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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
 
 
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