NFSS_NEOFI
ID NFSS_NEOFI Reviewed; 764 AA.
AC A1DN30;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Sesterfisherol synthase {ECO:0000303|PubMed:26332841};
DE Short=SS {ECO:0000303|PubMed:26332841};
DE AltName: Full=Sesterfisheric acid biosynthesis cluster protein NfSS {ECO:0000303|PubMed:26332841};
DE Includes:
DE RecName: Full=Terpene cyclase {ECO:0000303|PubMed:26332841};
DE EC=4.2.3.176 {ECO:0000269|PubMed:26332841, ECO:0000269|PubMed:29410538};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:26332841};
DE Short=GGDP synthase {ECO:0000303|PubMed:26332841};
DE Short=GGS {ECO:0000303|PubMed:26332841};
DE EC=2.5.1.29 {ECO:0000269|PubMed:26332841};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase;
DE Short=GFDP synthase {ECO:0000303|PubMed:26332841};
DE EC=2.5.1.81 {ECO:0000269|PubMed:26332841};
GN Name=NfSS {ECO:0000303|PubMed:26332841}; ORFNames=NFIA_055500;
OS Neosartorya fischeri (strain ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164
OS / JCM 1740 / NRRL 181 / WB 181) (Aspergillus fischerianus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=331117;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164 / JCM 1740 / NRRL 181
RC / WB 181;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26332841; DOI=10.1021/jacs.5b08319;
RA Ye Y., Minami A., Mandi A., Liu C., Taniguchi T., Kuzuyama T., Monde K.,
RA Gomi K., Oikawa H.;
RT "Genome mining for sesterterpenes using bifunctional terpene synthases
RT reveals a unified intermediate of di/sesterterpenes.";
RL J. Am. Chem. Soc. 137:11846-11853(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-191.
RX PubMed=29410538; DOI=10.1038/s41598-018-20916-x;
RA Sato H., Narita K., Minami A., Yamazaki M., Wang C., Suemune H., Nagano S.,
RA Tomita T., Oikawa H., Uchiyama M.;
RT "Theoretical Study of Sesterfisherol Biosynthesis: Computational Prediction
RT of Key Amino Acid Residue in Terpene Synthase.";
RL Sci. Rep. 8:2473-2473(2018).
CC -!- FUNCTION: Bifunctional terpene synthase; part of the gene cluster that
CC mediates the biosynthesis of sesterfisheric acid (PubMed:26332841). The
CC bifunctional terpene synthase NfSS converts DMAPP and IPP, and also
CC GGPP, into sesterfisherol (PubMed:26332841, PubMed:29410538). The C-
CC terminal prenyltransferase (PT) domain of NfSS catalyzes formation of
CC GFPP, whereas the N-terminal terpene cyclase (TC) domain catalyzes the
CC cyclization of GFPP to sesterfisherol (PubMed:26332841,
CC PubMed:29410538). The cyotochrome P450 monooxygenase NfP450 then
CC catalyzes oxidative modifications of sesterfisherol into sesterfisheric
CC acid (PubMed:26332841). {ECO:0000269|PubMed:26332841,
CC ECO:0000269|PubMed:29410538}.
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:26332841};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:26332841};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + isopentenyl
CC diphosphate = (2E,6E,10E,14E)-geranylfarnesyl diphosphate +
CC diphosphate; Xref=Rhea:RHEA:25694, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57907, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769;
CC EC=2.5.1.81; Evidence={ECO:0000269|PubMed:26332841};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25695;
CC Evidence={ECO:0000269|PubMed:26332841};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E,14E)-geranylfarnesyl diphosphate + H2O =
CC diphosphate + sesterfisherol; Xref=Rhea:RHEA:54068,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:33019, ChEBI:CHEBI:57907,
CC ChEBI:CHEBI:138046; EC=4.2.3.176;
CC Evidence={ECO:0000269|PubMed:26332841, ECO:0000269|PubMed:29410538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54069;
CC Evidence={ECO:0000269|PubMed:26332841};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WEV7};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:26332841}.
CC -!- SUBUNIT: Hexamer. {ECO:0000250|UniProtKB:A2PZA5}.
