Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608308
Lecture Session – Biosynthesis & Sustainable Use & YRW Award Lectures
Georg Thieme Verlag KG Stuttgart · New York

Successive xanthone prenylation in Hypericum sampsonii

M Nagia
1   Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig, Germany
2   Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig, Germany
,
M Gaid
1   Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig, Germany
2   Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig, Germany
,
T Beuerle
1   Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig, Germany
,
L Beerhues
1   Institute of Pharmaceutical Biology, Technische Universität Braunschweig, Mendelssohnstraße 1, Braunschweig, Germany
2   Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35 A, Braunschweig, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 
 

    Hypericum species exhibit affluence of bioactive polyprenylated metabolites derived from various chemical nuclei including acyl- and benzoylphloroglucinol, flavonoid and xanthone [1]. Prenylated xanthones receive special attention due to their biological impact on human health. Their biosynthesis is achieved through two stages, (i) formation of the xanthone nucleus, (ii) decoration by side chains. Aromatic prenyltransferases catalyse the introduction of prenyl groups to an electron-rich aromatic substrate. Metabolic profiling of Hypericum sampsonii, whose extracts are used in TCM to treat swellings, burns, backache and in Taiwan as antitumor drug, showed abundance of pharmacologically active prenylated xanthones. Patulone inhibits the exogenous platelet activating factor, induces hypotension in mice, and inhibits COX-1 enzyme [2]. Hypericumxanthones [3] and Hyperixanthone A [4] are antibacterial metabolites from H. sampsonii.

    This work presents the complete elucidation of the biosynthetic pathway of patulone. Two prenyltransferases from H. sampsonii, which are responsible for the decoration of 1,3,6,7-tetrahydroxyxanthone to produce patulone, were studied at the gene level. Constructs of pECS-URA harbouring the individual genes were created for yeast expression. Activity screening of the recombinant proteins against potential substrates from different chemical classes revealed their narrow substrate specificity, the strict regiospecificity to C-8 of the 1,3,6,7-tetrahydroxyxanthone skeleton and absolute dependence on Mg2+ ions. The sequential prenylation of 1,3,6,7-tetrahydroxyxanthone was proved through determination of the kinetic parameters. The product of HsPT8PX is used as substrate for HsPTpat to form the gem-diprenylated patulone. When fused to YFP, both enzymes showed subcellular localization to chloroplasts. Our results inaugurate a novel chemo-enzymatic production approach for pharmacologically important trace natural products.

    Zoom Image
    Fig. 1: Successive xanthone prenylation in Hypericum sampsonii

    [1] Avato, P. A Survey on the Hypericum Genus. Elsevier; 2005: 603 – 634.

    [2] Yamakuni, T, et al, Neurosci. Lett, 2006; 394: 206 – 210.

    [3] Xin, W.-B, et al, Phytotherapy Res, 2011; 25: 536 – 539.

    [4] Xiao, Z.Y, et al, Pharmaceut. Biol, 2008; 46: 250 – 253.


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    Zoom Image
    Fig. 1: Successive xanthone prenylation in Hypericum sampsonii