OLIS_CANSA
ID OLIS_CANSA Reviewed; 385 AA.
AC B1Q2B6;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=3,5,7-trioxododecanoyl-CoA synthase;
DE EC=2.3.1.206 {ECO:0000269|PubMed:19454282, ECO:0000269|PubMed:19581347, ECO:0000269|Ref.3};
DE AltName: Full=Olivetol synthase {ECO:0000303|PubMed:19454282};
DE EC=4.4.1.- {ECO:0000269|PubMed:19454282, ECO:0000269|Ref.3};
DE AltName: Full=Polyketide synthase-1 {ECO:0000303|PubMed:18323613};
DE AltName: Full=Tetraketide synthase {ECO:0000303|PubMed:22802619};
GN Name=OLS {ECO:0000303|PubMed:19454282};
GN Synonyms=CAN24 {ECO:0000303|PubMed:19581347},
GN PKS-1 {ECO:0000303|PubMed:18323613}, TKS {ECO:0000303|PubMed:22802619};
OS Cannabis sativa (Hemp) (Marijuana).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Rosales; Cannabaceae; Cannabis.
OX NCBI_TaxID=3483;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=19454282; DOI=10.1016/j.febslet.2009.05.024;
RA Taura F., Tanaka S., Taguchi C., Fukamizu T., Tanaka H., Shoyama Y.,
RA Morimoto S.;
RT "Characterization of olivetol synthase, a polyketide synthase putatively
RT involved in cannabinoid biosynthetic pathway.";
RL FEBS Lett. 583:2061-2066(2009).
RN [2]
RP FUNCTION, AND CRYSTALLIZATION.
RX PubMed=18323613; DOI=10.1107/s1744309108003795;
RA Taguchi C., Taura F., Tamada T., Shoyama Y., Shoyama Y., Tanaka H.,
RA Kuroki R., Morimoto S.;
RT "Crystallization and preliminary X-ray diffraction studies of polyketide
RT synthase-1 (PKS-1) from Cannabis sativa.";
RL Acta Crystallogr. F 64:217-220(2008).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX DOI=10.1016/j.plantsci.2003.09.027;
RA Raharjo T.J., Chang W.-T., Choi Y.H., Peltenburg-Looman A.M.G.,
RA Verpoorte R.;
RT "Olivetol as product of a polyketide synthase in Cannabis sativa L.";
RL Plant Sci. 166:381-385(2004).
RN [4]
RP REVIEW.
RX PubMed=17712812; DOI=10.1002/cbdv.200790145;
RA Taura F., Sirikantaramas S., Shoyama Y., Shoyama Y., Morimoto S.;
RT "Phytocannabinoids in Cannabis sativa: recent studies on biosynthetic
RT enzymes.";
RL Chem. Biodivers. 4:1649-1663(2007).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=18854334; DOI=10.1093/pcp/pcn150;
RA Flores-Sanchez I.J., Verpoorte R.;
RT "PKS activities and biosynthesis of cannabinoids and flavonoids in Cannabis
RT sativa L. plants.";
RL Plant Cell Physiol. 49:1767-1782(2008).
RN [6]
RP CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=19581347; DOI=10.1093/jxb/erp210;
RA Marks M.D., Tian L., Wenger J.P., Omburo S.N., Soto-Fuentes W., He J.,
RA Gang D.R., Weiblen G.D., Dixon R.A.;
RT "Identification of candidate genes affecting Delta9-tetrahydrocannabinol
RT biosynthesis in Cannabis sativa.";
RL J. Exp. Bot. 60:3715-3726(2009).
RN [7]
RP FUNCTION, AND NOMENCLATURE.
RC STRAIN=cv. Finola;
RX PubMed=22802619; DOI=10.1073/pnas.1200330109;
RA Gagne S.J., Stout J.M., Liu E., Boubakir Z., Clark S.M., Page J.E.;
RT "Identification of olivetolic acid cyclase from Cannabis sativa reveals a
RT unique catalytic route to plant polyketides.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12811-12816(2012).
RN [8]
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 2-385 AND 2-99.
RA Kearsey L., Karuppiah V., Leys D., Takano E., Scrutton N.S.;
RT "Structure of a PKS class III from Cannabis sativa.";
RL Submitted (JUN-2018) to the PDB data bank.
CC -!- FUNCTION: Involved in the biosynthesis of cannabinoids-related
CC terpenophenolic natural products, which have pharmacological activity
CC (PubMed:18323613, PubMed:19454282, PubMed:19581347, PubMed:22802619).