CC -!- DOMAIN: The conserved DDXXD motifs as well as the NSE/DTE motif are
CC important for the catalytic activity, presumably through binding to
CC Mg(2+). {ECO:0000305|PubMed:26332841}.
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}.
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DR EMBL; DS027698; EAW16201.1; -; Genomic_DNA.
DR RefSeq; XP_001258098.1; XM_001258097.1.
DR SMR; A1DN30; -.
DR STRING; 36630.CADNFIAP00004248; -.
DR EnsemblFungi; EAW16201; EAW16201; NFIA_055500.
DR GeneID; 4584613; -.
DR KEGG; nfi:NFIA_055500; -.
DR VEuPathDB; FungiDB:NFIA_055500; -.
DR eggNOG; KOG0777; Eukaryota.
DR HOGENOM; CLU_014015_10_0_1; -.
DR OMA; GMEHERA; -.
DR OrthoDB; 981769at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000006702; Unassembled WGS sequence.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Reference proteome; Repeat; Transferase.
FT CHAIN 1..764
FT /note="Sesterfisherol synthase"
FT /id="PRO_0000453639"
FT REGION 2..331
FT /note="Terpene cyclase"
FT /evidence="ECO:0000305|PubMed:26332841"
FT REGION 332..759
FT /note="Prenyltransferase"
FT /evidence="ECO:0000305|PubMed:26332841"
FT REGION 347..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 95..99
FT /note="DDXXD 1"
FT /evidence="ECO:0000305|PubMed:26332841"
FT MOTIF 231..239
FT /note="NSE/DTE"
FT /evidence="ECO:0000305|PubMed:26332841"
FT MOTIF 515..519
FT /note="DDXXD 2"
FT /evidence="ECO:0000305|PubMed:26332841"
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 95
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 187..190
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 235..239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 324..325
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 476
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 479
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 508
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 515
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 515
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 519
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 519
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 524
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 525
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 602
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 603
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 638
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"
FT BINDING 655
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 665
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT MUTAGEN 191
FT /note="F->A: Produces novel sesterterpenes, but not
FT sesterfisherol."
FT /evidence="ECO:0000269|PubMed:29410538"
SQ SEQUENCE 764 AA; 87565 MW; EC539F20E49E8D9B CRC64;
MEVWEHSRPI ADDTIKKTPS FTTLPIRINK QNDVADAATR RALRDWDYYL HDGLAERALI
SISELGNLGA FAYPEVPPER LAIVTYLTDL GILHDDGYEA MDMDQARTEH REFGALFDPH
EQLPSRRGTR AAKLKKLVSQ ILLEAIRIDR DMGMYMFDMY NKGWLSVAGG EGKVPQFKSV
EEYQAYRRDD FGIRAFWPMV EFGMAMRLSD EDKKLIEPVM EPIDKAIIWT NDYWSFDREY
HESITNGSRL TNVVEVVRQI ENKSIDEAKA AVRQLLVNLE QQYLERKRAI YAQNPSIPSH
LRKWIEVVGI TVAGTHFWAS CSPRHHAWRN NSRNGLKPAN HVAAPTLITP SNNLNSSKGS
EEQMQDSDNG TRTQMCPAND HEVMQLNAKL SLGKQDGGHA MRAALALLSR AAEQCESLFD
GMEHERARLL QSGEEKARLS WEGRSKGSQE LEHSWYKPAK TALQAPIHYI CSMPSKGVRS
RMIEAFNYWL EVDETSLTKI RRLVDLLHNA SLILDDIEDH SPKRRGRPAT HTIFGHSQAI
NSANFMFVQA VQVARQFRNP NAVDILLEEL ENLYLGQSWD LDWKYKLRCP SPSEYLNMVD
NKTGGLFRLL LRLMQAERKG TTEVDLDGLT VLFGRFFQIR DDYMNLRSGL YTEQKGFCED
LDEGKFSYPI VVCVANHADF RDLIDGVFRQ RPTAITSGMQ PLAPEIKRYV VEYLNTSGTF
QHCREFLMQL ESLIESEIDR IEKVTNEANP MLRLLLEKLS VKEN
