C7A21_PAPSO
ID C7A21_PAPSO Reviewed; 488 AA.
AC I3QBP4; I3PLQ9;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=(S)-canadine synthase CYP719A21 {ECO:0000305};
DE EC=1.14.19.68 {ECO:0000269|PubMed:22653730};
DE AltName: Full=Cytochrome P450 719A21 {ECO:0000303|PubMed:22653730};
GN Name=CYP719A21 {ECO:0000303|PubMed:22653730};
OS Papaver somniferum (Opium poppy).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae; Papaveroideae;
OC Papaver.
OX NCBI_TaxID=3469;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=22527754; DOI=10.1007/s11103-012-9913-2;
RA Desgagne-Penix I., Farrow S.C., Cram D., Nowak J., Facchini P.J.;
RT "Integration of deep transcript and targeted metabolite profiles for eight
RT cultivars of opium poppy.";
RL Plant Mol. Biol. 79:295-313(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=22653730; DOI=10.1126/science.1220757;
RA Winzer T., Gazda V., He Z., Kaminski F., Kern M., Larson T.R., Li Y.,
RA Meade F., Teodor R., Vaistij F.E., Walker C., Bowser T.A., Graham I.A.;
RT "A Papaver somniferum 10-gene cluster for synthesis of the anticancer
RT alkaloid noscapine.";
RL Science 336:1704-1708(2012).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24316226; DOI=10.1016/j.febslet.2013.11.037;
RA Dang T.T., Facchini P.J.;
RT "Cloning and characterization of canadine synthase involved in noscapine
RT biosynthesis in opium poppy.";
RL FEBS Lett. 588:198-204(2014).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27378283; DOI=10.1038/ncomms12137;
RA Li Y., Smolke C.D.;
RT "Engineering biosynthesis of the anticancer alkaloid noscapine in yeast.";
RL Nat. Commun. 7:12137-12137(2016).
RN [5]
RP FUNCTION.
RX PubMed=29610307; DOI=10.1073/pnas.1721469115;
RA Li Y., Li S., Thodey K., Trenchard I., Cravens A., Smolke C.D.;
RT "Complete biosynthesis of noscapine and halogenated alkaloids in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E3922-E3931(2018).
CC -!- FUNCTION: Cytochrome P450 involved in the biosynthesis of the
CC benzylisoquinoline alkaloid noscapine (PubMed:24316226,
CC PubMed:27378283, PubMed:29610307). Converts (S)-tetrahydrocolumbamine
CC to (S)-canadine (PubMed:24316226, PubMed:27378283).
CC {ECO:0000269|PubMed:24316226, ECO:0000269|PubMed:27378283,
CC ECO:0000269|PubMed:29610307}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-tetrahydrocolumbamine + O2 + reduced [NADPH--hemoprotein
CC reductase] = (S)-canadine + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:21456, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16592, ChEBI:CHEBI:17772,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.19.68;
CC Evidence={ECO:0000269|PubMed:24316226, ECO:0000269|PubMed:27378283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21457;
CC Evidence={ECO:0000305|PubMed:24316226};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.63 uM for (S)-tetrahydrocolumbamine
CC {ECO:0000269|PubMed:24316226};
CC Vmax=0.376 pmol/min/mg enzyme with (S)-tetrahydrocolumbamine as
CC substrate {ECO:0000269|PubMed:24316226};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; JQ045709; AFI57927.1; -; mRNA.
DR EMBL; JQ659003; AFB74615.1; -; Genomic_DNA.
DR AlphaFoldDB; I3QBP4; -.
DR SMR; I3QBP4; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0047056; F:(S)-canadine 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:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0033075; P:isoquinoline alkaloid 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 Alkaloid metabolism; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..488
FT /note="(S)-canadine synthase CYP719A21"
FT /id="PRO_0000447599"
FT TRANSMEM 6..26
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|UniProtKB:Q96242"
FT CONFLICT 172..173
FT /note="Missing (in Ref. 2; AFB74615)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="S -> G (in Ref. 2; AFB74615)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="M -> I (in Ref. 2; AFB74615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 55176 MW; 604F195847597C98 CRC64;
MIMSNLWILT LISTILAVFA AVLIIFRRRI SASTTEWPVG PKTLPIIGNL HILGGTALHV
VLHKLAEVYG SVMTIWIGSW KPVIIVSDFD RAWEVLVNKS SDYSAREMPE ITKIGTANWR
TISSSDSGPF WATLRKGLQS VALSPQHLAS QTAHQERDII KLIKNLKDEA ALNSGMVKPL
DHLKKATVRL ISRLIYGQDF DDDKYVEDMH DVIEFLIRIS GYAQLAEVFY YAKYLPSHKR
AVTGAEEAKR RVIALVRPFL QSNPATNTYL HFLKSQLYPE EVIIFAIFEA YLLGVDSTSS
TTAWALAFLI REPSVQEKLY QELKNFTANN NRTMLKVEDV NKLPYLQAVV KETMRMKPIA
PLAIPHKACK DTSLMGKKVD KGTKVMVNIH ALHHTEKVWK EPYKFMPERF LQKHDKAMEQ
SLLPFSAGMR ICAGMELGKL QFSFSLANLV NAFKWSCVSD GVLPDMSDLL GFVLFMKTPL
EARIVPRL
