SCLS_SALSC
ID SCLS_SALSC Reviewed; 575 AA.
AC G8GJ94; K4HYB0;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Sclareol synthase, chloroplastic {ECO:0000303|PubMed:22834731, ECO:0000303|PubMed:23113661};
DE Short=ScSCS {ECO:0000303|PubMed:22834731};
DE Short=SsSS {ECO:0000303|PubMed:23113661};
DE EC=4.2.3.141 {ECO:0000269|PubMed:22834731, ECO:0000269|PubMed:23113661};
DE AltName: Full=Diterpene synthase 1132 {ECO:0000303|PubMed:23113661};
DE Short=SsTps1132 {ECO:0000303|PubMed:23113661};
DE Flags: Precursor;
GN Name=SCS {ECO:0000303|PubMed:23113661};
GN Synonyms=SS {ECO:0000303|PubMed:22834731},
GN Tps1132 {ECO:0000303|PubMed:23113661};
OS Salvia sclarea (Clary 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=38869;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, PATHWAY, AND BIOTECHNOLOGY.
RX PubMed=22834731; DOI=10.1186/1471-2229-12-119;
RA Caniard A., Zerbe P., Legrand S., Cohade A., Valot N., Magnard J.L.,
RA Bohlmann J., Legendre L.;
RT "Discovery and functional characterization of two diterpene synthases for
RT sclareol biosynthesis in Salvia sclarea (L.) and their relevance for
RT perfume manufacture.";
RL BMC Plant Biol. 12:119-119(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP BIOTECHNOLOGY.
RC TISSUE=Flower, Flower bud, and Leaf;
RX PubMed=23113661; DOI=10.1021/ja307404u;
RA Schalk M., Pastore L., Mirata M.A., Khim S., Schouwey M., Deguerry F.,
RA Pineda V., Rocci L., Daviet L.;
RT "Toward a biosynthetic route to sclareol and amber odorants.";
RL J. Am. Chem. Soc. 134:18900-18903(2012).
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: Involved in the biosynthesis of labdane-type diterpenoid
CC including sclareol, a diterpene-diol that is used as fragrance and
CC flavoring, and has anticancer effects (able to kill leukemic and colon
CC cancer cells by apoptosis) (Probable). Sclareol can also be used as
CC synthesis precursor of ambergris substitution fragance products such as
CC ambrox (Probable). Terpene synthase that catalyzes the conversion of 8-
CC hydroxy-copalyl diphosphate to sclareol (PubMed:23113661,
CC PubMed:22834731). {ECO:0000269|PubMed:22834731,
CC ECO:0000269|PubMed:23113661, ECO:0000305|PubMed:22834731,
CC ECO:0000305|PubMed:23113661, ECO:0000305|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-hydroxycopalyl diphosphate + H2O = diphosphate + sclareol;
CC Xref=Rhea:RHEA:34459, ChEBI:CHEBI:9053, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:64283; EC=4.2.3.141;
CC Evidence={ECO:0000269|PubMed:22834731, ECO:0000269|PubMed:23113661};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34460;
CC Evidence={ECO:0000269|PubMed:22834731, ECO:0000269|PubMed:23113661};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:22834731, ECO:0000269|PubMed:23113661,
CC ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Plastid, chloroplast
CC {ECO:0000269|PubMed:22834731}.
CC -!- DOMAIN: The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for
CC the catalytic activity, presumably through binding to Mg(2+).
CC {ECO:0000305}.
CC -!- BIOTECHNOLOGY: Escherichia coli expressing SsLPS and SsSCS from Salvia
CC sclarea and CrtE from Pantoea agglomerans can produce sclareol in high-
CC cell-density fermentation conditions, thus being an alternative,
CC sustainable, and cost-efficient route to sclareol and other diterpene
CC analogs. {ECO:0000269|PubMed:23113661}.
CC -!- BIOTECHNOLOGY: Yeast (S.cerevisiae) engineered to express S.cerevisiae
CC GGPPS and Salvia sclarea LPS and SCS is an efficient way to produce
CC sclareol in a scalable and potentially industrial way.
CC {ECO:0000269|PubMed:22834731}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; JQ478435; AFU61898.1; -; mRNA.
DR EMBL; JN133922; AET21246.1; -; mRNA.
DR AlphaFoldDB; G8GJ94; -.
DR SMR; G8GJ94; -.
DR KEGG; ag:AFU61898; -.
DR BRENDA; 4.2.3.141; 13177.
DR BRENDA; 4.2.3.B31; 13177.
DR UniPathway; UPA00213; -.
DR GO; GO:0009507; C:chloroplast; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0010333; F:terpene synthase activity; IEA:InterPro.
DR GO; GO:0016102; P:diterpenoid biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.600.10; -; 1.
DR Gene3D; 1.50.10.130; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR001906; Terpene_synth_N.
DR InterPro; IPR036965; Terpene_synth_N_sf.
DR InterPro; IPR005630; Terpene_synthase_metal-bd.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR Pfam; PF01397; Terpene_synth; 1.
DR Pfam; PF03936; Terpene_synth_C; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Chloroplast; Lyase; Magnesium; Metal-binding; Plastid; Transit peptide.
FT TRANSIT 1..51
FT /note="Chloroplast"
FT /evidence="ECO:0000255"
FT CHAIN 52..575
FT /note="Sclareol synthase, chloroplastic"
FT /evidence="ECO:0000255"
FT /id="PRO_0000448859"
FT MOTIF 329..333
FT /note="DDXXD motif"
FT /evidence="ECO:0000305"
FT BINDING 329
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 329
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 333
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 333
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 473
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 477
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 481
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT CONFLICT 23
FT /note="K -> N (in Ref. 1; AFU61898)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="I -> V (in Ref. 1; AFU61898)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 575 AA; 66681 MW; AA83712A0DF5475C CRC64;
MSLAFNVGVT PFSGQRVGSR KEKFPVQGFP VTTPNRSRLI VNCSLTTIDF MAKMKENFKR
EDDKFPTTTT LRSEDIPSNL CIIDTLQRLG VDQFFQYEIN TILDNTFRLW QEKHKVIYGN
VTTHAMAFRL LRVKGYEVSS EELAPYGNQE AVSQQTNDLP MIIELYRAAN ERIYEEERSL
EKILAWTTIF LNKQVQDNSI PDKKLHKLVE FYLRNYKGIT IRLGARRNLE LYDMTYYQAL
KSTNRFSNLC NEDFLVFAKQ DFDIHEAQNQ KGLQQLQRWY ADCRLDTLNF GRDVVIIANY
LASLIIGDHA FDYVRLAFAK TSVLVTIMDD FFDCHGSSQE CDKIIELVKE WKENPDAEYG
SEELEILFMA LYNTVNELAE RARVEQGRSV KEFLVKLWVE ILSAFKIELD TWSNGTQQSF
DEYISSSWLS NGSRLTGLLT MQFVGVKLSD EMLMSEECTD LARHVCMVGR LLNDVCSSER
EREENIAGKS YSILLATEKD GRKVSEDEAI AEINEMVEYH WRKVLQIVYK KESILPRRCK
DVFLEMAKGT FYAYGINDEL TSPQQSKEDM KSFVF
