Angelicin

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Jong Seong Kang - One of the best experts on this subject based on the ideXlab platform.

Frederic Bourgaud - One of the best experts on this subject based on the ideXlab platform.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2009
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and-4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of ()-colum-bianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K m of 2.1 0.4 M for ()-columbianetin and a k cat of 112 14 min 1. Moreover, the use of 3-deuterated ()-columbianetin as substrate led to an almost complete " metabolic switch, " resulting in the synthesis of anti-3-hydroxy-3-deuterated()-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution. Furanocoumarins are natural plant metabolites characterized by a furane moiety fused to benzopyran-2-one. The position of the furane substitution distinguishes two large groups of compounds, the linear (psoralens) and the angular furanocou-marins (Angelicin and derivatives) (Fig.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2008
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and -4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of (+)-columbianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K(m) of 2.1 +/- 0.4 microm for (+)-columbianetin and a k(cat) of 112 +/- 14 min(-1). Moreover, the use of 3'-deuterated (+)-columbianetin as substrate led to an almost complete "metabolic switch," resulting in the synthesis of anti-3'-hydroxy-3'-deuterated(+)-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3'. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution.

  • Molecular Cloning and Functional Characterization of Psoralen Synthase, the First Committed Monooxygenase of Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2007
    Co-Authors: Romain Larbat, Frederic Bourgaud, Alain Hehn, Joachim Hans, Sandra Kellner, Silvia Specker, Eric Gontier, Ulrich Matern
    Abstract:

    Ammi majus L. accumulates linear furanocoumarins by cyto-chrome P450 (CYP)-dependent conversion of 6-prenylumbellif-erone via ()-marmesin to psoralen. Relevant activities, i.e. pso-ralen synthase, are induced rapidly from negligible background levels upon elicitation of A. majus cultures with transient maxima at 9 –10 h and were recovered in labile microsomes. Expressed sequence tags were cloned from elicited Ammi cells by a nested DD-RT-PCR strategy with CYP-specific primers, and full-size cDNAs were generated from those fragments correlated in abundance with the induction profile of furanocou-marin-specific activities. One of these cDNAs representing a transcript of maximal abundance at 4 h of elicitation was assigned CYP71AJ1. Functional expression in Escherichia coli or yeast cells initially failed but was accomplished eventually in yeast cells after swapping the N-terminal membrane anchor domain with that of CYP73A1. The recombinant enzyme was identified as psoralen synthase with narrow substrate specificity for ()-marmesin. Psoralen synthase catalyzes a unique carbon-chain cleavage reaction concomitantly releasing acetone by syn-elimination. Related plants, i.e. Heracleum mantegazzianum, are known to produce both linear and angular furanocoumarins by analogous conversion of 8-prenylumbelliferone via ()-columbianetin to Angelicin, and it was suggested that Angelicin synthase has evolved from psoralen synthase. However, ()-columbianetin failed as sub-strate but competitively inhibited psoralen synthase activity. Analogy modeling and docked solutions defined the conditions for high affinity substrate binding and predicted the minimal requirements to accommodate ()-columbianetin in the active site cavity. The studies suggested that several point mutations are necessary to pave the road toward Angelicin synthase evolution.

  • Furocoumarins and other secondary metabolites from Psoralea canescens
    International Journal of Pharmacognosy, 1997
    Co-Authors: Gabbriella Innocenti, Anna Piovan, Frederic Bourgaud, Donata Favretto
    Abstract:

    The furocoumarin and other chemical constituents from Psoralea canescens, a perennial legume from North America, were investigated. Two furocoumarins, psoralen and its angular isomer, Angelicin, and two other major components (propenoic acid derivatives) were isolated and identified by spectroscopic methods. P. canescens contains furocoumarins in both free and bound forms. The psoralen/Angelicin ratios show that psoralen is predominant in all plant organs. Furocoumarins were shown to accumulate mainly in the roots, smaller amounts being present in the flowers and immature fruits. Considering the good dry matter production of Psoralea canescens, this species appears to be a valuable natural source of furocoumarins.

