ID   C7BL3_CICIN             Reviewed;         494 AA.
AC   G3GBK0;
DT   03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2011, sequence version 1.
DT   03-AUG-2022, entry version 32.
DE   RecName: Full=Costunolide synthase;
DE            Short=CiCOS;
DE            EC=1.14.14.150 {ECO:0000269|PubMed:21858047};
DE   AltName: Full=Cytochrome P450 71BL3;
GN   Name=CYP71BL3; Synonyms=COS;
OS   Cichorium intybus (Chicory).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; campanulids; Asterales; Asteraceae; Cichorioideae; Cichorieae;
OC   Cichoriinae; Cichorium.
OX   NCBI_TaxID=13427;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=21858047; DOI=10.1371/journal.pone.0023255;
RA   Liu Q., Majdi M., Cankar K., Goedbloed M., Charnikhova T., Verstappen F.W.,
RA   de Vos R.C., Beekwilder J., van der Krol S., Bouwmeester H.J.;
RT   "Reconstitution of the costunolide biosynthetic pathway in yeast and
RT   Nicotiana benthamiana.";
RL   PLoS ONE 6:E23255-E23255(2011).
CC   -!- FUNCTION: Hydroxylates germacrene A acid to 6-alpha-hydroxy-germacrne A
CC       acid, a precursor of sesquiterpene lactones that spontaneously
CC       undergoes a lactonization which yields costunolide. Costunolide can
CC       then spontaneously conjugate to glutathione or cysteine.
CC       {ECO:0000269|PubMed:21858047}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=germacra-1(10),4,11(13)-trien-12-oate + O2 + reduced [NADPH--
CC         hemoprotein reductase] = (+)-costunolide + 2 H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:28230, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:3900, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:61301; EC=1.14.14.150;
CC         Evidence={ECO:0000269|PubMed:21858047};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; JF816041; AEG79727.1; -; mRNA.
DR   AlphaFoldDB; G3GBK0; -.
DR   SMR; G3GBK0; -.
DR   KEGG; ag:AEG79727; -.
DR   BRENDA; 1.14.14.150; 1385.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0102934; F:costunolide synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
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   Transmembrane; Transmembrane helix.
FT   CHAIN           1..494
FT                   /note="Costunolide synthase"
FT                   /id="PRO_0000421932"
FT   TRANSMEM        3..23
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         432
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"
SQ   SEQUENCE   494 AA;  55682 MW;  A4490FC7C21AA14D CRC64;
     MEPLTIVSLV VASLFLFAFW ALSPKTSKNL PPGPPKLPII GNIHQLKSPT PHRVLRNLAR
     KYGPIMHLQL GQVSTVVVST PRLAREIMKT NDISFADRPT TTTSQIFFYK AQDIGWAPYG
     EYWRQMKKIC TLELLSAKKV RSFSSIREEE LSRISKVLES QAGTPINFTE MTVEMVNNVI
     CKATLGDSCK DQATLIEVLY DVLKTLSAFN LASYYPGLQF LNVILGKKAK WLKMQKQLDD
     ILEDVLKEHR SKGSNKSDQE DLVDVLLRVK DTGGLDFTVT DEHVKAVVLD MLTAGTDTSS
     ATLEWAMTEL MRNPHMMKRA QDEVRSVVKG NTITETDLQS LHYLKLIVKE TLRLHAPTPL
     LVPRECRQDC NVDGYDIPAK TKILVNAWAC GTDPDSWKDP ESFIPERFEN CPINYMGADF
     EFIPFGAGRR ICPGLTFGLS MVEYPLANFL YHFDWKLPNG LKPHELDITE ITGISTSLKH
     QLKIVPMIPK SIAK