STTA_ASPTE
ID STTA_ASPTE Reviewed; 778 AA.
AC P9WEV2;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Preaspterpenacid I synthase sttA {ECO:0000303|PubMed:34085529};
DE Includes:
DE RecName: Full=Sesterterpenoid synthase {ECO:0000303|PubMed:34085529};
DE EC=4.2.3.- {ECO:0000269|PubMed:34085529};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase {ECO:0000303|PubMed:34085529};
DE Short=GFDP synthase {ECO:0000303|PubMed:34085529};
DE EC=2.5.1.- {ECO:0000269|PubMed:34085529};
DE AltName: Full=Aspterpenacid biosynthesis cluster protein sttA {ECO:0000303|PubMed:34085529};
DE AltName: Full=Ophiobolin family sesterterpenoid biosynthesis cluster protein A {ECO:0000303|PubMed:28604695};
GN Name=sttA {ECO:0000303|PubMed:28604695};
OS Aspergillus terreus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=33178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=ATCC 20542 / MF4845;
RX PubMed=28604695; DOI=10.1038/nchembio.2408;
RA Clevenger K.D., Bok J.W., Ye R., Miley G.P., Verdan M.H., Velk T., Chen C.,
RA Yang K., Robey M.T., Gao P., Lamprecht M., Thomas P.M., Islam M.N.,
RA Palmer J.M., Wu C.C., Keller N.P., Kelleher N.L.;
RT "A scalable platform to identify fungal secondary metabolites and their
RT gene clusters.";
RL Nat. Chem. Biol. 13:895-901(2017).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=34085529; DOI=10.1021/acs.orglett.1c01361;
RA Jiang L., Zhang X., Sato Y., Zhu G., Minami A., Zhang W., Ozaki T., Zhu B.,
RA Wang Z., Wang X., Lv K., Zhang J., Wang Y., Gao S., Liu C., Hsiang T.,
RA Zhang L., Oikawa H., Liu X.;
RT "Genome-based discovery of enantiomeric pentacyclic sesterterpenes
RT catalyzed by fungal bifunctional terpene synthases.";
RL Org. Lett. 23:4645-4650(2021).
CC -!- FUNCTION: Sesterterpenoid synthase; part of the gene cluster that
CC mediates the biosynthesis of aspterpenacids (PubMed:28604695,
CC PubMed:34085529). Performs both prenyl transferase and terpene cyclase
CC activity, converting isopentenyl diphosphate and dimethylallyl
CC diphosphate into geranylfarnesyl diphosphate (GFPP) and then converting
CC GFPP into preaspterpenacid I (PubMed:34085529). C22-oxidative
CC modification of preaspterpenacid I by the cytochrome P450 monooxygenase
CC sttB then leads to preaspterpenacid II. It has still to be determined
CC how preaspterpenacid II is further modified to produce aspterpenacids
CC (Probable). {ECO:0000269|PubMed:28604695, ECO:0000269|PubMed:34085529,
CC ECO:0000305|PubMed:34085529}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + 4 isopentenyl diphosphate =
CC (2E,6E,10E,14E)-geranylfarnesyl diphosphate + 4 diphosphate;
CC Xref=Rhea:RHEA:66860, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623,
CC ChEBI:CHEBI:57907, ChEBI:CHEBI:128769;
CC Evidence={ECO:0000269|PubMed:34085529};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66861;
CC Evidence={ECO:0000269|PubMed:34085529};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28604695, ECO:0000269|PubMed:34085529}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of the ophiobolin family
CC sesterterpenoid. {ECO:0000269|PubMed:28604695}.
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; KX449366; AQM58281.1; -; Genomic_DNA.
DR AlphaFoldDB; P9WEV2; -.
DR SMR; P9WEV2; -.
DR VEuPathDB; FungiDB:ATEG_03568; -.
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.
PE 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Transferase.
FT CHAIN 1..778
FT /note="Preaspterpenacid I synthase sttA"
FT /id="PRO_0000450606"
FT REGION 4..359
FT /note="Sesterterpenoid synthase"
FT /evidence="ECO:0000250|UniProtKB:C9K2Q3"
FT REGION 211..214
FT /note="Substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT REGION 259..263
FT /note="Substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT REGION 350..351
FT /note="Substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT REGION 360..774
FT /note="Geranylfarneyl diphosphate synthase"
FT /evidence="ECO:0000250|UniProtKB:C9K2Q3"
FT REGION 423..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..445
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 255
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 493
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 496
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
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 532
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 532
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 536
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 536
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 541
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 542
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 619
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 620
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 657
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 664
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 674
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 778 AA; 88150 MW; 1AC94C0161BAC7E8 CRC64;
MDTISDVMKH CVPINYDDYD PLPADHFSTY PVFCSKATAE AIEASAEFTR KWKRACEVDG
LHQDKLSFQA CTTHLGHYNQ WAYPDCVPER VSLNAVLSDC AFFWDGMSPV TGRSANVMIT
SPVDVSDSIS AEKMNELTQD FGIAMLSELQ SGRRIEPKFE INKMAVQVIR DFIAVDPFTG
IGHLKEWKGH LDAQKKSTHN NMSWEKYVEH RVNESGGNWG ISVGCWTNDI RISDEEKESV
KYLTQLACAG GILGNDYYSF PKEFDEHHRS GTLDRIQNGV ALLMREYGYT EEEAKEIIKK
EVIIREKKWM DGFNAWSRQA GPETGEIRRY LVMTMALMSG SMFWMSHAGR YHRTDLATTA
EDRATLIGKS RGALRVLEGY PPPKNLEGIV REPLASAVQD DNGHVQHEDA VADSSVRNGV
HDAFKKSNPR NGKQNGTEGS KGTFTNGGYV QPAKLQQHCT SINSMAIYTA PFQEAAGDIC
DAPYGYIDSL PSKKNRNKLL DLLNDWLQVP PSSLKRIKNI VHMLHNSSLM LDDIEDASAL
RRGQPATHTF YGISQTINSA NYIYVHVVDE VTRLYNPECI NIFVDELRNL HRGQSLDLYW
RHHARCPSME EYIVMVDNKT GGLFRLMLRL LTAESSISRP FDTALSRLLT LTGRYYQIRD
DYLNLASADY ESKKGFCEDF DEGKFSLPLI HLLSHTRYPD RITSALFNRK PGTNLPYEMK
RYILAEMEEV QTLAYSQDVL KYLHEELMHA LDEAENRLGA NDGVRMMLLG MGPKLLLC
