C76K8_ROSOF
ID C76K8_ROSOF Reviewed; 504 AA.
AC A0A1D8QMG4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Carnosic acid synthase {ECO:0000305};
DE EC=1.14.14.61 {ECO:0000269|PubMed:26976595};
DE AltName: Full=Cytochrome P450 76AK8 {ECO:0000303|PubMed:27703160};
DE Short=RoCYP76AK8 {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:0000269|PubMed:27703160};
GN Name=CYP76AK8 {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 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 products
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 (PubMed:27703160). Also involved in
CC the production of pisiferic acid and derivative products from
CC ferruginol (PubMed:27703160). {ECO:0000269|PubMed:26976595,
CC 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: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: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:0000269|PubMed:27703160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66805;
CC Evidence={ECO:0000269|PubMed:27703160};
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; KX431220; AOW42546.1; -; mRNA.
DR AlphaFoldDB; A0A1D8QMG4; -.
DR SMR; A0A1D8QMG4; -.
DR BioCyc; MetaCyc:MON-21173; -.
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..504
FT /note="Carnosic acid synthase"
FT /id="PRO_5009111366"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 447
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 504 AA; 56686 MW; D26365F7F15450C2 CRC64;
MQLFIILSLA FIAAWVVYSR WSEYSRGRQG GSGGLPPGPP RLPIIGNILQ LGRDPHKSLA
QLAKTYGPLM SLKLGNQFAV VVSSPEMARE ILQKQGLIFS KPFTPSAVRV LGHNDISMNM
LPASSDRWKK LRRVAREQLF SNPALQATQD IRQERLRQLT DYASRCCAQG RAMNVGEATF
TTMTNLMFAT LFSVELTQYG ATDTGSDKKF KEHVNALTRY MGVPNVADFF PFLAPLDPQG
MRRKLTYHLG SLLELVQSLI QQRLQARNDS TYQKKNDFLD TLLDLSEGNE YDLSIKEIKH
MFVDLIIAGS DTSAATTEWA MVELLLHPDK MAKLKAELKS VLGEKSIVEE SDISRLPYLL
ATVKEVLRYH PAAPLLAPHA AEEETQVSGY IIPKNTKMFI NVWSITRDPS IWKNPESFEP
ERFLDSEIDF GGQHFELIPF GSGRRICPGM PLASRMLQCM VATLCHNFDW ELEKGAESKQ
LQREDVFGLA LQKKIPLRAV PIKV
