CLDS9_SALSC
ID CLDS9_SALSC Reviewed; 784 AA.
AC G8GJ96; K4HZA9;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Copal-8-ol diphosphate hydratase TPSSA9, chloroplastic {ECO:0000305};
DE EC=4.2.1.133 {ECO:0000269|PubMed:22834731, ECO:0000269|PubMed:23113661};
DE AltName: Full=13-labden-8,15-diol pyrophosphate synthase TPSSA9 {ECO:0000303|PubMed:23113661};
DE Short=SsLPS {ECO:0000303|PubMed:23113661};
DE AltName: Full=Diterpene synthase Sa9 {ECO:0000303|PubMed:23113661};
DE Short=SsTpsSa9 {ECO:0000303|PubMed:23113661};
DE AltName: Full=Labd-13-en-8-ol diphosphate synthase {ECO:0000303|PubMed:22834731};
DE Short=SsLPPS {ECO:0000303|PubMed:22834731};
DE Flags: Precursor;
GN Name=LPS {ECO:0000303|PubMed:23113661};
GN Synonyms=LPPS {ECO:0000303|PubMed:22834731},
GN TPSSA9 {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.
RC TISSUE=Sepal;
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 produces 8-hydroxycopalyl
CC diphosphate from geranylgeranyl diphosphate (GGPP) (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=(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:22834731, ECO:0000269|PubMed:23113661};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32704;
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-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 -!- 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; JQ478434; AFU61897.1; -; mRNA.
DR EMBL; JN133924; AET21248.1; -; mRNA.
DR AlphaFoldDB; G8GJ96; -.
DR SMR; G8GJ96; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0009507; C:chloroplast; IDA: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 ?..784
FT /note="Copal-8-ol diphosphate hydratase TPSSA9,
FT chloroplastic"
FT /id="PRO_0000448858"
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 238
FT /note="Q -> K (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="L -> F (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="Q -> H (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="W -> L (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
FT CONFLICT 615
FT /note="I -> IS (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="S -> F (in Ref. 1; AFU61897)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 784 AA; 89657 MW; 33CE5C1C015B8B83 CRC64;
MTSVNLSRAP AAIIRRRLQL QPEFHAECSW LKSSSKHAPF TLSCQIRPKQ LSQIAELRVT
SLDASQASEK DISLVQTPHK VEVNEKIEES IEYVQNLLMT SGDGRISVSP YDTAVIALIK
DLKGRDAPQF PSCLEWIAHH QLADGSWGDE FFCIYDRILN TLACVVALKS WNLQSDIIEK
GVTYIKENVH KLKGANVEHR TAGFELVVPT FMQMATDLGI QGLPYDHPLI 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 QHQLEWIQMQ
EWYDRCSLSE FGISKRELLR SYFLAAATIF EPERTQERLL WAKTRILSKM ITSFVNISGT
TLSLDYNFNG LDEIISANED QGLAGTLLAT FHQLLDGFDI YTLHQLKHVW SQWFMKVQQG
EGSGGEDAVL LANTLNICAG LNEDVLSNNE YTALSTLTNK ICNRLAQIQD NKILQVVDGS
IKDKELEQDM QALVKLVLQE NGGAVDRNIR HTFLSVSKTF YYDAYHDDET TDLHIFKVLF
RPVV