C76K6_SALPM
ID C76K6_SALPM Reviewed; 500 AA.
AC A0A0S1TPC7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 17-FEB-2016, 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:0000269|PubMed:26976595};
DE AltName: Full=Cytochrome P450 76AK6 {ECO:0000303|PubMed:26572682};
DE Short=SpCYP76AK6 {ECO:0000303|PubMed:26572682};
DE AltName: Full=Miltiradien-20-al synthase {ECO:0000305};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A1D8QMD1};
DE AltName: Full=Pisiferic acid synthase {ECO:0000305};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A1D8QMG4};
GN Name=CYP76AK6 {ECO:0000303|PubMed:26572682};
OS Salvia pomifera (Apple 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=396869;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Trichome gland;
RX PubMed=26572682; DOI=10.1186/s12864-015-2147-3;
RA Trikka F.A., Nikolaidis A., Ignea C., Tsaballa A., Tziveleka L.A.,
RA Ioannou E., Roussis V., Stea E.A., Bozic D., Argiriou A., Kanellis A.K.,
RA Kampranis S.C., Makris A.M.;
RT "Combined metabolome and transcriptome profiling provides new insights into
RT diterpene biosynthesis in S. pomifera glandular trichomes.";
RL BMC Genomics 16:935-935(2015).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26976595; DOI=10.1073/pnas.1523787113;
RA Ignea C., Athanasakoglou A., Ioannou E., Georgantea P., Trikka F.A.,
RA Loupassaki S., Roussis V., Makris A.M., Kampranis S.C.;
RT "Carnosic acid biosynthesis elucidated by a synthetic biology platform.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:3681-3686(2016).
RN [3]
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
CC (PubMed:26976595). Catalyzes the oxidation of 11-hydroxyferruginol to
CC produce carnosate (PubMed:26976595). Mediates the conversion of
CC miltiradien into miltiradien-20-al (By similarity). Also involved in
CC the production of pisiferic acid and derivative products from
CC ferruginol (By similarity). {ECO:0000250|UniProtKB:A0A1D8QMD1,
CC ECO:0000250|UniProtKB:A0A1D8QMG4, ECO:0000269|PubMed:26976595}.
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:0000269|PubMed:26976595};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55433;
CC Evidence={ECO:0000269|PubMed:26976595};
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:0000250|UniProtKB:A0A1D8QMD1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66801;
CC Evidence={ECO:0000250|UniProtKB:A0A1D8QMD1};
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 leaf glandular trichomes.
CC {ECO:0000269|PubMed:26572682}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KT157045; ALM25797.1; -; mRNA.
DR AlphaFoldDB; A0A0S1TPC7; -.
DR SMR; A0A0S1TPC7; -.
DR KEGG; ag:ALM25797; -.
DR BRENDA; 1.14.14.61; 15442.
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; IDA:UniProtKB.
DR GO; GO:0016102; P:diterpenoid 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..500
FT /note="Carnosic acid synthase"
FT /id="PRO_5006591041"
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; 56161 MW; 95D5B5EED19126A8 CRC64;
MQVLILLSLA FLASCVVAYS RRRPGGRGAG DLPPGPPRLP IIGNMLQLGQ NPHKSLAHLA
KTYGPLMSLK LGNQFVVVVS SPEMAREVLQ RHGLVFSRPF TPIAVQILGH GEVSMNMLPA
TSPIWKKIRK IAREKLFSNQ ALHATRAVRR ERLRKLADYV GRCSGAMNVG EATFTTMSNL
MFATLFSVEI TQYADSDSDS GVNKKFREHV NAITRYMGVP NIADFFPIFA PFDPQGLRRK
LTYHLGSLLE LVQSLIEQRL RARNAATYRK KDDFLEMLLD LSEGDEYDLS VNEIKHLCVD
LIIAGSDTSA ATTEWAMVEL LLHPDKLAKL KAELKSVVGD KSIIEESDIS KLPYLQATVK
EVLRYHPAAP LLAPHLAEEE TQLNGYIIPK NTKIFINDWT ISRDPSIWKN PEMFEPERFL
NNDIDFCGQH FELIPFGSGR RICPGLPLAS RMLHCMVATL CHNFDWELEK GTESKQLQRE
DVFGLALQKK IPLRAIPIKV
