Biosynthesis of polyprenylated xanthones in Hypericum perforatum roots involves 4-prenyltransferase

Author:

Sayed Hesham M B123ORCID,Nassar Sara124ORCID,Kaufholdt David5ORCID,Beerhues Ludger12ORCID,Liu Benye12ORCID,El-Awaad Islam123ORCID

Affiliation:

1. Institute of Pharmaceutical Biology, Technische Universität Braunschweig , Braunschweig 38106 , Germany

2. Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig , Braunschweig 38106 , Germany

3. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University , Assiut 71526 , Egypt

4. Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University , Cairo 11566 , Egypt

5. Institute of Plant Biology, Technische Universität Braunschweig , Braunschweig 38106 , Germany

Abstract

Abstract Polyprenylated xanthones are natural products with a multitude of biological and pharmacological activities. However, their biosynthetic pathway is not completely understood. In this study, metabolic profiling revealed the presence of 4-prenylated 1,3,5,6-tetrahydroxyxanthone derivatives in St. John's wort (Hypericum perforatum) root extracts. Transcriptomic data mining led to the detection of 5 variants of xanthone 4-prenyltransferase (HpPT4px) comprising 4 long variants (HpPT4px-v1 to HpPT4px-v4) and 1 short variant (HpPT4px-sh). The full-length sequences of all 5 variants were cloned and heterologously expressed in yeast (Saccharomyces cerevisiae). Microsomes containing HpPT4px-v2, HpPT4px-v4, and HpPT4px-sh catalyzed the addition of a prenyl group at the C-4 position of 1,3,5,6-tetrahydroxyxanthone; 1,3,5-trihydroxyxanthone; and 1,3,7-trihydroxyxanthone, whereas microsomes harboring HpPT4px-v1 and HpPT4px-v3 additionally accepted 1,3,6,7-tetrahydroxyxanthone. HpPT4px-v1 produced in Nicotiana benthamiana displayed the same activity as in yeast, while HpPT4px-sh was inactive. The kinetic parameters of HpPT4px-v1 and HpPT4px-sh chosen as representative variants indicated 1,3,5,6-tetrahydroxyxanthone as the preferred acceptor substrate, rationalizing that HpPT4px catalyzes the first prenylation step in the biosynthesis of polyprenylated xanthones in H. perforatum. Dimethylallyl pyrophosphate was the exclusive prenyl donor. Expression of the HpPT4px transcripts was highest in roots and leaves, raising the question of product translocation. C-terminal yellow fluorescent protein fusion of HpPT4px-v1 localized to the envelope of chloroplasts in N. benthamiana leaves, whereas short, truncated, and masked signal peptides led to the disruption of plastidial localization. These findings pave the way for a better understanding of the prenylation of xanthones in plants and the identification of additional xanthone-specific prenyltransferases.

Funder

German Egyptian Research Long-Term Scholarship

Egyptian Ministry of Higher Education

Deutscher Akademischer Austauschdienst

Deutsche Forschungsgemeinschaft

Publisher

Oxford University Press (OUP)

Subject

Plant Science,Genetics,Physiology

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