CP178_ORIVU
ID CP178_ORIVU Reviewed; 496 AA.
AC P0DO35;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 1.
DT 03-AUG-2022, entry version 4.
DE RecName: Full=Cytochrome P450 71D178 {ECO:0000303|Ref.1};
DE AltName: Full=(+)-trans-isopiperitenol synthase {ECO:0000305|Ref.1};
DE EC=1.14.14.- {ECO:0000269|Ref.1};
DE AltName: Full=Carvacrol synthase {ECO:0000305|Ref.1};
DE EC=1.14.14.- {ECO:0000269|Ref.1};
DE AltName: Full=Carveol synthase {ECO:0000305|Ref.1};
DE EC=1.14.14.51 {ECO:0000269|Ref.1};
DE AltName: Full=Gamma-terpinene hydroxylase {ECO:0000305|Ref.1};
DE AltName: Full=Limonene hydroxylase {ECO:0000305|Ref.1};
DE AltName: Full=Thymol synthase {ECO:0000305|Ref.1};
DE EC=1.14.14.- {ECO:0000269|Ref.1};
GN Name=CYP71D178 {ECO:0000303|Ref.1};
OS Origanum vulgare (Wild marjoram).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Origanum.
OX NCBI_TaxID=39352;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=cv. d06-01, and cv. f02-04; TISSUE=Trichome gland;
RA Crocoll C.;
RT "Biosynthesis of the phenolic monoterpenes, thymol and carvacrol, by
RT terpene synthases and cytochrome P450s in oregano and thyme.";
RL Thesis (2011), Friedrich Schiller University of Jena, Germany.
RN [2]
RP REVIEW ON CARVACROL, AND BIOTECHNOLOGY.
RX PubMed=24915411; DOI=10.1080/10408398.2011.653458;
RA Suntres Z.E., Coccimiglio J., Alipour M.;
RT "The bioactivity and toxicological actions of carvacrol.";
RL Crit. Rev. Food Sci. Nutr. 55:304-318(2015).
RN [3]
RP FUNCTION, AND INDUCTION BY MYRMICA ANTS.
RX PubMed=26156773; DOI=10.1098/rspb.2015.1111;
RA Patricelli D., Barbero F., Occhipinti A., Bertea C.M., Bonelli S.,
RA Casacci L.P., Zebelo S.A., Crocoll C., Gershenzon J., Maffei M.E.,
RA Thomas J.A., Balletto E.;
RT "Plant defences against ants provide a pathway to social parasitism in
RT butterflies.";
RL Proc. R. Soc. B 282:0-0(2015).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION BY JASMONIC ACID; SALICYLIC ACID AND
RP UV-C.
RX PubMed=28365519; DOI=10.1016/j.plaphy.2017.03.016;
RA Majdi M., Malekzadeh-Mashhady A., Maroufi A., Crocoll C.;
RT "Tissue-specific gene-expression patterns of genes associated with
RT thymol/carvacrol biosynthesis in thyme (Thymus vulgaris L.) and their
RT differential changes upon treatment with abiotic elicitors.";
RL Plant Physiol. Biochem. 115:152-162(2017).
RN [5]
RP TISSUE SPECIFICITY.
RX DOI=10.1016/j.indcrop.2018.07.006;
RA Jan S., Mir J.I., Shafi W., Faktoo S.Z., Singh D.B., Wijaya L.,
RA Alyemeni M.N., Ahmad P.;
RT "Divergence in tissue-specific expression patterns of genes associated with
RT the terpenoid biosynthesis in two oregano species Origanum vulgare L., and
RT Origanum majorana.";
RL Ind. Crops Prod. 123:546-555(2018).
RN [6]
RP REPRESSION BY SPODOPTERA LITTORALIS.
RX PubMed=30231481; DOI=10.3390/ijms19092805;
RA Agliassa C., Maffei M.E.;
RT "Origanum vulgare Terpenoids Induce Oxidative stress and reduce the feeding
RT activity of Spodoptera littoralis.";
RL Int. J. Mol. Sci. 19:0-0(2018).
RN [7]
RP REVIEW ON THYMOL, AND BIOTECHNOLOGY.
RX PubMed=29785774; DOI=10.1002/ptr.6109;
RA Salehi B., Mishra A.P., Shukla I., Sharifi-Rad M., Contreras M.D.M.,
RA Segura-Carretero A., Fathi H., Nasrabadi N.N., Kobarfard F.,
RA Sharifi-Rad J.;
RT "Thymol, thyme, and other plant sources: Health and potential uses.";
RL Phytother. Res. 32:1688-1706(2018).
RN [8]
RP REVIEW ON CARVACROL AND THYMOL, AND BIOTECHNOLOGY.
