Molecular Cloning and Characterization of a Xanthone Prenyltransferase from Hypericum calycinum Cell Cultures.
In plants, prenylation of metabolites is widely distributed to generate compounds with efficient defense potential and distinct pharmacological activities profitable to human health. Prenylated compounds are formed by members of the prenyltransferase (PT) superfamily, which catalyze the addition of prenyl moieties to a variety of acceptor molecules. Cell cultures of Hypericum calycinum respond to elicitor treatment with the accumulation of the prenylated xanthone hyperxanthone E. A cDNA encoding a membrane-bound PT (HcPT) was isolated from a subtracted cDNA library and transcript preparations of H. calycinum. An increase in the HcPT transcript level preceded hyperxanthone E accumulation in cell cultures of H. calycinum treated with elicitor. The HcPT cDNA was functionally characterized by expression in baculovirus-infected insect cells. The recombinant enzyme catalyzed biosynthesis of 1,3,6,7-tetrahydroxy-8-prenylxanthone through regiospecific C-8 prenylation of 1,3,6,7-tetrahydroxyxanthone, indicating its involvement in hyperxanthone E formation. The enzymatic product shared significant structural features with the previously reported cholinesterase inhibitor γ-mangostin. Thus, our findings may offer a chance for semisynthesis of new active agents to be involved in the treatment of Alzheimer's disease.
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. t.fiesel@tu-bs.de.|Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig 38106, Germany. t.fiesel@tu-bs.de.
Tobias
T
Fiesel
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. m.gaid@tu-bs.de.|Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig 38106, Germany. m.gaid@tu-bs.de.
Mariam
M
Gaid
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. der.andreas.mueller@gmx.net.
Andreas
A
Müller
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig 38106, Germany. jo.bartels@tu-bs.de.|Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. jo.bartels@tu-bs.de.
Joana
J
Bartels
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. i.el-awaad@tu-bs.de.
Islam
I
El-Awaad
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. t.beuerle@tu-bs.de.
Till
T
Beuerle
Central NMR Laboratory, Technische Universität Braunschweig, Hagenring 30, Braunschweig 38106, Germany. l.ernst@tu-bs.de.
Ludger
L
Ernst
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig 38106, Germany. s.behrends@tu-bs.de.|Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. s.behrends@tu-bs.de.
Sönke
S
Behrends
Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig 38106, Germany. l.beerhues@tu-bs.de.|Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig 38106, Germany. l.beerhues@tu-bs.de.
Ludger
L
Beerhues
D003001:Cloning, Molecular / Q000379:methods*; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015723:Gene Library; D020902:Hypericum / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044004:Xanthones / Q000378:metabolism
D010940:Plant Proteins; D011994:Recombinant Proteins; D044004:Xanthones; D004122:Dimethylallyltranstransferase
Alzheimer’s disease; Hypericum; aromatic prenyltransferase; membrane-bound enzyme; xanthone