  • A selective photobiological assay to detect and quantify psoralen in Psoralea plants (Leguminosae)
    Phytochemical Analysis, 1994
    Co-Authors: Frederic Bourgaud, J. Y. Grimal, Christophe Nguyen, G. Bitton, Armand Guckert
    Abstract:

    A simple and rapid bioassay involving the gram-positive bacterium Bacillus brevis was developed to detect and quantify furocoumarins (psoralen and Angelicin) in Psoralea plants (Leguminosae). Small paper discs, soaked with furocoumarin standards or the corresponding plant samples, are placed on B. brevis lawns in Petri dishes and irradiated for 24 h with UVA. The diameter of the growth inhibition zone around the discs is very well-correlated with the quantity of furocoumarin standard in the disc. Because psoralen is more phototoxic than Angelicin, its detection limit (5 × 10−8 g/disc) was lower than Angelicin (5 × 10−7 g/disc). Consequently, it is possible to dilute a crude plant extract in order to reach a detectable psoralen concentration whilst maintaining the Angelicin concentration below its lower detection limit. In this condition, Angelicin does not interfer with psoralen detection, and the growth inhibition is entirely due to psoralen. The bioassay was validated using a classical high pressure liquid chromatographic method and the correlation between the two techniques was satisfactory with plant samples. Therefore, the bioassay can be considered as a sensitive, simple, rapid and selective method to quantify psoralen in Psoralea plants.

Ulrich Matern - One of the best experts on this subject based on the ideXlab platform.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2009
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and-4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of ()-colum-bianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K m of 2.1 0.4 M for ()-columbianetin and a k cat of 112 14 min 1. Moreover, the use of 3-deuterated ()-columbianetin as substrate led to an almost complete " metabolic switch, " resulting in the synthesis of anti-3-hydroxy-3-deuterated()-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution. Furanocoumarins are natural plant metabolites characterized by a furane moiety fused to benzopyran-2-one. The position of the furane substitution distinguishes two large groups of compounds, the linear (psoralens) and the angular furanocou-marins (Angelicin and derivatives) (Fig.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2008
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and -4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of (+)-columbianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K(m) of 2.1 +/- 0.4 microm for (+)-columbianetin and a k(cat) of 112 +/- 14 min(-1). Moreover, the use of 3'-deuterated (+)-columbianetin as substrate led to an almost complete "metabolic switch," resulting in the synthesis of anti-3'-hydroxy-3'-deuterated(+)-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3'. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution.

  • Molecular Cloning and Functional Characterization of Psoralen Synthase, the First Committed Monooxygenase of Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2007
    Co-Authors: Romain Larbat, Frederic Bourgaud, Alain Hehn, Joachim Hans, Sandra Kellner, Silvia Specker, Eric Gontier, Ulrich Matern
    Abstract:

    Ammi majus L. accumulates linear furanocoumarins by cyto-chrome P450 (CYP)-dependent conversion of 6-prenylumbellif-erone via ()-marmesin to psoralen. Relevant activities, i.e. pso-ralen synthase, are induced rapidly from negligible background levels upon elicitation of A. majus cultures with transient maxima at 9 –10 h and were recovered in labile microsomes. Expressed sequence tags were cloned from elicited Ammi cells by a nested DD-RT-PCR strategy with CYP-specific primers, and full-size cDNAs were generated from those fragments correlated in abundance with the induction profile of furanocou-marin-specific activities. One of these cDNAs representing a transcript of maximal abundance at 4 h of elicitation was assigned CYP71AJ1. Functional expression in Escherichia coli or yeast cells initially failed but was accomplished eventually in yeast cells after swapping the N-terminal membrane anchor domain with that of CYP73A1. The recombinant enzyme was identified as psoralen synthase with narrow substrate specificity for ()-marmesin. Psoralen synthase catalyzes a unique carbon-chain cleavage reaction concomitantly releasing acetone by syn-elimination. Related plants, i.e. Heracleum mantegazzianum, are known to produce both linear and angular furanocoumarins by analogous conversion of 8-prenylumbelliferone via ()-columbianetin to Angelicin, and it was suggested that Angelicin synthase has evolved from psoralen synthase. However, ()-columbianetin failed as sub-strate but competitively inhibited psoralen synthase activity. Analogy modeling and docked solutions defined the conditions for high affinity substrate binding and predicted the minimal requirements to accommodate ()-columbianetin in the active site cavity. The studies suggested that several point mutations are necessary to pave the road toward Angelicin synthase evolution.

