ID   C71CU_SINHE             Reviewed;         493 AA.
AC   A0A0N9HTU1;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2016, sequence version 1.
DT   03-AUG-2022, entry version 19.
DE   RecName: Full=Desmethylyatein synthase {ECO:0000303|PubMed:26359402};
DE            EC=1.14.14.131 {ECO:0000269|PubMed:26359402};
DE   AltName: Full=Cytochrome P450 family 71 subfamily CU polypeptide 1 {ECO:0000303|PubMed:26359402};
GN   Name=CYP71CU1 {ECO:0000303|PubMed:26359402};
GN   Synonyms=Phex524 {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   INDUCTION 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:26359402). Catalyzes the conversion of bursehernin to
CC       demethylyatein (PubMed:26359402). {ECO:0000269|PubMed:26359402}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(-)-bursehernin + O2 + reduced [NADPH--hemoprotein reductase]
CC         = (-)-5'-demethylyatein + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:49028, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:90893,
CC         ChEBI:CHEBI:90894; EC=1.14.14.131;
CC         Evidence={ECO:0000269|PubMed:26359402};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49029;
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   -!- 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; KT390172; ALG05134.1; -; mRNA.
DR   AlphaFoldDB; A0A0N9HTU1; -.
DR   SMR; A0A0N9HTU1; -.
DR   KEGG; ag:ALG05134; -.
DR   BRENDA; 1.14.14.131; 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: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   GO; GO:0009611; P:response to wounding; IEP: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..493
FT                   /note="Desmethylyatein synthase"
FT                   /id="PRO_5006035493"
FT   TRANSMEM        1..21
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         434
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   493 AA;  56562 MW;  86756CDFB6313981 CRC64;
     METFQCLTLF LLFISTVFIL KRKFSHKPNL PPSPPKLPIL GNFHQLGTLV HRAVTVLAAK
     YGPLMLLHFG KTPVLIVSSQ ETAKEIMKTH DLALANRPLT TAARALLYDC TDISFAPYGE
     YWREMKKMAV LNLLSIKKIQ SFRSVREELA SDMIKEITRL SKTGAPVDVT NMLYHFSEDL
     LFRCTLGFKP KGQHKFQKLS RDFLDLVGAF CFNDFFPGMA WMDALTGLNR KLKKGSRELD
     DFVDELIEER IAMVKDGVEP NEFLDLLLHT HRDTTQEIKL TRDNVKAIIL DTFLGGIDLP
     ASVMEWAMAE LMRNPSKMKI AQEEVRKVVG NKNKVDEDDV YQMNFLKSAV KETLRLHPPA
     PLLFARESYT SINVENYIIP PYTSVMINIW HIQRDPKLWD KAEEFIPERF MNSGIDYKSH
     DYEFIPFGSG RRGCPGMSFG VAAVEFAVAN LLYWFDWKFV GDTTPETLDM TEDYCFALFK
     KKPLHFIPIS RSS