C76K6_SALFT
ID C76K6_SALFT Reviewed; 500 AA.
AC A0A1D8QMD1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Carnosic acid synthase {ECO:0000305};
DE EC=1.14.14.61 {ECO:0000250|UniProtKB:A0A1D8QMG4};
DE AltName: Full=Cytochrome P450 76AK6 {ECO:0000303|PubMed:27703160};
DE Short=SfCYP76AK6 {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=CYP76AK6 {ECO:0000303|PubMed:27703160};
OS Salvia fruticosa (Greek sage).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Salviinae;
OC Salvia; Salvia incertae sedis.
OX NCBI_TaxID=268906;
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: Mostly expressed in young leaves, particularly in
CC glandular trichomes. {ECO:0000269|PubMed:27703160}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KX431218; AOW42544.1; -; mRNA.
DR AlphaFoldDB; A0A1D8QMD1; -.
DR SMR; A0A1D8QMD1; -.
DR KEGG; ag:AOW42544; -.
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..500
FT /note="Carnosic acid synthase"
FT /id="PRO_5009111420"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 443
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 500 AA; 56138 MW; DB45A6DA0CB13110 CRC64;
MQVLILLSLA FLASCVVAYS RRRPGGRGAG NLPPGPPRLP IIGNMLQLGQ NPHKSLAHLA
KTYGPLMSLK LGNQFVVVVS SPEMAREVLQ RHGLVFSTPC APIAVQILGH GEVSMNMLPA
TSPIWKKLRK IAREKLFSNQ ALHDTRAVRW ERLRKLADYV GRCSGAMNVG EATFTTMSNL
MFSTLFSVEI TQYADSDSDS GVNKKFREHV NAITRYIGVP NIADFFPIFA PFDPQGLRRK
LTYHFGSLLE LVQSLIEQRL RARNAATYRK KDDFLEMLLD LSEGDEYDLS VNEIKHLCVD
LIIAGSDTSA ATTEWAMVEL LLHPDKLAKL KAELKSVVGD KSIIEESDIS KLPYLQATVK
EVLRYHPAAP LLAPHLAEEE TQLNGYIIPK NTKIFINDWT ISRDPSIWKN PEMFEPERFL
DNDIDFCGQH FELIPFGSGR RICPGLPLAS RMLHCMVATL CHNFDWELEK GTESKQLQRE
DVFGLALQKK IPLRAIPIKV
