title: Biotechnological production of hyperforin for pharmaceutical formulation.
abstract: Hyperforin is a major active constituent of Hypericum perforatum (St. John's wort). It has amazing pharmacological activities, such as antidepressant properties, but it is labile and difficult to synthesize. Its sensitivity and lipophilicity are challenges for processing and formulation. Its chemical complexity provokes approaches of biotechnological production and modification. Dedifferentiated H. perforatum cell cultures lack appropriate storage sites and hence appreciable hyperforin levels. Shoot cultures are capable of forming hyperforin but less suitable for biomass up-scaling in bioreactors. Roots commonly lack hyperforin but a recently established adventitious root line has been demonstrated to produce hyperforin and derivatives at promising levels. The roots also contained lupulones, the typical constituents of hop (Humulus lupulus). Although shear-sensitive, these root cultures provide a potential production platform for both individual compounds and extracts with novel combinations of constituents and pharmacological activities. Besides in vitro cultivation techniques, the reconstruction of hyperforin biosynthesis in microorganisms is a promising alternative for biotechnological production. The biosynthetic pathway is under study, with omics-technologies being increasingly implemented. These biotechnological approaches may not only yield hyperforin at reasonable productivity but also allow for modifications of its chemical structure and pharmacological profile.
authors.affiliation: Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Mariam
authors.initials: M
authors.lastname: Gaid
authors.affiliation: Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Eline
authors.initials: E
authors.lastname: Biedermann
authors.affiliation: Institute of Pharmaceutical Technology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Jendrik
authors.initials: J
authors.lastname: Füller
authors.affiliation: Institute of Chemical and Thermal Process Engineering, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Haas
authors.affiliation: Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Behrends
authors.affiliation: Institute of Biochemical Engineering, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Krull
authors.affiliation: Institute of Chemical and Thermal Process Engineering, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Scholl
authors.affiliation: Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Wittstock
authors.affiliation: Institute of Pharmaceutical Technology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Müller-Goymann
authors.affiliation: Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Germany; Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Germany. Electronic address: l.beerhues@tu-bs.de.
authors.forename: Ludger
authors.initials: L
authors.lastname: Beerhues
mesh_terms: D001709:Biotechnology; D004339:Drug Compounding / Q000379:methods*; D020902:Hypericum; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000302:isolation & purification; D018517:Plant Roots; D013678:Technology, Pharmaceutical / Q000379:methods*; D013729:Terpenes / Q000138:chemical synthesis* / Q000302:isolation & purification
chemical_list: D010936:Plant Extracts; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin
keywords: Formulations; Gene identification; Heterologous production; Hyperforin; Hypericin; Hypericum perforatum; In vitro cultures; Pharmacological profile; Root cultures; Stabilization