ID   CYC2_STRCO              Reviewed;         726 AA.
AC   Q9X839;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 127.
DE   RecName: Full=Germacradienol/geosmin synthase;
DE   Includes:
DE     RecName: Full=Germacradienol/germacrene D synthase;
DE              EC=4.2.3.22;
DE              EC=4.2.3.75;
DE     AltName: Full=Sesquiterpene cyclase;
DE     AltName: Full=Sesquiterpene synthase;
DE   Includes:
DE     RecName: Full=Geosmin synthase;
DE              EC=4.1.99.16;
GN   Name=cyc2; OrderedLocusNames=SCO6073; ORFNames=SC9B1.20;
OS   Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145).
OC   Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales;
OC   Streptomycetaceae; Streptomyces; Streptomyces albidoflavus group.
OX   NCBI_TaxID=100226;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-471 / A3(2) / M145;
RX   PubMed=12000953; DOI=10.1038/417141a;
RA   Bentley S.D., Chater K.F., Cerdeno-Tarraga A.-M., Challis G.L.,
RA   Thomson N.R., James K.D., Harris D.E., Quail M.A., Kieser H., Harper D.,
RA   Bateman A., Brown S., Chandra G., Chen C.W., Collins M., Cronin A.,
RA   Fraser A., Goble A., Hidalgo J., Hornsby T., Howarth S., Huang C.-H.,
RA   Kieser T., Larke L., Murphy L.D., Oliver K., O'Neil S., Rabbinowitsch E.,
RA   Rajandream M.A., Rutherford K.M., Rutter S., Seeger K., Saunders D.,
RA   Sharp S., Squares R., Squares S., Taylor K., Warren T., Wietzorrek A.,
RA   Woodward J.R., Barrell B.G., Parkhill J., Hopwood D.A.;
RT   "Complete genome sequence of the model actinomycete Streptomyces coelicolor
RT   A3(2).";
RL   Nature 417:141-147(2002).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-10, FUNCTION, CATALYTIC ACTIVITY, DOMAIN, KINETIC
RP   PARAMETERS, AND COFACTOR.
RC   STRAIN=ATCC BAA-471 / A3(2) / M145;
RX   PubMed=12556563; DOI=10.1073/pnas.0337625100;
RA   Cane D.E., Watt R.M.;
RT   "Expression and mechanistic analysis of a germacradienol synthase from
RT   Streptomyces coelicolor implicated in geosmin biosynthesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:1547-1551(2003).
RN   [3]
RP   DOMAIN, AND ROLE IN GEOSMIN BIOSYNTHESIS.
RC   STRAIN=ATCC BAA-471 / A3(2) / M145;
RX   PubMed=12563033; DOI=10.1073/pnas.0337542100;
RA   Gust B., Challis G.L., Fowler K., Kieser T., Chater K.F.;
RT   "PCR-targeted Streptomyces gene replacement identifies a protein domain
RT   needed for biosynthesis of the sesquiterpene soil odor geosmin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:1541-1546(2003).
RN   [4]
RP   FUNCTION IN GERMACRENE D PRODUCTION, AND REACTION STEREOCHEMISTRY.
RC   STRAIN=ATCC BAA-471 / A3(2) / M145;
RX   PubMed=14995166; DOI=10.1021/ja039929k;
RA   He X., Cane D.E.;
RT   "Mechanism and stereochemistry of the germacradienol/germacrene D synthase
RT   of Streptomyces coelicolor A3(2).";
RL   J. Am. Chem. Soc. 126:2678-2679(2004).
RN   [5]
RP   FUNCTION IN DIRECT GEOSMIN PRODUCTION, COFACTOR, AND REACTION MECHANISM.
RC   STRAIN=ATCC BAA-471 / A3(2) / M145;
RX   PubMed=16787064; DOI=10.1021/ja062669x;
RA   Jiang J., He X., Cane D.E.;
RT   "Geosmin biosynthesis. Streptomyces coelicolor germacradienol/germacrene D
RT   synthase converts farnesyl diphosphate to geosmin.";
RL   J. Am. Chem. Soc. 128:8128-8129(2006).
