C76K7_ROSOF
ID C76K7_ROSOF Reviewed; 507 AA.
AC A0A1D8QMD2;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Carnosic acid synthase {ECO:0000305};
DE EC=1.14.14.61 {ECO:0000250|UniProtKB:A0A1D8QMG4};
DE AltName: Full=Cytochrome P450 76AK7 {ECO:0000303|PubMed:27703160};
DE Short=RoCYP76AK7 {ECO:0000303|PubMed:27703160};
DE AltName: Full=Miltiradien-20-al synthase {ECO:0000305|PubMed:27703160};
DE EC=1.14.14.- {ECO:0000269|PubMed:27703160};
DE AltName: Full=Pisiferic acid synthase {ECO:0000305|PubMed:27703160};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A1D8QMG4};
GN Name=CYP76AK7 {ECO:0000303|PubMed:27703160};
OS Rosmarinus officinalis (Rosemary) (Salvia rosmarinus).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Salviinae;
OC Salvia; Salvia subgen. Rosmarinus.
OX NCBI_TaxID=39367;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=27703160; DOI=10.1038/ncomms12942;
RA Scheler U., Brandt W., Porzel A., Rothe K., Manzano D., Bozic D.,
RA Papaefthimiou D., Balcke G.U., Henning A., Lohse S., Marillonnet S.,
RA Kanellis A.K., Ferrer A., Tissier A.;
RT "Elucidation of the biosynthesis of carnosic acid and its reconstitution in
RT yeast.";
RL Nat. Commun. 7:12942-12942(2016).
RN [2]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
CC -!- FUNCTION: Monooxygenase involved in the biosynthesis of carnosate, a
CC potent antioxidant labdane-related diterpene natural product (By
CC similarity). Catalyzes the oxidation of 11-hydroxyferruginol to produce
CC carnosate (By similarity). Mediates the conversion of miltiradien into
CC miltiradien-20-al (PubMed:27703160). Also involved in the production of
CC pisiferic acid and derivative products from ferruginol (By similarity).
CC {ECO:0000250|UniProtKB:A0A1D8QMG4, ECO:0000269|PubMed:27703160}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-hydroxyferruginol + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = carnosate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:55432, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138942, ChEBI:CHEBI:138943; EC=1.14.14.61;
CC Evidence={ECO:0000250|UniProtKB:A0A1D8QMG4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55433;
CC Evidence={ECO:0000250|UniProtKB:A0A1D8QMG4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=miltiradiene + 2 O2 + 2 reduced [NADPH--hemoprotein reductase]
CC = 2 H(+) + 3 H2O + miltiradien-20-al + 2 oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:66800, 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:65037,
CC ChEBI:CHEBI:167488; Evidence={ECO:0000269|PubMed:27703160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66801;
CC Evidence={ECO:0000269|PubMed:27703160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ferruginol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 4 H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase] +
CC pisiferate; Xref=Rhea:RHEA:66804, 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:78274,
CC ChEBI:CHEBI:167487; Evidence={ECO:0000250|UniProtKB:A0A1D8QMG4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66805;
CC Evidence={ECO:0000250|UniProtKB:A0A1D8QMG4};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q94IP1};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in glandular trichomes of young leaves.
CC {ECO:0000269|PubMed:27703160}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KX431219; AOW42545.1; -; mRNA.
DR AlphaFoldDB; A0A1D8QMD2; -.
DR SMR; A0A1D8QMD2; -.
DR UniPathway; UPA00213; -.
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:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:UniProt.
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; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..507
FT /note="Carnosic acid synthase"
FT /id="PRO_0000452737"
FT TRANSMEM 6..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 450
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:Q94IP1"
SQ SEQUENCE 507 AA; 57245 MW; 94AD66182FBA7ACE CRC64;
MDAFVVFSLA FLAAWFIVVF PRWSDSRRRR GPGGELPPGP PPLPIVGNIL QLRGDPHKSF
AQLAKTYGPL MSLRLGTQFA VVVSSPEMAT EILQKHGHAF SNRSIPDAIN IHGHNEVSWN
TMPADSTGWK RIRRVGREKL FSHQALQQTE GQRQERLRKL ADHVRGFSEQ GRVMNVGEAT
FTTMTDLVFS TLFSIDLTDY GATDSIANKE FKEHVNAFTR YIGVPNISDF FPIFAPLDPQ
GIRRKIGHHL GSLLAFVQSM IEERLRERKA STYQKKNDFL DTLLDISEEG NGYDDLSIKE
IRHFCVDIIV AGSDTSAATT EWAMVELLLH PDKLAKLKAE LKSFLGEKSL VEGSDISKLP
YLQATIKEVF RFHPAAPLLG PREAVEETQI NGYTIPKNAK IMVNFWAMTR DPSIWKNPES
FEPERFLGKD IDYEGQHFEL IPFGSGRRIC PGMPLASRML HCMVATLCHN FDWELEGGAE
SKQRQREDVF GLALQKKFPL RAKPIKV