RX PubMed=29874939; DOI=10.1080/14786419.2018.1480618;
RA Wang K., Jiang S., Yang Y., Fan L., Su F., Ye M.;
RT "Synthesis and antifungal activity of carvacrol and thymol esters with
RT heteroaromatic carboxylic acids.";
RL Nat. Prod. Res. 33:1924-1930(2019).
RN [9]
RP REVIEW ON CARVACROL EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX PubMed=33664752; DOI=10.3389/fpls.2020.601335;
RA Javed H., Meeran M.F.N., Jha N.K., Ojha S.;
RT "Carvacrol, a plant metabolite targeting viral protease (Mpro) and ACE2 in
RT host cells can be a possible candidate for COVID-19.";
RL Front. Plant Sci. 11:601335-601335(2020).
RN [10]
RP REVIEW ON CARVACROL EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX PubMed=32448034; DOI=10.1080/07391102.2020.1772112;
RA Kumar A., Choudhir G., Shukla S.K., Sharma M., Tyagi P., Bhushan A.,
RA Rathore M.;
RT "Identification of phytochemical inhibitors against main protease of COVID-
RT 19 using molecular modeling approaches.";
RL J. Biomol. Struct. Dyn. 4:1-11(2020).
RN [11]
RP REVIEW ON CARVACROL DERIVATIVES, AND BIOTECHNOLOGY.
RX PubMed=30836858; DOI=10.1080/07391102.2019.1590243;
RA Zengin Kurt B., Durdagi S., Celebi G., Ekhteiari Salmas R., Sonmez F.;
RT "Synthesis, anticholinesterase activity and molecular modeling studies of
RT novel carvacrol-substituted amide derivatives.";
RL J. Biomol. Struct. Dyn. 38:841-859(2020).
RN [12]
RP REVIEW ON PLANT ESSENTIAL OILS EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX PubMed=32834111; DOI=10.1016/j.molstruc.2020.128823;
RA Kulkarni S.A., Nagarajan S.K., Ramesh V., Palaniyandi V., Selvam S.P.,
RA Madhavan T.;
RT "Computational evaluation of major components from plant essential oils as
RT potent inhibitors of SARS-CoV-2 spike protein.";
RL J. Mol. Struct. 1221:128823-128823(2020).
RN [13]
RP REVIEW ON PLANT ESSENTIAL OILS EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX PubMed=33855010; DOI=10.3389/fchem.2021.642026;
RA Yadalam P.K., Varatharajan K., Rajapandian K., Chopra P., Arumuganainar D.,
RA Nagarathnam T., Sohn H., Madhavan T.;
RT "Antiviral essential oil components against SARS-CoV-2 in pre-procedural
RT mouth rinses for dental settings during COVID-19: A computational study.";
RL Front. Chem. 9:642026-642026(2021).
CC -!- FUNCTION: Involved in the biosynthesis of phenolic monoterpenes natural
CC products thymol and carvacrol which have a broad range of biological
CC activities acting as antimicrobial compounds, insecticides,
CC antioxidants and pharmaceutical agents (Ref.1, PubMed:26156773).
CC Catalyzes the C2- and C3-hydroxylation of gamma-terpinene to produce
CC carvacrol and thymol, respectively (Ref.1). Mediates also the C6-
CC hydroxylation of (4S)-limonene to form carveol and the C3-hydroxylation
CC of (4R)-limonene to generate (+)-trans-isopiperitenol (Ref.1).
CC {ECO:0000269|PubMed:26156773, ECO:0000269|Ref.1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (1S,5R)-carveol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17945, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15383, ChEBI:CHEBI:15389, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.51; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17946;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=gamma-terpinene + 2 O2 + 2 reduced [NADPH--hemoprotein
CC reductase] = carvacrol + 2 H(+) + 3 H2O + 2 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:67404, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:3440, ChEBI:CHEBI:10577,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67405;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=gamma-terpinene + 2 O2 + 2 reduced [NADPH--hemoprotein
CC reductase] = 2 H(+) + 3 H2O + 2 oxidized [NADPH--hemoprotein
CC reductase] + thymol; Xref=Rhea:RHEA:67408, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:10577, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27607,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67409;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (1R,6S)-isopiperitenol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:67416, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15382, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:169979; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67417;
CC Evidence={ECO:0000269|Ref.1};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37.2 uM for gamma-terpinene {ECO:0000269|Ref.1};
CC pH dependence:
CC Optimum pH is 6.8-7. {ECO:0000269|Ref.1};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000250|UniProtKB:A0A165U5Z9}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in flowers, leaves and stems, especially
CC in glandular trichomes. {ECO:0000269|PubMed:28365519,
CC ECO:0000269|Ref.5}.
