C76H2_ROSOF
ID C76H2_ROSOF Reviewed; 493 AA.
AC A0A0C5Q4Y6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Ferruginol synthase 1 {ECO:0000303|PubMed:26020634};
DE Short=RoFS1 {ECO:0000303|PubMed:26020634};
DE EC=1.14.14.175 {ECO:0000269|PubMed:26020634};
DE AltName: Full=11-oxomiltiradiene synthase {ECO:0000305};
DE EC=1.14.14.- {ECO:0000250|UniProtKB:A0A0S1TP26};
DE AltName: Full=Cytochrome P450 76AH22 {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=CYP76AH22 {ECO:0000303|PubMed:27703160};
GN Synonyms=FS1 {ECO:0000303|PubMed:26020634},
GN HFS {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.
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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-301; SER-303 AND
RP PHE-478.
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}.
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DR EMBL; KP091843; AJQ30187.1; -; mRNA.
DR AlphaFoldDB; A0A0C5Q4Y6; -.
DR SMR; A0A0C5Q4Y6; -.
DR KEGG; ag:AJQ30187; -.
DR BRENDA; 1.14.14.175; 13767.
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..493
FT /note="Ferruginol synthase 1"
FT /id="PRO_0000452580"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 437
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"
FT MUTAGEN 301
FT /note="E->D: Loss of ferruginol monooxygenase activity;
FT when associated with N-303 and V-478."
FT /evidence="ECO:0000269|PubMed:27703160"
FT MUTAGEN 303
FT /note="S->N: Loss of ferruginol monooxygenase activity;
FT when associated with D-301 and V-478."
FT /evidence="ECO:0000269|PubMed:27703160"
FT MUTAGEN 478
FT /note="F->V: Loss of ferruginol monooxygenase activity;
FT when associated withD-301 and N-303."
FT /evidence="ECO:0000269|PubMed:27703160"
SQ SEQUENCE 493 AA; 56009 MW; 35E6BA1FFE92CC55 CRC64;
MDSFPLLAAL FFILAATWFI SFRRPRNLPP GPFPYPIVGN MLQLGTQPHE TFAKLSKKYG
PLMSIHLGSL YTVIVSSPEM AKEIMHKYGQ VFSGRTVAQA VHACGHDKIS MGFLPVGGEW
RDMRKICKEQ MFSHQSMEDS QWLRKQKLQQ LLEYAQKCSE RGRAIDIREA AFITTLNLMS
ATLFSMQATE FDSKVTMEFK EIIEGVASIV GVPNFADYFP ILRPFDPQGV KRRADVYFGR
LLAIIEGFLN ERVESRRTNP NAPKKDDFLE TLVDTLQTND NKLKTDHLTH LMLDLFVGGS
ETSTTEIEWI MWELLANPEK MAKMKAELKS VMGEEKVVDE SQMPRLPYLQ AVVKESMRLH
PPGPLLLPRK AESDQVVNGY LIPKGAQVLI NAWAIGRDHS IWKNPDSFEP ERFLDQKIDF
KGTDYELIPF GSGRRVCPGM PLANRILHTV TATLVHNFDW KLERPEASDA HRGVLFGFAV
RRAVPLKIVP FKV
