The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum Perforatum L., One of the Largest Medicinal Crops in Europe.

Paride Rizzo,Twan Rutten,John C D'Auria,Beena M Ravindran,Lothar Altschmied

doi:10.3390/genes11101210

Paride Rizzo, Twan Rutten + Show 3 more

Open Access

https://doi.org/10.3390/genes11101210

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Abstract

Hypericum perforatum L. commonly known as Saint John’s Wort (SJW), is an important medicinal plant that has been used for more than 2000 years. Although H. perforatum 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.

Highlights

Hypericum perforatum (Figure 1) belongs to the order Malpighales, which includes more than16,000 species
A realistic perspective for the large scale production of bioactive compounds in Saint John’s Wort (SJW) should rely on the biosynthesis genes, as well as on the genes involved in the differentiation of dark glands (AGL6, MYB38), and the translocation and secretion mechanisms (GST)
Hypericum research has experienced a resurgence of scientific interest due to the newly discovered potential of its bioactives, and their abilities to be utilized as an anticancer medicine and a possible treatment for neurodegenerative diseases

Summary

Introduction

Hypericum perforatum (Figure 1) belongs to the order Malpighales, which includes more than. SJW extracts are the main source of natural hypericin This naphtodianthrone is regarded as an efficient anticancer compound that induces an apoptotic response after binding to melanoma cancer cells [28]. Interest in SJW extracts has gone beyond the antidepressant, anti-cancer and antiviral applications after it was discovered that these extracts can reduce both memory impairment and β-amyloid fibril deposition in the brain of APP-transgenic mice [10] These results are compliant with in vitro studies showing that hypericin can interfere and significantly inhibit the formation of β-amyloid fibrils by associating with the precursors of these fibrils [42,43]. Rats treated with SJW extracts showed an increased expression of the ABCC1 transporter which is involved in the clearance of brain tissues from the β-amyloid plaques [10] Since this effect is independent of hyperforin it suggests an additional role for hypericin [10]. By maintaining maintaining mitochondrial transmembrane electric potential, the overload of calcium uptake in the mitochondrial transmembrane electric potential, the overload of calcium uptake in the mitochondrion mitochondrion is avoided [47]. is avoided [47]

Secretory

The Frontier of Dark Gland and Hypericin Biosynthesis Research

Hypericin Biosynthesis

Hyperforin

Findings

Conclusions