CP180_ORIVU
ID CP180_ORIVU Reviewed; 496 AA.
AC P0DO39;
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 71D180 {ECO:0000303|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 EC=1.14.14.53 {ECO:0000269|Ref.1};
DE AltName: Full=Gamma-terpinene hydroxylase {ECO:0000305|Ref.1};
DE AltName: Full=Limonene hydroxylase {ECO:0000305|Ref.1};
GN Name=CYP71D180 {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, PATHWAY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=cv. Ct; TISSUE=Leaf;
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 INDUCTION BY DROUGHT.
RX PubMed=27915173; DOI=10.1016/j.plaphy.2016.11.023;
RA Morshedloo M.R., Craker L.E., Salami A., Nazeri V., Sang H., Maggi F.;
RT "Effect of prolonged water stress on essential oil content, compositions
RT and gene expression patterns of mono- and sesquiterpene synthesis in two
RT oregano (Origanum vulgare L.) subspecies.";
RL Plant Physiol. Biochem. 111:119-128(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 FUNCTION, AND INDUCTION 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:30231481,
CC PubMed:26156773). Catalyzes the C2-hydroxylation of gamma-terpinene to
CC produce carvacrol (Ref.1). Mediates also the C6-hydroxylation of (4S)-
CC limonene and (4R)-limonene to form carveol (Ref.1).
CC {ECO:0000269|PubMed:26156773, ECO:0000269|PubMed:30231481,
CC 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=(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=(4R)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (1R,5S)-carveol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:18957, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15382, ChEBI:CHEBI:15388, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.53; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18958;
CC Evidence={ECO:0000269|Ref.1};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|Ref.1}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Mostly expressed in flowers and stems, and, to a
CC lower extent, in leaves. {ECO:0000269|Ref.5}.
CC -!- INDUCTION: Induced by drought (PubMed:27915173). Accumulates upon root
CC colonization by Myrmica ants (Myrmica sabuleti and Myrmica scabrinodis)
CC concomitantly with jasmonates induction; this leads to the production
CC of carvacrol, an attractant for the phytophagous-predaceous butterfly
CC Maculinea arion, whose larvae initially feed on Origanum vulgare
CC flowerheads before switching to parasitize Myrmica ant colonies for
CC their main period of growth (PubMed:26156773). Strongly induced by
CC Spodoptera littoralis, an herbivory insect, thus triggering the
CC production of carvacrol, which exhibits insecticide properties
CC (PubMed:30231481). {ECO:0000269|PubMed:26156773,
CC ECO:0000269|PubMed:27915173, 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; P0DO39; -.
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:0009414; P:response to water deprivation; 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 71D180"
FT /id="PRO_0000453326"
FT TRANSMEM 1..21
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT REGION 471..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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; 55734 MW; 624D5D312245CB0A CRC64;
MDISISWVVI IVFVLSYLIL MDKWRASKLP GNLPPSPPKL PVIGHLHLLR GGLPQHVLRG
ITQKYGAVAH LQLGEVHSVV LSSAESTKQA MKVLDPTFAD RFDSIGSQIM WYNNDDMIFS
RYNDHWRQIR KICVSELLSP RNVRSFGFIR QDEMARLIRV FESSEGAAIN ASEEISKMSC
AIVCRAAFGS VLKDQGKLAD LVKEALSMAS GFELADLYPS SWLLNLLCVN KYRLQRMRGR
LDNILDGFLE EHKVKKSGEF GGEDIVDVLY RMQKDTEMKA PITNNGIKGF IFDVFSAGTE
TSATTIQWAL SELMKNPEKM VKAQAEVREK LKGKTNPDVA DVQELKYLHS VVKETLRLHP
PFPLIPRLCK EECEVTGYTI PAKTRTLVNV WSIGRDPAYW KDPDTFNPDR FDEVSRDVIG
NDFELIPFGA GRRVCPGLHF GLANVEVPLA QLLYHFDYKL PSAMTAADMD MSETPGLSGP
RKNPLIMIPT IHNPTS
