Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis

El‐Awaad, Islam; Bocola, Marco; Beuerle, Till; Liu, Benye; Beerhues, Ludger

doi:10.1038/ncomms11472

Cited by 52 publications

(51 citation statements)

References 69 publications

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“…Group 2 included Unigene51020 showing close phylogenetic relationship with CYP81AA1-Hc. CYP81AA1-Hc has been shown to catalyze 3′-hydroxylation of 2,4,6-trihydroxybenzophenone and subsequently C-O phenol coupling to synthesize 2,3′,4,6-tetrahydroxybenzophenone [39]. Group 3 included three unigenes phylogenetically related to CYP76A3-Ph, which has been shown to catalyze ω-hydroxylation of myristic acid [40].…”

Section: Assemblermentioning

confidence: 99%

De Novo Transcriptome Assembly and Characterization of Lithospermum officinale to Discover Putative Genes Involved in Specialized Metabolites Biosynthesis

et al. 2018

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is a valuable source of bioactive metabolites with medicinal and industrial values. However, little is known about genes involved in the biosynthesis of these metabolites, primarily due to the lack of genome or transcriptome resources. This study presents the first effort to establish and characterize transcriptome assembly resource for and expression analysis for three of its tissues, namely leaf, stem, and root. Using over 4Gbps of RNA-sequencing datasets, we obtained transcriptome assembly of, consisting of 77,047 unigenes with assembly N50 value as 1524 bps. Based on transcriptome annotation and functional classification, 52,766 unigenes were assigned with putative genes functions, gene ontology terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. KEGG pathway and gene ontology enrichment analysis using highly expressed unigenes across three tissues and targeted metabolome analysis showed active secondary metabolic processes enriched specifically in the root of . Using co-expression analysis, we also identified 20 and 48 unigenes representing different enzymes of lithospermic/chlorogenic acid and shikonin biosynthesis pathways, respectively. We further identified 15 candidate unigenes annotated as cytochrome P450 with the highest expression in the root of as novel genes with a role in key biochemical reactions toward shikonin biosynthesis. Thus, through this study, we not only generated a high-quality genomic resource for but also propose candidate genes to be involved in shikonin biosynthesis pathways for further functional characterization.

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Section: Assemblermentioning

confidence: 99%

De Novo Transcriptome Assembly and Characterization of Lithospermum officinale to Discover Putative Genes Involved in Specialized Metabolites Biosynthesis

et al. 2018

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“…Mangostins are tropical plants, of which xanthones are important secondary metabolites 18 . As an aprenylated xanthone derivative of mangosteen, α-mangostin (α-m) has been shown to possess a variety of pharmacological properties, including anti-inflammatory, neuroprotective and anticancer effects 19 – 23 .…”

Section: Introductionmentioning

confidence: 99%

Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways

et al. 2020

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Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of −1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.

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“…1). 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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Xanthones are specialized metabolites with antimicrobial properties, which accumulate in roots of Hypericum perforatum. This medicinal plant provides widely taken remedies for depressive episodes and skin disorders. Owing to the array of pharmacological activities, xanthone derivatives attract attention for drug design. Little is known about the sites of biosynthesis and accumulation of xanthones in roots. Xanthone biosynthesis is localized at the transcript, protein, and product levels using in situ mRNA hybridization, indirect immunofluorescence detection, and high lateral and mass resolution mass spectrometry imaging (AP-SMALDI-FT-Orbitrap MSI), respectively. The carbon skeleton of xanthones is formed by benzophenone synthase (BPS), for which a cDNA was cloned from root cultures of H. perforatum var. angustifolium. Both the BPS protein and the BPS transcripts are localized to the exodermis and the endodermis of roots. The xanthone compounds as the BPS products are detected in the same tissues. The exodermis and the endodermis, which are the outermost and innermost cell layers of the root cortex, respectively, are not only highly specialized barriers for controlling the passage of water and solutes but also preformed lines of defence against soilborne pathogens and predators.

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Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis

Cited by 52 publications

References 69 publications

De Novo Transcriptome Assembly and Characterization of Lithospermum officinale to Discover Putative Genes Involved in Specialized Metabolites Biosynthesis

De Novo Transcriptome Assembly and Characterization of Lithospermum officinale to Discover Putative Genes Involved in Specialized Metabolites Biosynthesis

Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways

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

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