C7A47_PANGI
ID C7A47_PANGI Reviewed; 486 AA.
AC H2DH16; H2DH15;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Dammarenediol 12-hydroxylase {ECO:0000305};
DE EC=1.14.14.120 {ECO:0000269|PubMed:22039120};
DE AltName: Full=Cytochrome P450 CYP716A47 {ECO:0000303|PubMed:22039120, ECO:0000303|PubMed:25981048, ECO:0000303|PubMed:29509695};
DE AltName: Full=Protopanaxadiol synthase {ECO:0000303|PubMed:22039120};
DE Short=PgPPDS1 {ECO:0000303|PubMed:22039120};
GN Name=CYP716A47 {ECO:0000303|PubMed:22039120, ECO:0000303|PubMed:25981048,
GN ECO:0000303|PubMed:29509695, ECO:0000303|PubMed:30577538};
GN Synonyms=PPDS {ECO:0000303|PubMed:22039120, ECO:0000303|PubMed:29509695,
GN ECO:0000303|PubMed:30577538};
OS Panax ginseng (Korean ginseng).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Apiales; Araliaceae; Panax.
OX NCBI_TaxID=4054;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=22039120; DOI=10.1093/pcp/pcr150;
RA Han J.Y., Kim H.J., Kwon Y.S., Choi Y.E.;
RT "The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol
RT from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng.";
RL Plant Cell Physiol. 52:2062-2073(2011).
RN [2]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22875608; DOI=10.1093/pcp/pcs106;
RA Han J.Y., Hwang H.S., Choi S.W., Kim H.J., Choi Y.E.;
RT "Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol
RT from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng.";
RL Plant Cell Physiol. 53:1535-1545(2012).
RN [3]
RP TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=24603359; DOI=10.1038/cr.2014.28;
RA Yan X., Fan Y., Wei W., Wang P., Liu Q., Wei Y., Zhang L., Zhao G., Yue J.,
RA Zhou Z.;
RT "Production of bioactive ginsenoside compound K in metabolically engineered
RT yeast.";
RL Cell Res. 24:770-773(2014).
RN [4]
RP INDUCTION BY TWEEN 80.
RX PubMed=24889095; DOI=10.1002/bab.1256;
RA Liang Y., Wu J., Li Y., Li J., Ouyang Y., He Z., Zhao S.;
RT "Enhancement of ginsenoside biosynthesis and secretion by Tween 80 in Panax
RT ginseng hairy roots.";
RL Biotechnol. Appl. Biochem. 62:193-199(2015).
RN [5]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=25981048; DOI=10.1007/s00299-015-1806-9;
RA Chun J.-H., Adhikari P.B., Park S.-B., Han J.-Y., Choi Y.-E.;
RT "Production of the dammarene sapogenin (protopanaxadiol) in transgenic
RT tobacco plants and cultured cells by heterologous expression of PgDDS and
RT CYP716A47.";
RL Plant Cell Rep. 34:1551-1560(2015).
RN [6]
RP FUNCTION, AND INDUCTION BY ASPERGILLUS NIGER.
RX PubMed=27746309; DOI=10.1016/j.jbiotec.2016.10.011;
RA Li J., Liu S., Wang J., Li J., Liu D., Li J., Gao W.;
RT "Fungal elicitors enhance ginsenosides biosynthesis, expression of
RT functional genes as well as signal molecules accumulation in adventitious
RT roots of Panax ginseng C. A. Mey.";
RL J. Biotechnol. 239:106-114(2016).
RN [7]
RP REVIEW.
RX PubMed=29378087; DOI=10.1002/bab.1649;
RA Lu J., Li J., Wang S., Yao L., Liang W., Wang J., Gao W.;
RT "Advances in ginsenoside biosynthesis and metabolic regulation.";
RL Biotechnol. Appl. Biochem. 65:514-522(2018).
RN [8]
RP REVIEW, AND NOMENCLATURE.
RX PubMed=29509695; DOI=10.3390/molecules23030589;
RA Yang J.-L., Hu Z.-F., Zhang T.-T., Gu A.-D., Gong T., Zhu P.;
RT "Progress on the studies of the key enzymes of ginsenoside biosynthesis.";
RL Molecules 23:0-0(2018).
RN [9]
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND INDUCTION BY ABIOTIC FACTORS.
RX PubMed=30577538; DOI=10.3390/molecules24010014;
RA Zhang T., Han M., Yang L., Han Z., Cheng L., Sun Z., Yang L.;
RT "The effects of environmental factors on ginsenoside biosynthetic enzyme
RT gene expression and saponin abundance.";
RL Molecules 24:0-0(2018).
CC -!- FUNCTION: Component of the dammarane-type triterpene saponins (e.g.
