OBLA_ASPCL
ID OBLA_ASPCL Reviewed; 718 AA.
AC A1C8C3;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Ophiobolin F synthase oblA {ECO:0000303|PubMed:23324037};
DE Short=acOS {ECO:0000303|PubMed:23324037};
DE AltName: Full=Bifunctional sesterterpene synthase oblA {ECO:0000303|PubMed:23324037};
DE AltName: Full=Ophiobolin biosynthesis cluster protein A {ECO:0000303|PubMed:27116000};
DE Includes:
DE RecName: Full=Ophiobolin F cyclase {ECO:0000303|PubMed:23324037};
DE EC=4.2.3.145 {ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:23324037};
DE Short=GGDP synthase {ECO:0000303|PubMed:23324037};
DE Short=GGS {ECO:0000303|PubMed:23324037};
DE EC=2.5.1.29 {ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase {ECO:0000303|PubMed:23324037};
DE Short=GFDP synthase {ECO:0000303|PubMed:23324037};
DE EC=2.5.1.81 {ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
GN Name=oblA {ECO:0000303|PubMed:27116000}; ORFNames=ACLA_076850;
OS Aspergillus clavatus (strain ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 /
OS NRRL 1 / QM 1276 / 107).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=344612;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
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 CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=23324037; DOI=10.1021/ol303408a;
RA Chiba R., Minami A., Gomi K., Oikawa H.;
RT "Identification of ophiobolin F synthase by a genome mining approach: a
RT sesterterpene synthase from Aspergillus clavatus.";
RL Org. Lett. 15:594-597(2013).
RN [3]
RP FUNCTION, AND PATHWAY.
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).
RN [4]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=28362483; DOI=10.1021/acs.biochem.7b00137;
RA Pemberton T.A., Chen M., Harris G.G., Chou W.K., Duan L., Koeksal M.,
RA Genshaft A.S., Cane D.E., Christianson D.W.;
RT "Exploring the influence of domain architecture on the catalytic function
RT of diterpene synthases.";
RL Biochemistry 56:2010-2023(2017).
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:23324037, PubMed:27116000, PubMed:28362483). The first step of
CC the pathway is performed by the sesterterpene synthase oblA that
CC possesses both prenyl transferase and terpene cyclase activity,
CC converting isopentenyl diphosphate and dimethylallyl diphosphate into
CC geranylfarnesyl diphosphate (GFPP) and further converting GFPP into
CC ophiobolin F, respectively (PubMed:23324037). Other sesterterpenoids
CC (C(25) terpenoids) are found as minor products of oblA
CC (PubMed:23324037). It is expected that ophiobolin F is then oxidized to
CC ophiobolin A via ophiobolin C and ophiobolin B intermediates by the
CC combined action of the cytochrome P450 monooxygenase oblB and the FAD-
CC dependent oxidoreductase oblC (Probable). Although oblB catalyzes
CC multistep oxygenations at C5 and C21/C7 in a relatively efficient
CC manner, it is unable to convert ophiobolin F to ophiobolin C and
CC produces instead several unexpected derivatives (PubMed:27116000).
CC {ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:27116000,
CC ECO:0000269|PubMed:28362483, 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:23324037, ECO:0000269|PubMed:28362483};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
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:23324037,
CC ECO:0000269|PubMed:28362483};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25695;
CC Evidence={ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
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:23324037,
CC ECO:0000269|PubMed:28362483};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41553;
CC Evidence={ECO:0000269|PubMed:23324037, ECO:0000269|PubMed:28362483};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.024 uM for geranylgeranyl diphosphate (GGDP)
CC {ECO:0000269|PubMed:28362483};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:23324037}.
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:28362483}.
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; DS027045; EAW14644.1; -; Genomic_DNA.
DR RefSeq; XP_001276070.1; XM_001276069.1.
DR AlphaFoldDB; A1C8C3; -.
DR SMR; A1C8C3; -.
DR STRING; 5057.CADACLAP00006804; -.
DR EnsemblFungi; EAW14644; EAW14644; ACLA_076850.
DR GeneID; 4708281; -.
DR KEGG; act:ACLA_076850; -.
DR VEuPathDB; FungiDB:ACLA_076850; -.
DR eggNOG; KOG0777; Eukaryota.
DR HOGENOM; CLU_014015_10_0_1; -.
DR OMA; WHGLVTF; -.
DR OrthoDB; 981769at2759; -.
DR BioCyc; MetaCyc:MON-19519; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
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; 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; Transferase.
FT CHAIN 1..718
FT /note="Ophiobolin F synthase oblA"
FT /id="PRO_0000430745"
FT REGION 1..320
FT /note="(7Z)-ophiobola-7,19-dien-3-ol synthase"
FT /evidence="ECO:0000269|PubMed:28362483"
FT REGION 321..718
FT /note="Geranylfarnesyl diphosphate synthase"
FT /evidence="ECO:0000269|PubMed:28362483"
FT REGION 346..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 93..97
FT /note="DDXXD 1"
FT /evidence="ECO:0000305|PubMed:28362483"
FT MOTIF 224..232
FT /note="NSE/DTE"
FT /evidence="ECO:0000305|PubMed:28362483"
FT MOTIF 468..472
FT /note="DDXXD 2"
FT /evidence="ECO:0000305|PubMed:28362483"
FT COMPBIAS 346..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..391
FT /note="Polar 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 180..183
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 228..232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 311..312
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 429
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 432
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 461
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 468
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 468
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 472
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 472
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 477
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 478
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 555
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 556
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 594
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 601
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"
SQ SEQUENCE 718 AA; 81603 MW; ACDF491AA26EFC9C CRC64;
MACKYSTLID SSLYDREGLC PGIDLRRHVA GELEEVGAFR AQEDWRRLVG PLPKPYAGLL
GPDFSFITGA VPECHPDRME IVAYALEFGF MHDDVIDTDV NHASLDEVGH TLDQSRTGKI
EDKGSDGKRQ MVTQIIREMM AIDPERAMTV AKSWASGVRH SSRRKEDTNF KALEQYIPYR
ALDVGYMLWH GLVTFGCAIT IPNEEEEEAK RLIIPALVQA SLLNDLFSFE KEKNDANVQN
AVLIVMNEHG CSEEEARDIL KKRIRLECAN YLRNVKETNA RADVSDELKR YINVMQYTLS
GNAAWSTNCP RYNGPTKFNE LQLLRSEHGL AKYPSRWSQE NRTSGLVEGD CHESKPNELK
RKRNGVSVDD EMRTNGTNGA KKPAHVSQPS TDSIVLEDMV QLARTCDLPD LSDTVILQPY
RYLTSLPSKG FRDQAIDSIN KWLKVPPKSV KMIKDVVKML HSASLMLDDL EDNSPLRRGK
PSTHSIYGMA QTVNSATYQY ITATDITAQL QNSETFHIFV EELQQLHVGQ SYDLYWTHNT
LCPTIAEYLK MVDMKTGGLF RMLTRMMIAE SPVVDKVPNS DMNLFSCLIG RFFQIRDDYQ
NLASADYAKA KGFAEDLDEG KYSFTLIHCI QTLESKPELA GEMMQLRAFL MKRRHEGKLS
QEAKQEVLVT MKKTESLQYT LSVLRELHSE LEKEVENLEA KFGEENFTLR VMLELLKV
