Biosynthesis of the Active Hypericum perforatum Constituents

Extracts from Hypericum perforatum (St. John’s wort; Clusiaceae) are widely used for the treatment of mild to moderate depression. Four classes of constituents – hyperforins, hypericins, flavonoids, and xanthones – appear to contribute to the antidepressant activity. Interestingly, all four classes of secondary metabolites involve polyketide derivatives. Key reactions of their biosyntheses are catalysed by type III polyketide synthases. These enzymes differ in the starter substrates used, the number of extender units added, and the mode of intramolecular cyclization catalysed. Their products are metabolised by downstream enzymes, such as prenyltransferases and cytochrome P450 enzymes, to give the final active compounds. Despite the medicinal importance of H. perforatum, little is known about the metabolism generating the complex pattern of constituents. _____________________________________________________________________________________________________________