OBLA_EMEVA
ID OBLA_EMEVA Reviewed; 728 AA.
AC A0A1V1FVQ6;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Ophiobolin F synthase oblA {ECO:0000303|PubMed:27116000};
DE AltName: Full=Bifunctional sesterterpene synthase oblA {ECO:0000303|PubMed:27116000};
DE AltName: Full=Ophiobolin biosynthesis cluster protein A {ECO:0000303|PubMed:27116000};
DE Includes:
DE RecName: Full=Ophiobolin F cyclase {ECO:0000303|PubMed:27116000};
DE EC=4.2.3.145 {ECO:0000269|PubMed:27116000};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:27116000};
DE Short=GGDP synthase {ECO:0000303|PubMed:27116000};
DE Short=GGS {ECO:0000303|PubMed:27116000};
DE EC=2.5.1.29 {ECO:0000269|PubMed:27116000};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase {ECO:0000303|PubMed:27116000};
DE Short=GFDP synthase {ECO:0000303|PubMed:27116000};
DE EC=2.5.1.81 {ECO:0000269|PubMed:27116000};
GN Name=oblA {ECO:0000303|PubMed:27116000};
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 CATALYTIC ACTIVITY.
RC STRAIN=GF10;
RX PubMed=27116000; DOI=10.1021/acs.orglett.6b00552;
RA Narita K., Chiba R., Minami A., Kodama M., Fujii I., Gomi K., Oikawa H.;
RT "Multiple oxidative modifications in the ophiobolin biosynthesis: P450
RT oxidations found in genome mining.";
RL Org. Lett. 18:1980-1983(2016).
CC -!- FUNCTION: Bifunctional sesterterpene synthase; part of the gene cluster
CC that mediates the biosynthesis of the sesterterpenes ophiobolins,
CC fungal phytotoxins with potential anti-cancer activities
CC (PubMed:27116000). The first step of the pathway is performed by the
CC sesterterpene synthase oblA that possesses both prenyl transferase and
CC terpene cyclase activity, converting isopentenyl diphosphate and
CC dimethylallyl diphosphate into geranylfarnesyl diphosphate (GFPP) and
CC further converting GFPP into ophiobolin F, respectively (By
CC similarity). Other sesterterpenoids (C(25) terpenoids) are found as
CC minor products of oblA (By similarity). The cytochrome P450
CC monooxygenase oblB then catalyzes a four-step oxidative transformation
CC of ophiobolin F to yield ophiobolin C (PubMed:27116000). The function
CC of the cytochrome P450 monooxygenase oblE has still to be determined
CC (Probable). {ECO:0000250|UniProtKB:A1C8C3, ECO:0000269|PubMed:27116000,
CC ECO:0000305|PubMed:27116000}.
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:27116000};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:27116000};
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:27116000};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25695;
CC Evidence={ECO:0000269|PubMed:27116000};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E,14E)-geranylfarnesyl diphosphate + H2O =
CC diphosphate + ophiobolin F; Xref=Rhea:RHEA:41552, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57907, ChEBI:CHEBI:78293;
CC EC=4.2.3.145; Evidence={ECO:0000269|PubMed:27116000};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41553;
CC Evidence={ECO:0000269|PubMed:27116000};
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:0000305|PubMed:27116000}.
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:0000250|UniProtKB:A1C8C3}.
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; LC127211; BAX09282.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1V1FVQ6; -.
DR SMR; A0A1V1FVQ6; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0004311; F:farnesyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0044687; F:geranylfarnesyl diphosphate synthase 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 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; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Transferase.
FT CHAIN 1..728
FT /note="Ophiobolin F synthase oblA"
FT /id="PRO_0000451168"
FT REGION 1..322
FT /note="(7Z)-ophiobola-7,19-dien-3-ol synthase"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT REGION 323..728
FT /note="Geranylfarnesyl diphosphate synthase"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT REGION 362..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 93..97
FT /note="DDXXD 1"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT MOTIF 226..234
FT /note="NSE/DTE"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT MOTIF 478..482
FT /note="DDXXD 2"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT COMPBIAS 371..387
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 93
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 182..185
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 230..234
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 313..314
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 439
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 442
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 471
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 478
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 478
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 482
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 482
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 487
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 488
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 565
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 566
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 604
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 611
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 621
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 631
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 728 AA; 82233 MW; 72C167AC9BF8B412 CRC64;
MEYKYSTIVD KSKWDPEGLT EGIPLRRHEA GDLEEVGSFR VQEDWRRLVG PLENPYRGSL
GPEISFITYT VPECLPERLE AISYSLDYGF MHDDEIDLNI ASAELSDVGG ALKQGGATGK
IDEGKSSSGK RKMAAQLLRE MMALDPERAM ALAKSWAQGV QHSARRVEEK DWKSLDEYIP
FRCMDLGYMH WHGLVTFGCA ITVPEEEEEE RRRLLEPAVI ACMMTNDLFS YEKEKNDNNP
QNAVTVIMKI NKCGEEEAKE VCKKRIRVEC AKYAQIVKET LARTDISLDL KKYIEIMQYT
VSGNWAWSTQ CPRYHFPGRW NELQKLRAEH GIAKYPARYS LKERTNGVNG VNGVNGINGT
NGINGTNGVN GKRNRDEDGD ENDARINGNG FKKPALTSQG KDSFVLDDVV ALSLNLHLPD
LGDGVVLQPY RYLTSLPSKG FRDMAIDALN TWLRVPSTST STIKDLIKKL HSASLMLDDI
EDNSPLRRAK PSTHIIYGNA QTINSATYQY TEATSLAANL SNPLSLRIFL DEIQQLYIGQ
SYDLYWTHNA LCPSITEYLR MVDQKTGGLF RMLTRLMVAE SPGSNKILDR ALFPLSHLIG
RFFQIRDDYQ NLSSAEYSRQ KGFVEDLDEG KYSFTLIHCI QTVEANEALA SEMMALRAFL
IKRRVDGGLS NEAKMEVLGI MKKTKSLEYT LGVLRALQEE LEREVGRLEG KFGEENLPLR
LMVDMLKV
