CP180_THYVU
ID CP180_THYVU Reviewed; 496 AA.
AC P0DO38;
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 Thymus vulgaris (Thyme).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Thymus.
OX NCBI_TaxID=49992;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=cv. T28, and cv. Tc; TISSUE=Leaf, and 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 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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
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). Catalyzes the C2-
CC hydroxylation of gamma-terpinene to produce carvacrol (Ref.1). Mediates
CC also the C6-hydroxylation of (4S)-limonene and (4R)-limonene to form
CC carveol (Ref.1). {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 -!- 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40.3 uM for gamma-terpinene {ECO:0000269|Ref.1};
CC KM=14.1 uM for (4R)-limonene {ECO:0000269|Ref.1};
CC KM=0.11 uM for (4S)-limonene {ECO:0000269|Ref.1};
CC Note=kcat is 1.24 sec(-1) with gamma-terpinene as substrate (Ref.1).
CC kcat is 0.08 sec(-1) with (4R)-limonene as substrate (Ref.1). kcat is
CC 0.15 sec(-1) with (4S)-limonene as substrate (Ref.1).
CC {ECO:0000269|Ref.1};
CC pH dependence:
CC Optimum pH is 6.4-6.8. {ECO:0000269|Ref.1};
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, to a lower extent,
CC in leaves, especially in glandular trichomes.
CC {ECO:0000269|PubMed:28365519}.
CC -!- INDUCTION: Induced by jasmonic acid (MeJA), salicylic acid (SA) and UV-
CC C irradiation. {ECO:0000269|PubMed:28365519}.
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; P0DO38; -.
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: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 71D180"
FT /id="PRO_0000453325"
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"
FT VARIANT 156
FT /note="R -> C (in strain: cv. Tc)"
FT /evidence="ECO:0000305|Ref.1"
FT VARIANT 229
FT /note="F -> V (in strain: cv. Tc)"
FT /evidence="ECO:0000305|Ref.1"
FT VARIANT 266
FT /note="I -> V (in strain: cv. Tc)"
FT /evidence="ECO:0000305|Ref.1"
FT VARIANT 386
FT /note="I -> T (in strain: cv. Tc)"
FT /evidence="ECO:0000305|Ref.1"
SQ SEQUENCE 496 AA; 55809 MW; F19F0F3C474581B3 CRC64;
MDISISWVVI IVFVLSYLIL MDKWRASKLP GNLPPSPPKL PVIGHLHLLR GGLPQHVLRG
ITQKYGAVAH LQLGEVHSVV LSSAESTKQA MKVLDPTFAD RFDSIGSQIM WYNNDDMIFS
RYNDHWRQIR KICVSELLSP RNVRSFGFIR QDEMARLIRV FESSEGAAIN ASEEISKMSC
AIVCRAAFGS VLKDQGKLAD LVKEALSMAS GFELADLYPS SWLLNLLCFN KYRLQRMRGR
LDNILDGFLE EHKVKKSGEF GGEDIIDVLY RMQKDTEMKA PITNNGIKGF IFDVFSAGTE
TSATTIQWAL SELMKNPEKM VKAQAEVREK LKGKTNPDVA DVQELKYLHS VVKETLRLHP
PFPLIPRLCK EECEVTGYTI PAKTRILVNV WSIGRDPAYW KDPDTFNPDR FDEVSRDVIG
NDFELIPFGA GRRVCPGLHF GLANVEVPLA QLLYHFDYKL PSAMTAADMD MSETPGLSGP
RKNPLIMIPT IHNPTS
