. The enzyme also does not appear to be related to Drosophila alcohol dehydrogenase since secondary alcohols are much poorer inhibitors. Several farnesol analogs with modified carbon skeletons have been tested for their ability to function as inhibitors of farnesol dehydrogenase. Substrate competition studies indicate that the enzyme is highly specific for alcohols with delta-2,3 unsaturation, trans allylic olefin geometry, and alkyl chain hydrophobicity corresponding to at least three isoprene units. These results suggest that farnesol dehydrogenase is a unique dehydrogenase that should be further examined as a potential target for anti juvenoid development