Biotechnological approaches for the production of hypericin and other important metabolites from the genus Hypericum

Hypericin, a polycyclic naphthodianthrone and active plant pigment with the molecular formula C₃₀H₁₆O₈, is a crucial phytochemical extracted from the dark-colored glands present on the aerial parts of the genus Hypericum. It is biosynthesized through the polyketide pathway by plant-specific type III polyketide synthases (PKSs). In addition to hypericin, the genus Hypericum is rich in various classes of phytochemicals. Alongside other bioactive compounds like hyperforin and flavonoids, hypericin exhibits antidepressant activity. Recently, hypericin has gained increased importance in the research due to its unique properties. Its photodynamic nature makes it an effective natural photosensitizer, extending its use in investigating skin disorders. Moreover, hypericin demonstrates antiviral and antitumoral properties. Despite its effectiveness in treating cancers and neurological disorders, hypericin production faces challenges due to its site-specific nature. Conventional methods struggle to meet the growing demand for hypericin. Biotechnological approaches, including plant tissue culture and bioreactor-based large-scale production, offer promising solutions to address this demand. This review focuses on various plant tissue culture techniques, such as cell and organ culture, and elucidates their biosynthetic pathways. It also discusses hypericin production using elicitation strategies involving biotic and abiotic components, as well as genetic engineering approaches to enhance hypericin yields. Bioreactor-scale production presents significant potential for sustainable hypericin production. Further advancements in understanding and engineering biosynthetic pathways hold promise for unlocking new avenues in hypericin production.