ID   C719A_PODPE             Reviewed;         489 AA.
AC   L7T720; A0A0F7LUS1;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2021, sequence version 2.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=Pluviatolide synthase {ECO:0000303|PubMed:23161544};
DE            EC=1.14.19.72 {ECO:0000269|PubMed:23161544};
DE   AltName: Full=Cytochrome P450 family 719 subfamily A polypeptide 23 {ECO:0000303|PubMed:23161544};
GN   Name=CYP719A24 {ECO:0000303|PubMed:23161544};
OS   Podophyllum peltatum (American mandrake).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; Ranunculales; Berberidaceae; Podophylloideae;
OC   Podophyllum.
OX   NCBI_TaxID=35933;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOTECHNOLOGY,
RP   PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=23161544; DOI=10.1074/jbc.m112.400689;
RA   Marques J.V., Kim K.-W., Lee C., Costa M.A., May G.D., Crow J.A.,
RA   Davin L.B., Lewis N.G.;
RT   "Next generation sequencing in predicting gene function in podophyllotoxin
RT   biosynthesis.";
RL   J. Biol. Chem. 288:466-479(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 171-433.
RC   STRAIN=cv. LPP1-3, and cv. LPP2-1;
RX   PubMed=25879377; DOI=10.1111/1755-0998.12415;
RA   Mao Y., Zhang Y., Xu C., Qiu Y.;
RT   "Comparative transcriptome resources of two Dysosma species (Berberidaceae)
RT   and molecular evolution of the CYP719A gene in Podophylloideae.";
RL   Mol. Ecol. Resour. 16:228-241(2016).
CC   -!- FUNCTION: Cytochrome P450 involved in the biosynthesis of etoposide, a
CC       chemotherapeutic compound of the topoisomerase inhibitor family
CC       (PubMed:23161544). Catalyzes the conversion of matairesinol to
CC       pluviatolide (PubMed:23161544). {ECO:0000269|PubMed:23161544}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(-)-matairesinol + O2 + reduced [NADPH--hemoprotein reductase]
CC         = (-)-pluviatolide + H(+) + 2 H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:49084, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:6698, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:90896; EC=1.14.19.72;
CC         Evidence={ECO:0000269|PubMed:23161544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49085;
CC         Evidence={ECO:0000269|PubMed:23161544};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q96242};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5.8 uM for (-)-matairesinol {ECO:0000269|PubMed:23161544};
CC         Note=kcat is 7.8 min(-1) with (-)-matairesinol as substrate.
CC         {ECO:0000269|PubMed:23161544};
CC   -!- PATHWAY: Aromatic compound metabolism; phenylpropanoid biosynthesis.
CC       {ECO:0000269|PubMed:23161544}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; KC110998; AGC29954.1; -; mRNA.
DR   EMBL; KP185299; AKH66499.1; -; Genomic_DNA.
DR   EMBL; KP185300; AKH66500.1; -; Genomic_DNA.
DR   AlphaFoldDB; L7T720; -.
DR   SMR; L7T720; -.
DR   KEGG; ag:AGC29954; -.
DR   BioCyc; MetaCyc:MON-19146; -.
DR   BRENDA; 1.14.19.72; 4929.
DR   UniPathway; UPA00711; -.
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:InterPro.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0019438; P:aromatic compound biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0009699; P:phenylpropanoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
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.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..489
FT                   /note="Pluviatolide synthase"
FT                   /id="PRO_0000451902"
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        329
FT                   /note="E -> G (in Ref. 2; AKH66499/AKH66500)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   489 AA;  54244 MW;  2C3B173A80960CBF CRC64;
     MEMETSVLGL SSTLIIALAI TVIFLLKAKS SSAIKWPPGP KTLPIIGNLH QLGGDELHIV
     LAKLARVHGA IMTIWMAKKP VIVVSDVNSV WEVLVSKSSD YAARDAAEIS KIVSASSHSI
     NTSDSGPYWQ TLRRGLTHGP LGPLNISAQI PIQQRDMQRV IREMQQDAAA NGGVIKPLDH
     LKRSSTRLVS RLIFGDTFDN DPYNDSMHEV VQDLNRFGGI ALLEQAFSFA KYLPSYKRGV
     KEFHIHKRKI DDLVRPVVAS SNPPSNSYLG FLQSQNYSEE IIIACIFELY LLAMDSSAST
     ATWALAFMIR DQQVQEKLYQ DIKRVIGDEV GLVKAEDLSK MHYLQAVVKE TMRMKPIAPL
     AIPHKTAIDT SLMGTKVPKG TCVMVNLYAL HHDESVWAKP YTFMPERFLQ REDGKSVTEQ
     AFLPFGAGMR ICGGMEVGKL QFSLALANLV NAFKWTSAAE GKLPDMSDEL QFITVMKTPL
     EARIVPRNP