AUAS_ASPUT
ID AUAS_ASPUT Reviewed; 710 AA.
AC P9WEP0; A0A889ZB43;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=Aspergildiene synthase {ECO:0000303|PubMed:33480256};
DE Short=AS {ECO:0000303|PubMed:33480256};
DE AltName: Full=Aspergilol biosynthesis cluster protein AuAS {ECO:0000303|PubMed:33480256};
DE AltName: Full=Bifunctional terpene synthase AuAS {ECO:0000303|PubMed:33480256};
DE Short=BFTS AuAS {ECO:0000303|PubMed:33480256};
DE Includes:
DE RecName: Full=Terpene cyclase {ECO:0000303|PubMed:33480256};
DE EC=4.2.3.- {ECO:0000269|PubMed:33480256};
DE Includes:
DE RecName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:33480256};
DE Short=GGDP synthase {ECO:0000303|PubMed:33480256};
DE Short=GGS {ECO:0000303|PubMed:33480256};
DE EC=2.5.1.29 {ECO:0000269|PubMed:33480256};
DE Includes:
DE RecName: Full=Geranylfarnesyl diphosphate synthase {ECO:0000303|PubMed:33480256};
DE Short=GFDP synthase {ECO:0000303|PubMed:33480256};
DE EC=2.5.1.81 {ECO:0000269|PubMed:33480256};
GN Name=AuAS {ECO:0000303|PubMed:33480256};
OS Aspergillus ustus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=40382;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, DOMAIN, PATHWAY,
RP AND BIOTECHNOLOGY.
RX PubMed=33480256; DOI=10.1021/acs.orglett.0c03996;
RA Guo J., Cai Y.S., Cheng F., Yang C., Zhang W., Yu W., Yan J., Deng Z.,
RA Hong K.;
RT "Genome mining Reveals a multiproduct sesterterpenoid biosynthetic gene
RT cluster in Aspergillus ustus.";
RL Org. Lett. 23:1525-1529(2021).
CC -!- FUNCTION: Bifunctional terpene synthase; part of the gene cluster that
CC mediates the biosynthesis of aspergiltriene A, aspergildienes A-D and
CC aspergilols A-D (PubMed:33480256). The bifunctional terpene synthase
CC AuAS converts isopentenyl diphosphate (IPP) and dimethylallyl
CC diphosphate (DMAPP) into sesterterpenes (PubMed:33480256). The C-
CC terminal prenyltransferase (PT) domain of AuAS catalyzes formation of
CC GFPP, whereas the N-terminal terpene cyclase (TC) domain catalyzes the
CC cyclization of GFPP into 5 distinct sesterterpenes: aspergiltriene A,
CC aspergildiene A, aspergildiene B, aspergildiene C and aspergildiene D
CC (PubMed:33480256). The cytochrome P450 monooxygenase AP450 then
CC hydroxylates the aspergildienes A, B, C and D to yield the
CC corresponding sesterterpene alcohols, aspergilols A-D
CC (PubMed:33480256). {ECO:0000269|PubMed:33480256}.
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:33480256};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:33480256};
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:33480256};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25695;
CC Evidence={ECO:0000269|PubMed:33480256};
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:33480256}.
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:33480256}.
CC -!- BIOTECHNOLOGY: Aspergilol A shows a weak cytotoxicity toward MCF-7,
CC MDA-MB231, and HepG2 cancer cells lines, with an IC(50) value ranging
CC from 21.21 to 48.76 uM; whereas aspergilol B only shows a weak
CC cytotoxicity against MCF-7 cells, with an IC(50) value of 27.41 uM
CC (PubMed:33480256). None of the aspergilols have antifungal or
CC antibacterial activities (PubMed:33480256).
CC {ECO:0000269|PubMed:33480256}.
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; MW387950; QRF92542.1; -; mRNA.
DR SMR; P9WEP0; -.
DR UniPathway; UPA00213; -.
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 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 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Repeat; Transferase.
FT CHAIN 1..710
FT /note="Aspergildiene synthase"
FT /id="PRO_0000453700"
FT REGION 1..338
FT /note="Terpene cyclase"
FT /evidence="ECO:0000305|PubMed:33480256"
FT REGION 339..710
FT /note="Prenyltransferase"
FT /evidence="ECO:0000305|PubMed:33480256"
FT REGION 367..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 106..110
FT /note="DDXXD 1"
FT /evidence="ECO:0000305|PubMed:33480256"
FT MOTIF 239..247
FT /note="NSE/DTE"
FT /evidence="ECO:0000305|PubMed:33480256"
FT MOTIF 470..474
FT /note="DDXXD 2"
FT /evidence="ECO:0000305|PubMed:33480256"
FT COMPBIAS 380..400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 106
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 106
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 106
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 243..247
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 334..335
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A2PZA5"
FT BINDING 431
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 434
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 463
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 470
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 470
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 479
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 480
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 557
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 558
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 710 AA; 80231 MW; A8B085FD0924F487 CRC64;
MDAALRDICQ LSDPCDPRSF EPPIKDFFCI YPMYRSRYEA KAIQGSNEFL DGWNKAIEKD
GLRNDGRPFL GCNTIYGNYV AWAYPECLPE RAAHVAAYCD WGFFWDDATD AMSMEKNHEA
TKDLILTIMS TVGIGQKHEP LLAVNKLVVP FVLNKLAGTD GDLGLNHMKA WKAHLDGQAR
SSHANMSWEE LKQHRLVEGG PEWAIRLGAW GAGIRCTAEE IESVREIIDI GGIAGVLAND
YYSFNKEFDE HSRAGTIERM QNGVALLMRE YGYSEEEARE ILKKEINKME QQFMDMYLTW
LNGPVQKSRG LIQYLTMVLC LYSGTMFWMA HGARYHRTDL ITTAEDRATI IGKCQGDAFR
VMEGYPPPKG LKRTASSPES APKRRASKAN NINQSNGRGG DPMVAFSGPF VKAPSHICDA
PYEYIDSLQS KNMRDKFINI LNSWLNVPSD SLQIIKNIVQ MLHNSSLMLD DIEDASPLRR
GQPATHIFYG ASQTINSANF SYVKTVIEAT HLKNPQCLQI FLEEVSDLHR GQSLDLHWRH
HGRCPTTDEY IMMVDNKTGG LFRLMARLME AESPSPITTP HLSRLLTLIG RYYQIRDDYM
NLTSADYTTK KGYCEDLDEG KFSLPLIHLL LHTSCPDRIT SALYNRVPST GLQDEVKTYI
LDAMQSARTF EYVREVLSHL HGEIMKTLDE AEKTLGINNG VRMLLVGLGL