CC   -!- FUNCTION: Tow-domain protein where the N-terminal domain catalyzes the
CC       cyclization of farnesyl diphosphate (FPP) to a 85:15 mixture of the
CC       sesquiterpene alcohol germacradienol and the sesquiterpene hydrocarbon
CC       germacrene D. The C-terminal domain partially converts the
CC       germacradienol formed into geosmin, the characteristic odoriferous
CC       ('earthy aroma') constituent of Streptomyces species.
CC       {ECO:0000269|PubMed:12556563, ECO:0000269|PubMed:12563033,
CC       ECO:0000269|PubMed:14995166, ECO:0000269|PubMed:16787064}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-
CC         1(10),5-dien-11-ol + diphosphate; Xref=Rhea:RHEA:22436,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:33019, ChEBI:CHEBI:46734,
CC         ChEBI:CHEBI:175763; EC=4.2.3.22;
CC         Evidence={ECO:0000269|PubMed:12556563};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + H2O = (-)-geosmin
CC         + acetone; Xref=Rhea:RHEA:30371, ChEBI:CHEBI:15347,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:46702, ChEBI:CHEBI:46734;
CC         EC=4.1.99.16; Evidence={ECO:0000269|PubMed:12556563};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesyl diphosphate = (-)-germacrene D + diphosphate;
CC         Xref=Rhea:RHEA:12016, ChEBI:CHEBI:33019, ChEBI:CHEBI:49044,
CC         ChEBI:CHEBI:175763; EC=4.2.3.75;
CC         Evidence={ECO:0000269|PubMed:12556563};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:12556563, ECO:0000269|PubMed:16787064};
CC       Note=Magnesium. Fe(2+) or Cu(2+) ions are very less efficient as
CC       cofactors. {ECO:0000269|PubMed:12556563, ECO:0000269|PubMed:16787064};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=62 nM for FPP {ECO:0000269|PubMed:12556563};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; geosmin biosynthesis.
CC   -!- PATHWAY: Sesquiterpene biosynthesis; germacradienol biosynthesis;
CC       germacradienol from farnesyl diphosphate: step 1/1.
CC   -!- PATHWAY: Sesquiterpene biosynthesis; germacrene D biosynthesis;
CC       germacrene D from farnesyl diphosphate: step 1/1.
CC   -!- DOMAIN: Consists of 2 homologous sesquiterpene synthase domains. The
CC       Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for the catalytic
CC       activity, presumably through binding to Mg(2+).
CC       {ECO:0000269|PubMed:12556563, ECO:0000269|PubMed:12563033}.
CC   -!- MISCELLANEOUS: The earthy odorant geosmin is also responsible for the
CC       'off-flavor' of contaminated drinking water, wines, and other
CC       foodstuffs.
CC   -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether the initial Met is cleaved or not.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=The earth's perfume - Issue
CC       35 of June 2003;
CC       URL="https://web.expasy.org/spotlight/back_issues/035";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AL939126; CAB41566.1; -; Genomic_DNA.
DR   PIR; T35865; T35865.
DR   RefSeq; NP_630182.1; NC_003888.3.
DR   RefSeq; WP_011030632.1; NZ_VNID01000009.1.
DR   PDB; 5DW7; X-ray; 3.20 A; A=1-366.
DR   PDB; 5DZ2; X-ray; 2.11 A; A/B=1-338.
DR   PDBsum; 5DW7; -.
DR   PDBsum; 5DZ2; -.
DR   AlphaFoldDB; Q9X839; -.
DR   SMR; Q9X839; -.
DR   STRING; 100226.gene:17763732; -.
DR   PaxDb; 100226-SCO6073; -.
DR   PATRIC; fig|100226.15.peg.6175; -.
DR   eggNOG; ENOG502Z881; Bacteria.
DR   HOGENOM; CLU_372108_0_0_11; -.
DR   InParanoid; Q9X839; -.
DR   OrthoDB; 2989600at2; -.
DR   BioCyc; MetaCyc:MONOMER-14022; -.
DR   BRENDA; 4.1.99.16; 5998.
DR   BRENDA; 4.2.3.22; 5998.