CC -!- INDUCTION: Induced by jasmonic acid (MeJA), salicylic acid (SA) and UV-
CC C irradiation (PubMed:28365519). Accumulates upon root colonization by
CC Myrmica ants (Myrmica sabuleti and Myrmica scabrinodis) concomitantly
CC with jasmonates induction; this leads to the production of carvacrol,
CC an attractant for the phytophagous-predaceous butterfly Maculinea
CC arion, whose larvae initially feed on Origanum vulgare flowerheads
CC before switching to parasitize Myrmica ant colonies for their main
CC period of growth (PubMed:26156773). Slightly repressed by Spodoptera
CC littoralis, an herbivory insect (PubMed:30231481).
CC {ECO:0000269|PubMed:26156773, ECO:0000269|PubMed:28365519,
CC ECO:0000269|PubMed:30231481}.
CC -!- BIOTECHNOLOGY: The monoterpenic phenol thymol is widely used as a
CC fragrance and a flavoring ingredient in food and cosmetic industries
CC (PubMed:29785774). Its derivatives have also several biological and
CC pharmacological properties such as antimicrobial, antioxidant,
CC anticarcinogenesis, anti-inflammatory and antispasmodic activities
CC (PubMed:29785774, PubMed:29874939). Medical applications include the
CC treatment of disorders affecting the respiratory, nervous, and
CC cardiovascular systems (PubMed:29785774). It may also act as a growth
CC enhancer and immunomodulator (PubMed:29785774). Thymol may also have
CC antiviral activity toward COVID-19 by binding to the S1 receptor
CC binding domain of the SARS-CoV-2 spike (S) glycoprotein
CC (PubMed:32834111, PubMed:33855010). {ECO:0000303|PubMed:29785774,
CC ECO:0000303|PubMed:29874939, ECO:0000303|PubMed:32834111,
CC ECO:0000303|PubMed:33855010}.
CC -!- BIOTECHNOLOGY: The monoterpenic phenol carvacrol is commonly used as a
CC fragrance and a food flavoring ingredient and preservative
CC (PubMed:24915411). Its derivatives exhibit also various biological and
CC pharmacological properties including antioxidant, antibacterial,
CC antifungal, insecticid, nematicid, anticancer, anti-inflammatory,
CC hepatoprotective, spasmolytic, and vasorelaxant (PubMed:24915411,
CC PubMed:29874939, PubMed:30836858, PubMed:33664752). Phytochemical
CC inhibitor targeting the main SARS-CoV-2 viral protease (Mpro) and ACE2
CC in human host cells, carvacrol is a possible candidate for treating
CC COVID-19 (PubMed:33664752, PubMed:32448034). Carvacrol may also have
CC antiviral activity toward COVID-19 by binding to the S1 receptor
CC binding domain of the SARS-CoV-2 spike (S) glycoprotein
CC (PubMed:32834111, PubMed:33855010). {ECO:0000303|PubMed:24915411,
CC ECO:0000303|PubMed:29874939, ECO:0000303|PubMed:30836858,
CC ECO:0000303|PubMed:32448034, ECO:0000303|PubMed:32834111,
CC ECO:0000303|PubMed:33664752, ECO:0000303|PubMed:33855010}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR SMR; P0DO35; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0002213; P:defense response to insect; IEP:UniProtKB.
DR GO; GO:0009625; P:response to insect; IEP:UniProtKB.
DR GO; GO:0009753; P:response to jasmonic acid; IEP:UniProtKB.
DR GO; GO:0009751; P:response to salicylic acid; IEP:UniProtKB.
DR GO; GO:0010225; P:response to UV-C; IEP:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..496
FT /note="Cytochrome P450 71D178"
FT /id="PRO_0000453322"
FT TRANSMEM 1..21
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT BINDING 435
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q96242"
SQ SEQUENCE 496 AA; 56091 MW; DEB75F0774428B9E CRC64;
MDISISWVVI ILLVLSYLIL MEKWRAAKLP KNLPPGPPKL PVIGHLHLLG GGLPQHVLRG
ITQKYGPVAH VQLGEVSSVV LSSTEAARQA MKVLDPAFAD RFVNIGSRIM WYDSEDIIFS
RYNDHWRQIR KICVSELLSP KNVKSFGYIR QDEMARLIRL FESSEGAAIN VSEEISKTVC
TIVSRVAFGS VVKDQSLLLN LVKESLRMAS GFELADLFPS SWLLNLLCFN KYRLWGMRRR
LDNFLDGFLE EHRVKKSGEY GGEDIIDVLY RMQKDSQMKV PITNNGIKGF IYDVFSAGTD
TSAATILWAL SELMRNPEKM AKAQAEVREI LKGKTNVDMA EVHELKYLRS VVKEALRLHP
PFPIIPRLCI QESEVTGYTI PANTRILINV WSIGRDPLYW NEPDTFNPDR YDEVPRDIIG
NDFELIPFGS GRRICPGLHF GLANIEVPLA QLLYHFDWKL PQGMTAADID MTEKPGLSGP
RKNPLILVPT IHNPTS
