ID   C71BE_SINHE             Reviewed;         507 AA.
AC   A0A0N9HT29;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2016, sequence version 1.
DT   03-AUG-2022, entry version 17.
DE   RecName: Full=Desmethyl-deoxy-podophyllotoxin synthase {ECO:0000303|PubMed:26359402};
DE            EC=1.14.14.- {ECO:0000269|PubMed:26359402};
DE   AltName: Full=Cytochrome P450 family 71 subfamily BE polypeptide 54 {ECO:0000303|PubMed:26359402};
GN   Name=CYP71BE54 {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   TISSUE SPECIFICITY, 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:26359402). Catalyzes the conversion of deoxypodophyllotoxin to
CC       desmethyl-deoxypodophyllotoxin (PubMed:26359402).
CC       {ECO:0000269|PubMed:26359402}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(-)-deoxypodophyllotoxin + O2 + reduced [NADPH--hemoprotein
CC         reductase] = (-)-4'-desmethyl-deoxypodophyllotoxin + formaldehyde +
CC         H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC         Xref=Rhea:RHEA:65572, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC         ChEBI:CHEBI:1729, ChEBI:CHEBI:4429, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16842,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000269|PubMed:26359402};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65573;
CC         Evidence={ECO:0000269|PubMed:26359402};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q96242};
CC   -!- PATHWAY: Aromatic compound metabolism; phenylpropanoid biosynthesis.
CC       {ECO:0000269|PubMed:26359402}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Rhizome-specific expression.
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; KT390179; ALG05141.1; -; mRNA.
DR   AlphaFoldDB; A0A0N9HT29; -.
DR   SMR; A0A0N9HT29; -.
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:UniProtKB-KW.
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   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..507
FT                   /note="Desmethyl-deoxy-podophyllotoxin synthase"
FT                   /id="PRO_5006035457"
FT   TRANSMEM        1..21
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         440
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   507 AA;  57408 MW;  1B37791A87766AAA CRC64;
     MEFLSFPLSS ALLIILLFML VKKAIQNKNS KLPPGPRKLP VIGSLHHLIG DGLPHHALRN
     LAKKHGPLMH LQLGENSTLV VSSSKMARAI MSTHDLMFAN RTVQFATDIL LYGGKGIGLA
     PYGDYWRQIR KICVLELLSA KRVQSFQTVR EEEISNLIRS ISAESSKVNF SEMITSLTND
     IIARAAFGEK CKDKHAFLSL IEEGIQLAGG FDIAGLFPSL KLLHVITGKK RQLERVHNEL
     DRILVDIIKE NKEKRRASKL NEDKYEENLV DVLVRVQENT QLEVPLANDN LKAVILDIFV
     AGSETSSTTI EWAMSEMLKN PKVMKKAQAE VRRVFSGNKK INETEIQELS YLKLVLKETL
     RLHAPAPLLI PRECRESCEI DGYEIPKKTM VMVNAWAIGR DPENWSNGDR FEPERFDGIS
     VDYKGTNFEY IPFGAGRRIC PGMLFGMANV EVPLARLLYH FDWELPNGIK PEELDMDETF
     GTTVRRKNHL YLIPTVVHEL ERSTTKE