Biosynthesis of Psoralen: Mechanism of a Cytochrome P450 Catalyzed Oxidative Bond Cleavage

Stanjek, Volker; Miksch, Martin; Lueer, Patricia; Matern, Ulrich; Boland, Wilhelm

doi:10.1002/(sici)1521-3773(19990201)38:3<400::aid-anie400>3.3.co;2-b

Cited by 12 publications

(13 citation statements)

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“…(A) Proposed biosynthetic route to phloroglucinol moiety and acyl side chain in the skeleton (summarized from Adam, Arigoni, Bacher, & Eisenreich, 2002; Karppinen, Hokkanen, Tolonen, Mattila, & Hohtola, 2007; Klinglauf et al, 2005). (B) Proposed biosynthetic elaboration upon the skeleton, leading to acylphloroglucinols isolated from H. empetrifolium (HE), Hypericum jovis (HJ) (compound numbering from Athanasas et al, 2004) and Hypericum amblycalyx (HA) (compound numbering from Winkelmann et al, 2003) (Boubakir, Beuerle, Liu, & Beerhues, 2005; Stanjek, Miksch, Lueer, Matern, & Boland, 1999). …”

Section: Figmentioning

confidence: 99%

Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium

Crockett

Wenzig

Kunert

et al. 2008

Phytochemistry Letters

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Phytochemical investigation of Hypericum empetrifolium Willd. (Clusiaceae), a species native to Greece and Turkey has led to the bioassay-guided identification of two acylphloroglucinol derivatives with potent in vitro anti-inflammatory activity. Using NMR spectroscopy and mass spectrometry, the acylphloroglucinol derivatives were characterized as 3-geranyl-1-(2'-methylpropanoyl)phloroglucinol (1) and 3-geranyl-1-(2'-methylbutanoyl)phloroglucinol (2). Hypotheses are proposed regarding the biosynthetic origin of these and similar acylphloroglucinols from related Hypericum species. Compounds 1 and 2 were evaluated for in vitro inhibitory activity against COX-1, COX-2 and 5-LOX catalyzed LTB(4) formation. Compound 1 displayed good activity (IC(50) values: 6.0, 29.9, and 2.2 μM, respectively) in all three assays. Compound 2 showed good activity (IC(50) value: 5.8 μM) against LTB(4) formation and moderate activity (IC(50) value: 26.2 μM) against COX-1.

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Section: Figmentioning

confidence: 99%

Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium

Crockett

Wenzig

Kunert

et al. 2008

Phytochemistry Letters

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“…1 ). Both enzymes catalyze the same kind of reaction, cleaving the C-C bond at the C-3’ position forming the furanocoumarin skeleton and acetone in equimolar amounts [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution of substrate recognition sites (SRSs) in cytochromes P450 from Apiaceae exemplified by the CYP71AJ subfamily

et al. 2015

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BackgroundLarge proliferations of cytochrome P450 encoding genes resulting from gene duplications can be termed as ‘blooms’, providing genetic material for the genesis and evolution of biosynthetic pathways. Furanocoumarins are allelochemicals produced by many of the species in Apiaceaous plants belonging to the Apioideae subfamily of Apiaceae and have been described as being involved in the defence reaction against phytophageous insects.ResultsA bloom in the cytochromes P450 CYP71AJ subfamily has been identified, showing at least 2 clades and 6 subclades within the CYP71AJ subfamily. Two of the subclades were functionally assigned to the biosynthesis of furanocoumarins. Six substrate recognition sites (SRS1-6) important for the enzymatic conversion were investigated in the described cytochromes P450 and display significant variability within the CYP71AJ subfamily. Homology models underline a significant modification of the accession to the iron atom, which might explain the difference of the substrate specificity between the cytochromes P450 restricted to furanocoumarins as substrates and the orphan CYP71AJ.ConclusionTwo subclades functionally assigned to the biosynthesis of furanocoumarins and four other subclades were identified and shown to be part of two distinct clades within the CYP71AJ subfamily. The subclades show significant variability within their substrate recognition sites between the clades, suggesting different biochemical functions and providing insights into the evolution of cytochrome P450 ‘blooms’ in response to environmental pressures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0396-z) contains supplementary material, which is available to authorized users.

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“…Furanocoumarin is one of the best‐studied plant coumarins. Extensive studies of furanocoumarin biosynthesis have shown that several cytochrome P450 mono‐oxygenases (P450s) are involved in the hydroxylation steps after prenylation at the 6‐ or 8‐position of umbelliferone (7‐hydroxycoumarin; Hamerski and Matern, 1988a,b; Stanjek and Boland, 1998; Stanjek et al. , 1999).…”

Section: Introductionmentioning

confidence: 99%

Scopoletin is biosynthesized viaortho‐hydroxylation of feruloyl CoA by a 2‐oxoglutarate‐dependent dioxygenase inArabidopsis thaliana

et al. 2008

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SummaryCoumarins are derived via the phenylpropanoid pathway in plants. The 2H-1-benzopyran-2-one core structure of coumarins is formed via the ortho-hydroxylation of cinnamates, trans/cis isomerization of the side chain, and lactonization. Ortho-hydroxylation is a key step in coumarin biosynthesis as a branch point from lignin biosynthesis; however, ortho-hydroxylation of cinnamates is not yet fully understood. In this study, scopoletin biosynthesis was explored using Arabidopsis thaliana, which accumulates scopoletin and its b-glucopyranoside scopolin in its roots. T-DNA insertion mutants of caffeoyl CoA O-methyltransferase 1 (CCoAOMT1) showed significant reduction in scopoletin and scopolin levels in the roots, and recombinant CCoAOMT1 exhibited 3¢-O-methyltransferase activity on caffeoyl CoA to feruloyl CoA. These results suggest that feruloyl CoA is a key precursor in scopoletin biosynthesis. Ortho-hydroxylases of cinnamates were explored in the oxygenase families in A. thaliana, and one of the candidate genes in the Fe(II)-and 2-oxoglutaratedependent dioxygenase (2OGD) family was designated as F6¢H1. T-DNA insertion mutants of F6¢H1 showed severe reductions in scopoletin and scopolin levels in the roots. The pattern of F6¢H1 expression is consistent with the patterns of scopoletin and scopolin accumulation. The recombinant F6¢H1 protein exhibited orthohydroxylase activity for feruloyl CoA (K m = 36.0 AE 4.27 lM; k cat = 11.0 AE 0.45 sec )1 ) to form 6¢-hydroxyferuloylCoA, but did not hydroxylate ferulic acid. These results indicate that Fe(II)-and 2-oxoglutarate-dependent dioxygenase is the pivotal enzyme in the ortho-hydroxylation of feruloyl CoA in scopoletin biosynthesis.

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Biosynthesis of Psoralen: Mechanism of a Cytochrome P450 Catalyzed Oxidative Bond Cleavage

Cited by 12 publications

References 0 publications

Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium

Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium

Evolution of substrate recognition sites (SRSs) in cytochromes P450 from Apiaceae exemplified by the CYP71AJ subfamily

Scopoletin is biosynthesized viaortho‐hydroxylation of feruloyl CoA by a 2‐oxoglutarate‐dependent dioxygenase inArabidopsis thaliana

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