A promiscuous prenyltransferase from Aspergillus oryzae catalyses C-prenylations of hydroxynaphthalenes in the presence of different prenyl donors.

Prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily are involved in the biosynthesis of secondary metabolites and show broad substrate specificity towards their aromatic substrates with a high regioselectivity for the prenylation reactions. Most members of this superfamily accepted as prenyl donor exclusively dimethylallyl diphosphate (DMAPP). One enzyme, AnaPT from Neosartorya fischeri, was reported recently to use both DMAPP and geranyl diphosphate (GPP) as prenyl donors. In this study, we demonstrate the acceptance of DMAPP, GPP and farnesyl diphosphate (FPP) by a new member of this superfamily, BAE61387 from Aspergillus oryzae DSM1147, for C-prenylations of hydroxynaphthalenes.

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.

New insights into the biosynthesis of prenylated xanthones: Xptb from Aspergillus nidulans catalyses an O-prenylation of xanthones.

Gene-inactivation experiments have indicated that the putative prenyltransferase XptB from Aspergillus nidulans was likely to be responsible for the prenylation of 1,7-dihydroxy-6-methyl-8-hydroxymethylxanthone. Recently, it was suggested that this enzyme might also accept as substrate the benzophenone arugosin H, which is assumed to be a precursor of prenylated xanthones. In this study, five benzophenones and ten xanthones were incubated with purified recombinant XptB in the presence of dimethylallyl diphosphate (DMAPP). XptB accepted four xanthones as substrates, including the proposed natural substrate, and catalysed regiospecific O-prenylations at C-7 of the xanthone core. K(m) values in the range of 0.081-1.1 mM and turnover numbers (k(cat)) between 0.02 and 0.5 s(-1) were determined for the accepted xanthones. The kinetic parameters for DMAPP were found to be 0.024 mM (K(m)) and 0.13 s(-1) (k(cat)). Arugosin H was not accepted by XptB under the tested conditions. XptB was relatively specific towards its prenyl donor and did not accept geranyl or farnesyl diphosphate as substrate. Mn(2+) and Co(2+) strongly enhanced XptB activity (up to eightfold); this has not been reported before for prenyltransferases of the DMATS superfamily.