CC ginsenosides or panaxosides) biosynthetic pathway (PubMed:22039120,
CC PubMed:25981048, PubMed:27746309, PubMed:29378087). Catalyzes the
CC hydroxylation of dammarenediol-II at the C-12 position to yield
CC protopanaxadiol in ginsenoside biosynthesis, a class of tetracyclic
CC triterpenoid saponins (PubMed:22039120, PubMed:25981048).
CC {ECO:0000269|PubMed:22039120, ECO:0000269|PubMed:25981048,
CC ECO:0000269|PubMed:27746309, ECO:0000303|PubMed:29378087}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dammarenediol-II + O2 + reduced [NADPH--hemoprotein reductase]
CC = (20S)-protopanaxadiol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38579, 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:62416,
CC ChEBI:CHEBI:75950; EC=1.14.14.120;
CC Evidence={ECO:0000269|PubMed:22039120};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38580;
CC Evidence={ECO:0000303|PubMed:29509695};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-20-O-(beta-D-glucosyl)-3-hydroxydammarene + O2 + reduced
CC [NADPH--hemoprotein reductase] = (20S)-ginsenoside C-K + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:59496,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:77146, ChEBI:CHEBI:142484;
CC Evidence={ECO:0000269|PubMed:24603359};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59497;
CC Evidence={ECO:0000269|PubMed:24603359};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Accumulates ubiquitously in all organs of plants
CC (PubMed:22875608). Mostly expressed in leaves and flowers, and, to a
CC lower extent, in roots and stems (PubMed:24603359, PubMed:30577538).
CC {ECO:0000269|PubMed:22875608, ECO:0000269|PubMed:24603359,
CC ECO:0000269|PubMed:30577538}.
CC -!- DEVELOPMENTAL STAGE: Rapid decrease in leaves from the leaf opened to
CC the green fruit stage (PubMed:30577538). Rapid and transient increase
CC in roots from the leaf opened to the green fruit stage
CC (PubMed:30577538). {ECO:0000269|PubMed:30577538}.
CC -!- INDUCTION: Up-regulated by methyl jasmonate (MeJA) (PubMed:22039120,
CC PubMed:22875608). Induced by A.niger mycelium-derived elicitor, thus
CC improving ginsenosides production in adventitious roots culture
CC (PubMed:27746309). Slightly induced by Tween 80 (PubMed:24889095).
CC Influenced in roots by soil water potential, and in leaves by
CC temperature, rain and relative humidity (PubMed:30577538).
CC {ECO:0000269|PubMed:22039120, ECO:0000269|PubMed:22875608,
CC ECO:0000269|PubMed:24889095, ECO:0000269|PubMed:27746309,
CC ECO:0000269|PubMed:30577538}.
CC -!- BIOTECHNOLOGY: Transgenic tobacco plants coexpressing PgDDS and
CC PgPPDS1/CYP716A47 accumulate dammarene sapogenin (protopanaxadiol,
CC PPD). {ECO:0000269|PubMed:25981048}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AEY75213.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; JN604536; AEY75212.1; -; mRNA.
DR EMBL; JN604537; AEY75213.1; ALT_INIT; mRNA.
DR AlphaFoldDB; H2DH16; -.
DR SMR; H2DH16; -.
DR KEGG; ag:AEY75212; -.
DR BioCyc; MetaCyc:MON-18259; -.
DR BRENDA; 1.14.13.183; 7895.
DR BRENDA; 1.14.14.120; 7895.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0102556; F:dammarenediol 12-hydroxylase 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:0002238; P:response to molecule of fungal origin; IEP:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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; Isoprene biosynthesis; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..486
FT /note="Dammarenediol 12-hydroxylase"
FT /id="PRO_0000425871"
FT TRANSMEM 8..28
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 486 AA; 55356 MW; 85C68EBB3589202B CRC64;
MAAAMVLFFS LSLLLLPLLL LFAYFSYTKR IPQKENDSKA PLPPGQTGWP LIGETLNYLS
CVKSGVSENF VKYRKEKYSP KVFRTSLLGE PMAILCGPEG NKFLYSTEKK LVQVWFPSSV
EKMFPRSHGE SNADNFSKVR GKMMFLLKVD GMKKYVGLMD RVMKQFLETD WNRQQQINVH
NTVKKYTVTM SCRVFMSIDD EEQVTRLGSS IQNIEAGLLA VPINIPGTAM NRAIKTVKLL
TREVEAVIKQ RKVDLLENKQ ASQPQDLLSH LLLTANQDGQ FLSESDIASH LIGLMQGGYT
TLNGTITFVL NYLAEFPDVY NQVLKEQVEI ANSKHPKELL NWEDLRKMKY SWNVAQEVLR
IIPPGVGTFR EAITDFTYAG YLIPKGWKMH LIPHDTHKNP TYFPSPEKFD PTRFEGNGPA
PYTFTPFGGG PRMCPGIEYA RLVILIFMHN VVTNFRWEKL IPNEKILTDP IPRFAHGLPI
HLHPHN