C719A_SINHE
ID C719A_SINHE Reviewed; 489 AA.
AC L7T8H2;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Pluviatolide synthase {ECO:0000303|PubMed:23161544};
DE EC=1.14.19.72 {ECO:0000269|PubMed:23161544, ECO:0000269|PubMed:26359402};
DE AltName: Full=Cytochrome P450 family 719 subfamily A polypeptide 23 {ECO:0000303|PubMed:23161544};
GN Name=CYP719A23 {ECO:0000303|PubMed:23161544};
GN Synonyms=Phex30934 {ECO:0000303|PubMed:26359402};
OS Sinopodophyllum hexandrum (Himalayan may apple) (Podophyllum hexandrum).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; Ranunculales; Berberidaceae; Podophylloideae;
OC Sinopodophyllum.
OX NCBI_TaxID=93608;
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 FUNCTION, CATALYTIC ACTIVITY, BIOTECHNOLOGY, TISSUE SPECIFICITY, INDUCTION
RP BY WOUNDING, AND PATHWAY.
RX PubMed=26359402; DOI=10.1126/science.aac7202;
RA Lau W., Sattely E.S.;
RT "Six enzymes from mayapple that complete the biosynthetic pathway to the
RT etoposide aglycone.";
RL Science 349:1224-1228(2015).
CC -!- FUNCTION: Cytochrome P450 involved in the biosynthesis of etoposide, a
CC chemotherapeutic compound of the topoisomerase inhibitor family
CC (PubMed:23161544, PubMed:26359402). Catalyzes the conversion of
CC matairesinol to pluviatolide (PubMed:23161544, PubMed:26359402).
CC {ECO:0000269|PubMed:23161544, ECO:0000269|PubMed:26359402}.
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, ECO:0000269|PubMed:26359402};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49085;
CC Evidence={ECO:0000269|PubMed:23161544, ECO:0000269|PubMed:26359402};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.7 uM for (-)-matairesinol {ECO:0000269|PubMed:23161544};
CC Note=kcat is 14.9 min(-1) with (-)-matairesinol as substrate.
CC {ECO:0000269|PubMed:23161544};
CC -!- PATHWAY: Aromatic compound metabolism; phenylpropanoid biosynthesis.
CC {ECO:0000269|PubMed:23161544, ECO:0000269|PubMed:26359402}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in leaves, rhizomes and stems.
CC {ECO:0000269|PubMed:26359402}.
CC -!- INDUCTION: Transiently induced after wounding.
CC {ECO:0000269|PubMed:26359402}.
CC -!- BIOTECHNOLOGY: Combinatorially expression of Sinopodophyllum hexandrum
CC (mayapple) genes of the podophyllotoxin pathway (e.g. DIR, PLR, SDH,
CC CYP719A23, OMT3, CYP71CU1, OMT1, 2-ODD, CYP71BE54 and CYP82D61) in
CC Nicotiana benthamiana (tobacco) results in the production of the
CC chemotherapeutic compound etoposide. {ECO:0000305|PubMed:26359402}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KC110997; AGC29953.1; -; mRNA.
DR AlphaFoldDB; L7T8H2; -.
DR SMR; L7T8H2; -.
DR KEGG; ag:AGC29953; -.
DR BioCyc; MetaCyc:MON-19147; -.
DR BRENDA; 1.14.19.72; 4928.
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; IDA:UniProtKB.
DR GO; GO:0019438; P:aromatic compound biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009699; P:phenylpropanoid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEP:UniProtKB.
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_0000451901"
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"
SQ SEQUENCE 489 AA; 54215 MW; 47D3093B6848952B CRC64;
MEMEMSVLAM SSTLILALAM ALIFLFKAKS SSAIKWPPGP KTLPIIGNLH QLGGDELHIV
LAKLARVHGA IMTIWMAKKP VIVVSDVNSV WEVLVSKSSD YAARDAAEIS KIVSASSHSI
NTSDSGPYWQ TLRRGLTHGP LGPLNISAQI PIQQRDMQRV IREMQQDAAA NGGIIKPLDH
LKRSSTRLVS RLIFGDTFDN DPYNDSMHEV VQDLNRFGGI ALLEQAFSFA KHLPSYKRGV
KEFHIHKRKI DDLVRPVVAS ANPPSNSYLG FLQSQNYSEE IIIACIFELY LLAMDSSAST
ATWALAFMIR DQQVQEKLYQ DIKRVIGDGV DLVKAEDLSK MHYLQAVVKE TMRMKPIAPL
AIPHKTAIDT TVMGTKVPKG TCVMVNLYAL HHDESVWAKP YTFMPERFLQ GEDGKSVTEQ
AFLPFGAGMR ICGGMEVGKL QFSLALANLV NAFKWTSAAE GKLPDMSDEL QFITVMKTPL
EARIIPRNP
