The first prenylation step in hyperforin biosynthesis

Prenylation reactions contribute considerably to the diversity of natural products. Polyprenylated secondary metabolites include hyperforin which is both quantitatively and pharmacologically a major constituent of the medicinal plant Hypericum perforatum (St. John's wort). Cell cultures of the related species Hypericum calycinum were found to contain a prenyltransferase activity which is likely to catalyze the first prenylation step in hyperforin biosynthesis. The enzyme was soluble and dependent on a divalent cation, with Fe2+ leading to maximum activity (K-m = 3.8 mM). The preferred prenyl donor was DMAPP (K-m = 0.46 mM) and the preferred prenyl acceptor was phlorisobutyrophenone (K-m = 0.52 mM). A broad pH optimum from 6.5 to 8.5 and a temperature optimum from 35 to 40 degreesC were observed. The formation of hyperforins in H. calycinum cell cultures was preceded by an increase in dimethylallyltransferase activity, with the maximum specific activity being 3.6 mukat/kg protein. (C) 2004 Elsevier Ltd. All rights reserved.