Molecular Cloning and Characterization of a Xanthone Prenyltransferase from Hypericum calycinum Cell Cultures

Abstract

Abstract: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 OPEN ACCESSMolecules 2015, 20 15617 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.

Xanthones and Cancer: from Natural Sources to Mechanisms of Action

“…Most recently isolated xanthones are prenylated (60 %), followed by simple (25 %) and glycosylated (11 %) xanthones ( Figure ). Simple xanthones can commonly be prenylated by aromatic‐prenyltransferase enzymes, which are responsible for linking acetate and/or shikimate to the mevalonate pathway and catalyzing the binding of the isoprene unit . This prenylation is quite usual for the Clusiaceae and Hypericaceae Juss .…”

“…Simple xanthones can commonly be prenylated by aromatic-prenyltransferase enzymes, which are responsible for linking acetate and/or shikimate to the mevalonate pathway and catalyzing the binding of the isoprene unit. [14,15] This prenylation is quite usual for the Clusiaceae and Hypericaceae JUSS. families.…”

Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products

“…Investigation of Hypericum calycinum (Great St. John’s Wort), a source of pharmacologically active specialized metabolites, led to the identification of a membrane-bound aPTase that elaborates xanthone polyketides [17]. This aPTase transfers a 5-carbon dimethylallyl moiety onto 1,2,6,7-tetrahydroxyxanthone to redirect polyketide biosynthesis to tailored natural products such as hyperxanthone E (Figure 1), a compound exhibiting anti-inflammatory properties [18].…”

Exodermis and endodermis are the sites of xanthone biosynthesis in Hypericum perforatum roots

“…Subsequent 3 0 -hydroxylation is catalysed by two bifunctional CYP81AA proteins, which in addition convert the resulting 2,3 0 ,4,6-tetrahydroxybenzophenone to either 1,3,5-or 1,3,7-trihydroxyxanthones via alternative regioselective C-O phenol coupling reactions (El-Awaad et al, 2016). The two trihydroxyxanthone products are likely to be the precursors of all plant xanthones El-Seedi et al, 2010;Fiesel et al, 2015).…”