Fang Geng - One of the best experts on this subject based on the ideXlab platform.

  • protctive effects of Angelicin on uvb induced hdf cells damage and its mechanism
    Traditional Chinese Medicine, 2018
    Co-Authors: Juncen Liu, Haiyang Liu, Guoliang Liu, Yueying Wang, Hainan Gao, Fang Geng
    Abstract:

    Objective To study the effect of Angelicin on proliferation activity and anti-aging related protein expression of human HDF cells and its mechanism. Methods According to the random number table method, the cells were divided into blank group, model group, estradiol group, Angelicin group, estrogen receptor antagonist+estradiol group, estrogen receptor antagonist+Angelicin group, and P38 pathway blocker group. Different groups were given the according drugs respectively for 24 h. Except the blank group, all the groups of cells were given UVB irradiation with a dose of 150 mJ/cm2. The MTT assay was used to detect cell proliferation rate. The Western blot was used to detect the expression levels of COLⅠ, MMP-1, ERβ, P38 and p-P38 in cells, and the MMP-1 mRNA expression was detected by real-time fluorescent quantitative PCR. Results Compared with the model group, the proliferation rate of HDF cells significantly increased in Angelicin (10, 1, 0.1 and 0.01 μmol/L groups) (P<0.01); The protein expression of COLⅠ (0.326 ± 0.006 vs. 0.176 ± 0.007), ERβ (0.281 ± 0.011 vs. 0.143 ± 0.006) significantly increased (P<0.01), and the expression of MMP-1 (0.256 ± 0.006 vs. 0.395 ± 0.006) and p-P38 (0.224 ± 0.003 vs. 0.318 ± 0.005) significantly decreased (P<0.01) in Angelicin 10 μmol/L group. Compared with 10 μmol/L Angelicin group, the protein expression of estrogen receptor antagonist+Angelicin group ERβ (0.120 ± 0.007 vs. 0.281 ± 0.011) significantly decreased and MMP-1mRNA (1.377 ± 0.012 vs. 1.024 ± 0.010) significantly increased (P<0.01). Conclusions The Angelicin may degrade MMP-1 through the ER-P38 MAPK signaling pathway,and then promote collagen synthesis, to achieve the purpose of prevention and treatment of photoaging. Key words: Angelicin; Estrogen receptor beta; p38 mitogen-activated protein kinases; Collagen; Matrix metalloproteinases; Skin aging

  • Protctive effects of Angelicin on UVB-induced HDF cells damage and its mechanism
    Traditional Chinese Medicine, 2018
    Co-Authors: Juncen Liu, Haiyang Liu, Guoliang Liu, Yueying Wang, Hainan Gao, Fang Geng
    Abstract:

    Objective To study the effect of Angelicin on proliferation activity and anti-aging related protein expression of human HDF cells and its mechanism. Methods According to the random number table method, the cells were divided into blank group, model group, estradiol group, Angelicin group, estrogen receptor antagonist+estradiol group, estrogen receptor antagonist+Angelicin group, and P38 pathway blocker group. Different groups were given the according drugs respectively for 24 h. Except the blank group, all the groups of cells were given UVB irradiation with a dose of 150 mJ/cm2. The MTT assay was used to detect cell proliferation rate. The Western blot was used to detect the expression levels of COLⅠ, MMP-1, ERβ, P38 and p-P38 in cells, and the MMP-1 mRNA expression was detected by real-time fluorescent quantitative PCR. Results Compared with the model group, the proliferation rate of HDF cells significantly increased in Angelicin (10, 1, 0.1 and 0.01 μmol/L groups) (P