DR   SABIO-RK; Q9X839; -.
DR   UniPathway; UPA00209; -.
DR   UniPathway; UPA00283; UER00583.
DR   UniPathway; UPA00285; UER00584.
DR   Proteomes; UP000001973; Chromosome.
DR   GO; GO:0034004; F:germacradienol synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0052577; F:germacrene-D synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   CDD; cd00687; Terpene_cyclase_nonplant_C1; 2.
DR   Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 2.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR034686; Terpene_cyclase-like_2.
DR   PANTHER; PTHR35201; TERPENE SYNTHASE; 1.
DR   PANTHER; PTHR35201:SF4; TERPENE SYNTHASE; 1.
DR   Pfam; PF19086; Terpene_syn_C_2; 2.
DR   SFLD; SFLDS00005; Isoprenoid_Synthase_Type_I; 2.
DR   SFLD; SFLDG01020; Terpene_Cyclase_Like_2; 2.
DR   SUPFAM; SSF48576; Terpenoid synthases; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Lyase; Magnesium; Metal-binding;
KW   Reference proteome; Repeat.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:12556563"
FT   CHAIN           2..726
FT                   /note="Germacradienol/geosmin synthase"
FT                   /id="PRO_0000247895"
FT   REGION          2..354
FT                   /note="Germacradienol/germacrene D synthase"
FT   REGION          355..726
FT                   /note="Geosmin synthase"
FT   MOTIF           86..91
FT                   /note="DDXXD motif 1; degenerate"
FT   MOTIF           455..459
FT                   /note="DDXXD motif 2; degenerate"
FT   BINDING         86
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         91
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         267
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         271
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         276
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         455
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         598
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         602
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         606
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   HELIX           23..37
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   STRAND          43..45
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           48..54
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           56..63
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           69..92
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   TURN            93..97
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           99..108
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           109..112
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           127..139
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           140..142
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           145..171
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           177..187
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           190..200
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           206..209
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           212..239
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           247..255
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           259..282
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           284..291
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           296..320
FT                   /evidence="ECO:0007829|PDB:5DZ2"
FT   HELIX           324..326
FT                   /evidence="ECO:0007829|PDB:5DW7"
SQ   SEQUENCE   726 AA;  81474 MW;  CB332AC7840EB81E CRC64;
     MTQQPFQLPH FYLPHPARLN PHLDEARAHS TTWAREMGML EGSGVWEQSD LEAHDYGLLC
     AYTHPDCDGP ALSLITDWYV WVFFFDDHFL EKYKRSQDRL AGKAHLDRLP LFMPLDDAAG
     MPEPRNPVEA GLADLWTRTV PAMSADWRRR FAVATEHLLN ESMWELSNIN EGRVANPVEY
     IEMRRKVGGA PWSAGLVEYA TAEVPAAVAG TRPLRVLMET FSDAVHLRND LFSYQREVED
     EGELSNGVLV LETFFGCTTQ EAADLVNDVL TSRLHQFEHT AFTEVPAVAL EKGLTPLEVA
     AVGAYTKGLQ DWQSGGHEWH MRSSRYMNKG ERPLAGWQAL TGPGTSAADV GALLADAVAQ
     RARSYTYVPF QKVGPSVIPD IRMPYPLELS PALDGARRHL SEWCREMGIL SEGVWDEDKL
     ESCDLPLCAA GLDPDATQDQ LDLASGWLAF GTYGDDYYPL VYGHRRDLAA ARLTTTRLSD
     CMPLDGEPVP PPGNAMERSL IDLWVRTTAG MTPEERRPLK KAVDDMTEAW LWELSNQIQN
     RVPDPVDYLE MRRATFGSDL TLGLCRAGHG PAVPPEVYRS GPVRSLENAA IDYACLLNDV
     FSYQKEIEYE GEIHNAVLVV QNFFGVDYPA ALGVVQDLMN QRMRQFEHVV AHELPVVYDD
     FQLSEEARTV MRGYVTDLQN WMAGILNWHR NVPRYKAEYL AGRTHGFLPD RIPAPPVPRS
     SPALTH
//