CLDS3_SALSC
ID CLDS3_SALSC Reviewed; 785 AA.
AC G8GJ95; J9PDV7;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Copal-8-ol diphosphate hydratase TPSSA3, chloroplastic {ECO:0000305};
DE Short=8-hydroxycopalyl diphosphate synthase {ECO:0000305};
DE EC=4.2.1.133 {ECO:0000269|PubMed:22959531, ECO:0000269|PubMed:23113661};
DE AltName: Full=13-labden-8,15-diol pyrophosphate synthase TPSSA3 {ECO:0000303|PubMed:23113661};
DE Short=SsLPS {ECO:0000303|PubMed:23113661};
DE AltName: Full=Diterpene synthase 1, chloroplastic {ECO:0000303|PubMed:22959531};
DE Short=SscTPS1 {ECO:0000303|PubMed:22959531};
DE AltName: Full=Diterpene synthase Sa3 {ECO:0000303|PubMed:23113661};
DE Short=SsTpsSa3 {ECO:0000303|PubMed:23113661};
DE Flags: Precursor;
GN Name=LPS {ECO:0000303|PubMed:23113661};
GN Synonyms=TPS1 {ECO:0000303|PubMed:22959531},
GN TPSSA3 {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, 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=cv. Trakystra; TISSUE=Leaf, Root, Stem, and Trichome gland;
RX PubMed=22959531; DOI=10.1016/j.phytochem.2012.07.019;
RA Guennewich N., Higashi Y., Feng X., Choi K.-B., Schmidt J., Kutchan T.M.;
RT "A diterpene synthase from the clary sage Salvia sclarea catalyzes the
RT cyclization of geranylgeranyl diphosphate to (8R)-hydroxy-copalyl
RT diphosphate.";
RL Phytochemistry 91:93-99(2013).
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 produces 8-hydroxycopalyl
CC diphosphate from geranylgeranyl diphosphate (GGPP) (PubMed:23113661,
CC PubMed:22959531). {ECO:0000269|PubMed:22959531,
CC ECO:0000269|PubMed:23113661, ECO:0000305|PubMed:22959531,
CC ECO:0000305|PubMed:23113661, ECO:0000305|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + H2O = 8-
CC hydroxycopalyl diphosphate; Xref=Rhea:RHEA:32703, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:58756, ChEBI:CHEBI:64283; EC=4.2.1.133;
CC Evidence={ECO:0000269|PubMed:22959531, ECO:0000269|PubMed:23113661};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32704;
CC Evidence={ECO:0000269|PubMed:22959531, ECO:0000269|PubMed:23113661};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q38802};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:22959531, ECO:0000269|PubMed:23113661,
CC ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Plastid, chloroplast
CC {ECO:0000250|UniProtKB:G8GJ96}.
CC -!- DOMAIN: The Asp-Xaa-Asp-Asp (DXDD) motif is important for the catalytic
CC activity, presumably through binding to Mg(2+). {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 -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; JN133923; AET21247.1; -; mRNA.
DR EMBL; HQ641451; ADW66454.1; -; mRNA.
DR AlphaFoldDB; G8GJ95; -.
DR SMR; G8GJ95; -.
DR BRENDA; 4.2.3.133; 13177.
DR UniPathway; UPA00213; -.
DR GO; GO:0009507; C:chloroplast; ISS:UniProtKB.
DR GO; GO:0102161; F:copal-8-ol diphosphate synthase activity; 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; 2.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Chloroplast; Lyase; Magnesium; Metal-binding; Plastid; Transit peptide.
FT TRANSIT 1..?
FT /note="Chloroplast"
FT /evidence="ECO:0000255"
FT CHAIN ?..785
FT /note="Copal-8-ol diphosphate hydratase TPSSA3,
FT chloroplastic"
FT /id="PRO_0000448857"
FT MOTIF 372..375
FT /note="DXDD motif"
FT /evidence="ECO:0000305"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q38802"
FT BINDING 372
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:C7BKP9"
FT BINDING 374
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:C7BKP9"
FT BINDING 459
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q38802"
FT CONFLICT 596
FT /note="N -> K (in Ref. 2; ADW66454)"
FT /evidence="ECO:0000305"
FT CONFLICT 667
FT /note="E -> D (in Ref. 2; ADW66454)"
FT /evidence="ECO:0000305"
FT CONFLICT 672..675
FT /note="LANT -> QANA (in Ref. 2; ADW66454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 785 AA; 89774 MW; 5B0BAD5B13ED9121 CRC64;
MTSVNLSRAP AAITRRRLQL QPEFHAECSW LKSSSKHAPL TLSCQIRPKQ LSQIAELRVT
SLDASQASEK DISLVQTPHK VEVNEKIEES IEYVQNLLMT SGDGRISVSP YDTAVIALIK
DLKGRDAPQF PSCLEWIAHH QLADGSWGDE FFCIYDRILN TLACVVALKS WNLHSDIIEK
GVTYIKENVH KLKGANVEHR TAGFELVVPT FMQMATDLGI QDLPYDHPLI KEIADTKQQR
LKEIPKDLVY QMPTNLLYSL EGLGDLEWER LLKLQSGNGS FLTSPSSTAA VLMHTKDEKC
LKYIENALKN CDGGAPHTYP VDIFSRLWAI DRLQRLGISR FFQHEIKYFL DHIESVWEET
GVFSGRYTKF SDIDDTSMGV RLLKMHGYDV DPNVLKHFKQ QDGKFSCYIG QSVESASPMY
NLYRAAQLRF PGEEVLEEAT KFAFNFLQEM LVKDRLQERW VISDHLFDEI KLGLKMPWYA
TLPRVEAAYY LDHYAGSGDV WIGKSFYRMP EISNDTYKEL AILDFNRCQT QHQLEWIHMQ
EWYDRCSLSE FGISKRELLR SYFLAAATIF EPERTQERLL WAKTRILSKM ITSFVNISGT
TLSLDYNFNG LDEIISSANE DQGLAGTLLA TFHQLLDGFD IYTLHQLKHV WSQWFMKVQQ
GEGSGGEDAV LLANTLNICA GLNEDVLSNN EYTALSTLTN KICNRLAQIQ DNKILQVVDG
SIKDKELEQD MQALVKLVLQ ENGGAVDRNI RHTFLSVSKT FYYDAYHDDE TTDLHIFKVL
FRPVV