Romain Larbat - One of the best experts on this subject based on the ideXlab platform.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2009
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and-4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of ()-colum-bianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K m of 2.1 0.4 M for ()-columbianetin and a k cat of 112 14 min 1. Moreover, the use of 3-deuterated ()-columbianetin as substrate led to an almost complete " metabolic switch, " resulting in the synthesis of anti-3-hydroxy-3-deuterated()-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution. Furanocoumarins are natural plant metabolites characterized by a furane moiety fused to benzopyran-2-one. The position of the furane substitution distinguishes two large groups of compounds, the linear (psoralens) and the angular furanocou-marins (Angelicin and derivatives) (Fig.

  • Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2008
    Co-Authors: Romain Larbat, Alain Hehn, Joachim Hans, Sarah Schneider, Hélène Jugdé, Bernd Schneider, Ulrich Matern, Frederic Bourgaud
    Abstract:

    The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and -4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of (+)-columbianetin to Angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The Angelicin synthase exhibited an apparent K(m) of 2.1 +/- 0.4 microm for (+)-columbianetin and a k(cat) of 112 +/- 14 min(-1). Moreover, the use of 3'-deuterated (+)-columbianetin as substrate led to an almost complete "metabolic switch," resulting in the synthesis of anti-3'-hydroxy-3'-deuterated(+)-columbianetin. This confirms that Angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3'. Sequence comparison between psoralen synthase (CYP71AJ3) and Angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution.

  • Molecular Cloning and Functional Characterization of Psoralen Synthase, the First Committed Monooxygenase of Furanocoumarin Biosynthesis
    Journal of Biological Chemistry, 2007
    Co-Authors: Romain Larbat, Frederic Bourgaud, Alain Hehn, Joachim Hans, Sandra Kellner, Silvia Specker, Eric Gontier, Ulrich Matern
    Abstract:

    Ammi majus L. accumulates linear furanocoumarins by cyto-chrome P450 (CYP)-dependent conversion of 6-prenylumbellif-erone via ()-marmesin to psoralen. Relevant activities, i.e. pso-ralen synthase, are induced rapidly from negligible background levels upon elicitation of A. majus cultures with transient maxima at 9 –10 h and were recovered in labile microsomes. Expressed sequence tags were cloned from elicited Ammi cells by a nested DD-RT-PCR strategy with CYP-specific primers, and full-size cDNAs were generated from those fragments correlated in abundance with the induction profile of furanocou-marin-specific activities. One of these cDNAs representing a transcript of maximal abundance at 4 h of elicitation was assigned CYP71AJ1. Functional expression in Escherichia coli or yeast cells initially failed but was accomplished eventually in yeast cells after swapping the N-terminal membrane anchor domain with that of CYP73A1. The recombinant enzyme was identified as psoralen synthase with narrow substrate specificity for ()-marmesin. Psoralen synthase catalyzes a unique carbon-chain cleavage reaction concomitantly releasing acetone by syn-elimination. Related plants, i.e. Heracleum mantegazzianum, are known to produce both linear and angular furanocoumarins by analogous conversion of 8-prenylumbelliferone via ()-columbianetin to Angelicin, and it was suggested that Angelicin synthase has evolved from psoralen synthase. However, ()-columbianetin failed as sub-strate but competitively inhibited psoralen synthase activity. Analogy modeling and docked solutions defined the conditions for high affinity substrate binding and predicted the minimal requirements to accommodate ()-columbianetin in the active site cavity. The studies suggested that several point mutations are necessary to pave the road toward Angelicin synthase evolution.