CC Polyketide synthase responsible for olivetol biosynthesis, from a
CC C(12)-polyketide, probably 3,5,7-trioxododecanoyl-CoA (PubMed:19454282,
CC Ref.3). Catalyzes the first step in the cannabinoids biosynthetic
CC pathway. The preferred substrate is hexanoyl-CoA, but accepts also CoA
CC esters with C4 to C8 aliphatic side chains (PubMed:19454282). When
CC using malonyl-CoA and hexanoyl-CoA as substrates, produces undetermined
CC compounds distinct form olivetol or olivetolic acid (PubMed:19581347)
CC that could be hexanoyl triacetic acid lactone (HTAL) (PubMed:18323613)
CC and pentyl diacetic acid lactone (PDAL) (PubMed:22802619). Produces
CC olivetolic acid when acting in concert with olivetolic acid cyclase
CC (OAC). {ECO:0000269|PubMed:18323613, ECO:0000269|PubMed:19454282,
CC ECO:0000269|PubMed:19581347, ECO:0000269|PubMed:22802619,
CC ECO:0000269|Ref.3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H(+) + hexanoyl-CoA + 3 malonyl-CoA = 3,5,7-
CC trioxododecanoyl-CoA + 3 CO2 + 3 CoA; Xref=Rhea:RHEA:34119,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:62620, ChEBI:CHEBI:66957;
CC EC=2.3.1.206; Evidence={ECO:0000269|PubMed:19454282,
CC ECO:0000269|PubMed:19581347, ECO:0000269|Ref.3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34120;
CC Evidence={ECO:0000269|PubMed:19454282, ECO:0000269|PubMed:19581347,
CC ECO:0000269|Ref.3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,5,7-trioxododecanoyl-CoA = CO2 + CoA + olivetol;
CC Xref=Rhea:RHEA:20261, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:66957, ChEBI:CHEBI:66960;
CC Evidence={ECO:0000269|PubMed:19454282, ECO:0000269|Ref.3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20262;
CC Evidence={ECO:0000269|PubMed:19454282, ECO:0000269|Ref.3};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=60.8 uM for hexanoyl-CoA {ECO:0000269|PubMed:19454282};
CC KM=88.9 uM for butyryl-CoA {ECO:0000269|PubMed:19454282};
CC KM=99.1 uM for isovaleryl-CoA {ECO:0000269|PubMed:19454282};
CC KM=81.7 uM for octanoyl-CoA {ECO:0000269|PubMed:19454282};
CC Note=kcat is 2.96 min(-1) with hexanoyl-CoA as substrate
CC (PubMed:19454282). kcat is 0.719 min(-1) with butyryl-CoA as
CC substrate (PubMed:19454282). kcat is 0.585 min(-1) with isovaleryl-
CC CoA as substrate (PubMed:19454282). kcat is 0.525 min(-1) with
CC octanoyl-CoA as substrate (PubMed:19454282).
CC {ECO:0000269|PubMed:19454282};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- TISSUE SPECIFICITY: Expressed in bracts, flowers and young leaves. Not
CC detected in mature leaves, roots and stems. Expressed in glandular
CC trichomes. {ECO:0000269|PubMed:18854334, ECO:0000269|PubMed:19454282,
CC ECO:0000269|Ref.3}.
CC -!- POLYMORPHISM: Several isoforms exist due to polymorphism.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; AB164375; BAG14339.1; -; mRNA.
DR PDB; 6GW3; X-ray; 1.39 A; A/B/C/D=2-385, D=2-99.
DR PDB; 7W6G; X-ray; 2.10 A; A/B/C/D=1-385.
DR PDBsum; 6GW3; -.
DR PDBsum; 7W6G; -.
DR AlphaFoldDB; B1Q2B6; -.
DR SMR; B1Q2B6; -.
DR KEGG; ag:BAG14339; -.
DR BRENDA; 2.3.1.206; 1159.
DR SABIO-RK; B1Q2B6; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:1901696; P:cannabinoid biosynthetic process; TAS:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR012328; Chalcone/stilbene_synt_C.
DR InterPro; IPR001099; Chalcone/stilbene_synt_N.
DR InterPro; IPR018088; Chalcone/stilbene_synthase_AS.
DR InterPro; IPR011141; Polyketide_synthase_type-III.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11877; PTHR11877; 1.
DR Pfam; PF02797; Chal_sti_synt_C; 1.
DR Pfam; PF00195; Chal_sti_synt_N; 1.
DR PIRSF; PIRSF000451; PKS_III; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR PROSITE; PS00441; CHALCONE_SYNTH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Lyase; Transferase.
FT CHAIN 1..385
FT /note="3,5,7-trioxododecanoyl-CoA synthase"
FT /id="PRO_0000421147"
FT ACT_SITE 157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10023"
FT STRAND 10..18
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 29..36
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 43..55
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 84..110
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 133..141
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 159..173
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 199..207
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 211..220
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 230..240
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 247..253
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 265..281
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 291..296
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:6GW3"
FT TURN 315..318
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 319..328
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:6GW3"
FT HELIX 335..349
FT /evidence="ECO:0007829|PDB:6GW3"
FT TURN 355..358
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 360..368
FT /evidence="ECO:0007829|PDB:6GW3"
FT TURN 369..371
FT /evidence="ECO:0007829|PDB:6GW3"
FT STRAND 372..380
FT /evidence="ECO:0007829|PDB:6GW3"
SQ SEQUENCE 385 AA; 42585 MW; B9AD431F65194C0B CRC64;
MNHLRAEGPA SVLAIGTANP ENILLQDEFP DYYFRVTKSE HMTQLKEKFR KICDKSMIRK
RNCFLNEEHL KQNPRLVEHE MQTLDARQDM LVVEVPKLGK DACAKAIKEW GQPKSKITHL
IFTSASTTDM PGADYHCAKL LGLSPSVKRV MMYQLGCYGG GTVLRIAKDI AENNKGARVL
AVCCDIMACL FRGPSESDLE LLVGQAIFGD GAAAVIVGAE PDESVGERPI FELVSTGQTI
LPNSEGTIGG HIREAGLIFD LHKDVPMLIS NNIEKCLIEA FTPIGISDWN SIFWITHPGG
KAILDKVEEK LHLKSDKFVD SRHVLSEHGN MSSSTVLFVM DELRKRSLEE GKSTTGDGFE
WGVLFGFGPG LTVERVVVRS VPIKY
