ID   QNN1_EMEVA              Reviewed;         746 AA.
AC   A0A1Y1C7Q5;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 1.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=Quiannulatene synthase {ECO:0000303|PubMed:27447198};
DE            Short=QS {ECO:0000303|PubMed:27447198};
DE   AltName: Full=Bifunctional sesterterpene synthase EvQS {ECO:0000303|PubMed:27447198};
DE   AltName: Full=Quiannulatic acid biosynthesis cluster protein EvQS {ECO:0000303|PubMed:27447198};
DE   Includes:
DE     RecName: Full=Sesterterpenoid synthase {ECO:0000303|PubMed:27447198};
DE              EC=4.2.3.- {ECO:0000303|PubMed:27447198};
DE     AltName: Full=Geranylgeranyl diphosphate synthase {ECO:0000250|UniProtKB:C9K2Q3};
DE              Short=GGDP synthase {ECO:0000250|UniProtKB:C9K2Q3};
DE              Short=GGS {ECO:0000250|UniProtKB:C9K2Q3};
DE              EC=2.5.1.29 {ECO:0000250|UniProtKB:C9K2Q3};
GN   Name=EvQS {ECO:0000303|PubMed:27447198};
OS   Emericella variicolor (Aspergillus stellatus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=1549217;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=ATCC 12069 / CBS 136.55 / IMI 60316 / NBRC 32302;
RX   PubMed=27447198; DOI=10.1021/jacs.6b05799;
RA   Okada M., Matsuda Y., Mitsuhashi T., Hoshino S., Mori T., Nakagawa K.,
RA   Quan Z., Qin B., Zhang H., Hayashi F., Kawaide H., Abe I.;
RT   "Genome-based Discovery of an unprecedented cyclization mode in fungal
RT   sesterterpenoid biosynthesis.";
RL   J. Am. Chem. Soc. 138:10011-10018(2016).
CC   -!- FUNCTION: Bifunctional sesterterpene synthase; part of the gene cluster
CC       that mediates the biosynthesis of the pentacyclic sesterterpene
CC       quiannulatic acid (PubMed:27447198). The first step of the pathway is
CC       performed by the sesterterpene synthase (QS) that possesses both prenyl
CC       transferase and terpene cyclase activity, converting isopentenyl
CC       diphosphate and dimethylallyl diphosphate into geranylfarnesyl
CC       diphosphate (GFPP) and further converting GFPP into quiannulatene via
CC       an unprecedented cyclization mode which involves three rounds of
CC       hydride shifts and two successive C-C bond migrations to construct the
CC       5-6-5-5-5 fused ring (PubMed:27447198). The cytochrome P450
CC       monooxygenase Qnn-P450 then oxidizes quiannulatene at C-19 in 3
CC       successive reactions to afford quiannulatic acid (PubMed:27447198).
CC       {ECO:0000269|PubMed:27447198}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate =
CC         (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
CC         Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756,
CC         ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29;
CC         Evidence={ECO:0000269|PubMed:27447198};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC         Evidence={ECO:0000269|PubMed:27447198};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E,10E,14E)-geranylfarnesyl diphosphate = diphosphate +
CC         quiannulatene; Xref=Rhea:RHEA:66864, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:57907, ChEBI:CHEBI:167518;
CC         Evidence={ECO:0000269|PubMed:27447198};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66865;
CC         Evidence={ECO:0000269|PubMed:27447198};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q12051,
CC         ECO:0000250|UniProtKB:Q40577};
CC       Note=Binds 4 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051,
CC       ECO:0000250|UniProtKB:Q40577};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:27447198}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the terpene synthase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the FPP/GGPP synthase
CC       family. {ECO:0000305}.
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; LC155210; BAX76657.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1Y1C7Q5; -.
DR   SMR; A0A1Y1C7Q5; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0004311; F:farnesyltranstransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00685; Trans_IPPS_HT; 1.
DR   Gene3D; 1.10.600.10; -; 2.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR000092; Polyprenyl_synt.
DR   InterPro; IPR033749; Polyprenyl_synt_CS.
DR   Pfam; PF00348; polyprenyl_synt; 1.
DR   SUPFAM; SSF48576; SSF48576; 2.
DR   PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR   PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE   3: Inferred from homology;
KW   Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW   Multifunctional enzyme; Transferase.
FT   CHAIN           1..746
FT                   /note="Quiannulatene synthase"
FT                   /id="PRO_0000452689"
FT   REGION          1..336
FT                   /note="Sesterterpenoid synthase"
FT                   /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT   REGION          338..746
FT                   /note="Geranylfarnesyl diphosphate synthase"
FT                   /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT   BINDING         95
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q40577"
FT   BINDING         95
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q40577"
FT   BINDING         465
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         468
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         497
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         504
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         504
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         508
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         508
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         513
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         514
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         591
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         592
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         628
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         635
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
FT   BINDING         645
FT                   /ligand="dimethylallyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:57623"
FT                   /evidence="ECO:0000250|UniProtKB:Q12051"
SQ   SEQUENCE   746 AA;  84284 MW;  EC1290B3804175E7 CRC64;
     MASEVIVISD HARKEAGTVS VFPVLIHTDY ARVIEDVRKV EDQFNSEMKT SIDTKTTADF
     PELGLAHVTA FTIPYCRPDR LSIMTRLTEI TFFNDDYYDD AGVEKILDYN NHLRECFGGR
     AEDELTKASA VTKSKQLQAS VLVEMHYIDS ELARDMMLTY NRILEVTSLG KNAGLKSLDE
     YLPFRIGNSG IEVYQDMSCF GMGVKLTKEE KEKLDPIVIA AHNSTTLIND YHSWPKEVRK
     YFNEVQATGK ADLPVNAVCI FMQTEGLSEQ ASRQRVREEI IAQQKSHLAM IQDLVEQEGP
     LPEKYYMYFK AAQYTASGSE YWAAITSRYP TKTELNQPEV IIVDGELKYE SSEIQQTPKQ
     IATTFNGIPE SAKSIIESKV NGTSAHIPDI RHSPADGAQT HHLISDGQFR EVINGHANVH
     TNGKANGTSQ GEDLEVYEVT TGNFQRAPED TVLAPYQYIA SLPSKNIRNK FIDALNLWLG
     VPPLALSSIK RIVEYLHHSS LMLDDIEDNS TLRRGKPCTH MLYGNAQTIN AANYAFVSAF
     AEVQNLQSPS AITIFIREVQ NMHRGQSLDL SWKYHTHCPT VDEYMMMVDN KTGAMFRLCV
     QLMQAESSVP CQKITQSDFI TQLGRYFQIR DDYQNLVSSE YTTQKGFCED LDEGKISLPL
     IYTIMDSSPE ASVVKGIFHH RLREGGLPLH LKEYILSQME EKGALSATHS LLQKMQKELI
     EGLHRVEETF GSKNALVELM LRRLWV