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The production of hypericins and hyperforin by in vitro cultures of St. John's wort (Hypericum perforatum)

St. John's wort (Hypericum perforatum L.) is a herbaceous perennial distributed throughout the World that has been widely used in traditional medicine. H. perforatum produces several types of biologically active compound, including the hypericins – a family of light‐activated anthraquinones, localized within specialized glands found predominantly on flowers and leaves – and the hyperforins – a family of prenylated acylphloroglucinols localized in the reproductive structures of the plant. Hypericins are known to be toxic to mammals and display antiviral and anticancer activity, but the role of these compounds within the plant is unknown. Hyperforins display potent antimicrobial activity and are thought to be the primary bioactive ingredient for anti‐depressive effects of the herb. The introduction of H. perforatum from Europe into the U.S.A. occurred in the 17th Century. Since the plant is considered a noxious weed, few efforts have been carried out to analyse populations in the context of secondary‐metabolite concentrations. But in terms of secondary‐metabolite studies, H. perforatum is an ideal model system to study the biosyntheses of aromatic polyketides and regulation of those pathways by environmental and genetic influences. This is due, in part, to the ease of conducting these studies in plant tissue culture. This review describes the progress of secondary‐metabolite studies currently underway using H. perforatum. Specifically, this Review focuses on the production and regulation of the hypericins and the hyperforin in wild populations, field cultivation, greenhouse studies and plant tissue culture. Additionally, factors optimizing compound production – particularly in in vitro cultures – are presented and reviewed.