Geranylation of cyclic dipeptides by the dimethylallyl transferase AnaPT resulting in a shift of prenylation position on the indole ring.

The dimethylallyl transferase AnaPT from Neosartorya fischeri is involved in the biosynthesis of acetylaszonalenin and catalyses the regioselective and stereospecific C3α-prenylation of (R)-benzodiazepinedione in the presence of dimethylallyl diphosphate. This enzyme also converts several tryptophan-containing cyclic dipeptides to C3α-prenylated indolines. In this study, we demonstrate the geranylation of (R)-benzodiazepinedione and five other cyclic dipeptides by AnaPT in the presence of geranyl diphosphate (GPP). Interestingly, structure elucidation by NMR and MS analyses revealed that, with GPP, the geranyl moiety is attached to C-6 or C-7 rather than C-3 of the indole ring of the enzyme products. For (R)-benzodiazepinedione, one dominant C6-geranylated derivative was obtained, whereas the other five substrates yielded both C6- and C7-geranylated products. Neither acceptance of GPP by a dimethylallyl transferase from the dimethylallyltryptophan synthase superfamily, nor the alkylation shift from C-3 to the benzene ring of the indole nucleus has been reported previously.