| Summary: | <i>Hypericum perforatum</i> L. commonly known as Saint John’s Wort (SJW), is an important medicinal plant that has been used for more than 2000 years. Although <i>H. perforatum</i> produces several bioactive compounds, its importance is mainly linked to two molecules highly relevant for the pharmaceutical industry: the prenylated phloroglucinol hyperforin and the naphtodianthrone hypericin. The first functions as a natural antidepressant while the second is regarded as a powerful anticancer drug and as a useful compound for the treatment of Alzheimer’s disease. While the antidepressant activity of SJW extracts motivate a multi-billion dollar industry around the world, the scientific interest centers around the biosynthetic pathways of hyperforin and hypericin and their medical applications. Here, we focus on what is known about these processes and evaluate the possibilities of combining state of the art omics, genome editing, and synthetic biology to unlock applications that would be of great value for the pharmaceutical and medical industries.
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