C76H2_SALFT
ID C76H2_SALFT Reviewed; 492 AA.
AC A0A0C5QRZ2;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Ferruginol synthase {ECO:0000303|PubMed:26020634};
DE Short=SfFS {ECO:0000303|PubMed:26020634};
DE EC=1.14.14.175 {ECO:0000269|PubMed:26020634, ECO:0000269|PubMed:27703160};
DE AltName: Full=11-oxomiltiradiene synthase {ECO:0000305};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A0S1TP26};
DE AltName: Full=Cytochrome P450 76AH24 {ECO:0000303|PubMed:27703160};
DE AltName: Full=Ferruginol monooxygenase {ECO:0000305};
DE Short=11-hydroxyferruginol synthase {ECO:0000303|PubMed:27703160};
DE EC=1.14.14.60 {ECO:0000269|PubMed:27703160};
DE AltName: Full=Miltiradiene oxidase {ECO:0000305};
GN Name=CYP76AH24 {ECO:0000303|PubMed:27703160};
GN Synonyms=FS {ECO:0000303|PubMed:26020634},
GN HFS {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.
RC TISSUE=Trichome gland;
RX PubMed=26020634; DOI=10.1371/journal.pone.0124106;
RA Bozic D., Papaefthimiou D., Brueckner K., de Vos R.C., Tsoleridis C.A.,
RA Katsarou D., Papanikolaou A., Pateraki I., Chatzopoulou F.M.,
RA Dimitriadou E., Kostas S., Manzano D., Scheler U., Ferrer A., Tissier A.,
RA Makris A.M., Kampranis S.C., Kanellis A.K.;
RT "Towards elucidating carnosic acid biosynthesis in Lamiaceae: Functional
RT characterization of the three first steps of the pathway in Salvia
RT fruticosa and Rosmarinus officinalis.";
RL PLoS ONE 10:e0124106-e0124106(2015).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [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 labdane-related
CC diterpenes natural products (PubMed:26020634, PubMed:27703160).
CC Catalyzes the oxidation of abietatriene to produce ferruginol
CC (PubMed:26020634, PubMed:27703160). Catalyzes the oxidation of
CC ferruginol at C-12 to produce 11-hydroxyferruginol (PubMed:27703160).
CC Ferruginol and 11-hydroxyferruginol are intermediates in the
CC biosynthesis of carnosate, a potent antioxidant (PubMed:26020634,
CC PubMed:27703160). May also convert miltiradiene into 11-oxomiltiradiene
CC (By similarity). {ECO:0000250|UniProtKB:A0A0S1TP26,
CC ECO:0000269|PubMed:26020634, ECO:0000269|PubMed:27703160}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=abieta-8,11,13-triene + O2 + reduced [NADPH--hemoprotein
CC reductase] = ferruginol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:48080, 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:86062; EC=1.14.14.175;
CC Evidence={ECO:0000269|PubMed:26020634, ECO:0000269|PubMed:27703160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48081;
CC Evidence={ECO:0000269|PubMed:26020634, ECO:0000269|PubMed:27703160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ferruginol + O2 + reduced [NADPH--hemoprotein reductase] = 11-
CC hydroxyferruginol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55428, 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:138942; EC=1.14.14.60;
CC Evidence={ECO:0000269|PubMed:27703160};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55429;
CC Evidence={ECO:0000269|PubMed:27703160};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=miltiradiene + 2 O2 + 2 reduced [NADPH--hemoprotein reductase]
CC = 11-oxomiltiradiene + 2 H(+) + 3 H2O + 2 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:66796, 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:65037, ChEBI:CHEBI:167496;
CC Evidence={ECO:0000250|UniProtKB:A0A0S1TP26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66797;
CC Evidence={ECO:0000250|UniProtKB:A0A0S1TP26};
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:26020634}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KP091842; AJQ30186.1; -; mRNA.
DR AlphaFoldDB; A0A0C5QRZ2; -.
DR SMR; A0A0C5QRZ2; -.
DR KEGG; ag:AJQ30186; -.
DR BioCyc; MetaCyc:MON-19365; -.
DR BRENDA; 1.14.14.175; 12982.
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..492
FT /note="Ferruginol synthase"
FT /id="PRO_0000452579"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 436
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 492 AA; 55616 MW; 0B96E60C80C96169 CRC64;
MDPFPLVAAA LFIAATWFIT FKRRRNLPPG PFPYPIVGNM LQLGSQPHET FAKLSKKYGP
LMSIHLGSLY TVIISSPEMA KEIMHKYGQV FSGRTIAQAV HACDHDKISM GFLPVGAEWR
DMRKICKEQM FSHQSMEDSQ NLRKQKLQQL LEYAQKCSEE GRGIDIREAA FITTLNLMSA
TLFSMQATEF DSKVTMEFKE IIEGVASIVG VPNFADYFPI LRPFDPQGVK RRADVYFGRL
LGLIEGYLNE RIEFRKANPN APKKDDFLET LVDALDAKDY KLKTEHLTHL MLDLFVGGSE
TSTTEIEWIM WELLASPEKM AKVKAELKSV MGGEKVVDES MMPRLPYLQA VVKESMRLHP
PGPLLLPRKA ESDQVVNGYL IPKGAQVLIN AWAMGRDPSL WKNPDSFEPE RFLDQKIDFK
GTDYELIPFG SGRRVCPGMP LANRILHTVT ATLVHNFDWK LERPEASDAH KGVLFGFAVR
RAVPLKIVPI KA
