Extracts of Hypericum perforatum (St. John’s wort) are able to efficiently relieve mild to moderate depression. An important active constituent is hyperforin, the first described PPAP. The compound non-selectively inhibits the reuptake of neurotransmitters from the synaptic cleft into the axoplasm. The target structure is TRPC6. Hyperforin is both a structurally and functionally novel antidepressant. In addition, it possesses further interesting pharmacological properties.
It exhibits anti-bacterial activity against gram-positive bacteria and anti-inflammatory potential. These properties explain the traditional use of St. John’s wort extracts for the local treatment of infected wounds and skin irritations. Another activity is the ability to inhibit the growth of tumour cells by induction of apoptosis. Significantly, this antitumour activity is associated with low acute toxicity in vivo.
The skeleton of hyperforin is formed by a type III polyketide synthase, which uses isobutyryl-CoA as starter substrate. The resulting phlorisobutyrophenone is stepwise prenylated, accompanied by an additional cyclization. The prenyltransferases of interest were identified. The final step of the biosynthesis is a prenylative cyclization. The enzyme involved prenylates the C-3 geranyl group of the last intermediate and catalyzes the cyclization to hyperforin. When the geranyl residue is replaced with a prenyl group, the product is secohyperforin.
A hyperforin-producing root culture line was established. Notably, roots of field-grown plants lack hyperforin. With a productivity of 50 mg/L, the in vitro roots provide a potential production platform. Interestingly, they also accumulate lupulones, the typical constituents of hop, and prenylated xanthones. This is a unique combination of active constituents.