C7254_GLYUR
ID C7254_GLYUR Reviewed; 523 AA.
AC H1A988; A0A7G5VWJ8;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=11-oxo-beta-amyrin 30-oxidase {ECO:0000303|PubMed:22128119};
DE EC=1.14.14.115 {ECO:0000269|PubMed:22128119};
DE AltName: Full=Cytochrome P450 72A154 {ECO:0000303|PubMed:22128119};
GN Name=CYP72A154 {ECO:0000303|PubMed:22128119};
OS Glycyrrhiza uralensis (Chinese licorice) (Glycyrrhiza shiheziensis).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Fabales; Fabaceae; Papilionoideae; 50 kb inversion clade;
OC NPAAA clade; Hologalegina; IRL clade; Galegeae; Glycyrrhiza.
OX NCBI_TaxID=74613;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=22128119; DOI=10.1105/tpc.110.082685;
RA Seki H., Sawai S., Ohyama K., Mizutani M., Ohnishi T., Sudo H.,
RA Fukushima E.O., Akashi T., Aoki T., Saito K., Muranaka T.;
RT "Triterpene functional genomics in licorice for identification of CYP72A154
RT involved in the biosynthesis of glycyrrhizin.";
RL Plant Cell 23:4112-4123(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bi Q., Shen H.;
RL Submitted (OCT-2019) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, BIOTECHNOLOGY, AND REVIEW.
RX PubMed=31138208; DOI=10.1186/s12934-019-1138-5;
RA Wang C., Su X., Sun M., Zhang M., Wu J., Xing J., Wang Y., Xue J., Liu X.,
RA Sun W., Chen S.;
RT "Efficient production of glycyrrhetinic acid in metabolically engineered
RT Saccharomyces cerevisiae via an integrated strategy.";
RL Microb. Cell Fact. 18:95-95(2019).
CC -!- FUNCTION: Involved in the biosynthesis of Glycyrrhetinic acid (GA), a
CC natural product which exhibits anti-inflammatory activity
CC (PubMed:31138208). Involved in the biosynthesis of the triterpenoid
CC saponin glycyrrhizin (PubMed:22128119). Catalyzes three sequential
CC oxidation steps at C-30 of 11-oxo-beta-amyrin (PubMed:22128119). Also
CC able to catalyze C-30 monohydroxylation of beta-amyrin to produce 30-
CC hydroxy-beta-amyrin (PubMed:22128119). May be also responsible for the
CC oxidation at positions C-22 and C-29 in addition to C-30
CC (PubMed:22128119). {ECO:0000269|PubMed:22128119,
CC ECO:0000269|PubMed:31138208}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-oxo-beta-amyrin + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = glycyrrhetinate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:35499, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17573, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:63184; EC=1.14.14.115;
CC Evidence={ECO:0000269|PubMed:22128119};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-oxo-beta-amyrin + O2 + reduced [NADPH--hemoprotein
CC reductase] = 30-hydroxy-11-oxo-beta-amyrin + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:35503, Rhea:RHEA-
CC 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:63184, ChEBI:CHEBI:71576;
CC Evidence={ECO:0000269|PubMed:22128119};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=30-hydroxy-11-oxo-beta-amyrin + O2 + reduced [NADPH--
CC hemoprotein reductase] = glycyrrhetaldehyde + H(+) + 2 H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:35507, Rhea:RHEA-
CC 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:71576, ChEBI:CHEBI:71577;
CC Evidence={ECO:0000269|PubMed:22128119};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycyrrhetaldehyde + O2 + reduced [NADPH--hemoprotein
CC reductase] = glycyrrhetinate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:35511, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17573, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:71577;
CC Evidence={ECO:0000269|PubMed:22128119};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in roots, stolons and stems. Not detected
CC in leaves. {ECO:0000269|PubMed:22128119}.
CC -!- BIOTECHNOLOGY: Saccharomyces cerevisiae expressing Glycyrrhiza
CC uralensis CYP88D6 and CYP72A154, combined with the expression of
CC Arabidopsis thaliana beta-amyrin synthase (beta-AS) and NADPH-
CC cytochrome P450 reductase, accumulates glycyrrhetinic acid (GA) and, to
CC lower levels, beta-amyrin; these GA production was increased in the
CC presence of G.uralensis cytochrome b5 (GuCYB5).
CC {ECO:0000269|PubMed:31138208}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AB558153; BAL45207.1; -; mRNA.
DR EMBL; MN567153; QMX78160.1; -; mRNA.
DR AlphaFoldDB; H1A988; -.
DR SMR; H1A988; -.
DR KEGG; ag:BAL45207; -.
DR BioCyc; MetaCyc:MON-17470; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0102375; F:11-oxo-beta-amyrin 30-oxidase 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:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; IDA:UniProtKB.
DR GO; GO:1902382; P:11-oxo-beta-amyrin catabolic process; IDA:UniProtKB.
DR GO; GO:1902386; P:glycyrrhetinate 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..523
FT /note="11-oxo-beta-amyrin 30-oxidase"
FT /id="PRO_0000424183"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 471
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"
FT CONFLICT 25
FT /note="V -> A (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="V -> I (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
FT CONFLICT 267
FT /note="E -> D (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="R -> K (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="V -> F (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="E -> D (in Ref. 2; QMX78160)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 59020 MW; 4282412B8A123A8C CRC64;
MDASSTPGAI WVVLTVILAA IPIWVCHMVN TLWLRPKRLE RHLRAQGLHG DPYKLSLDNS
KQTYMLKLQQ EAQSKSIGLS KDDAAPRIFS LAHQTVHKYG KNSFAWEGTA PKVIITDPEQ
IKEVFNKIQD FPKPKLNPIA KYISIGLVQY EGDKWAKHRK IINPAFHLEK LKGMLPAFSH
SCHEMISKWK GLLSSDGTCE VDVWPFLQNL TCDVISRTAF GSSYAEGAKI FELLKRQGYA
LMTARYARIP LWWLLPSTTK RRMKEIERGI RDSLEGIIRK REKALKSGKS TDDDLLGILL
QSNHIENKGD ENSKSAGMTT QEVMEECKLF YLAGQETTAA LLAWTMVLLG KHPEWQARAR
QEVLQVFGNQ NPNFEGLGRL KIVTMILYEV LRLYPPGIYL TRALRKDLKL GNLLLPAGVQ
VSVPILLIHH DEGIWGNDAK EFNPERFAEG IAKATKGQVC YFPFGWGPRI CVGQNFALLE
AKIVLSLLLQ NFSFELSPTY AHVPTTVLTL QPKHGAPIIL HKL
