AUSE_ASPCI
ID AUSE_ASPCI Reviewed; 298 AA.
AC A0A0U5GHG9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=Multifunctional dioxygenase ausE {ECO:0000303|PubMed:28233494};
DE EC=1.14.11.- {ECO:0000305|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein E {ECO:0000303|PubMed:28233494};
GN Name=ausE {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14354;
OS Aspergillus calidoustus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=454130;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SF006504;
RX PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT "Draft genome sequences of fungus Aspergillus calidoustus.";
RL Genome Announc. 4:0-0(2016).
RN [2]
RP FUNCTION, AND PATHWAY.
RX PubMed=28233494; DOI=10.1021/acschembio.7b00003;
RA Valiante V., Mattern D.J., Schueffler A., Horn F., Walther G.,
RA Scherlach K., Petzke L., Dickhaut J., Guthke R., Hertweck C., Nett M.,
RA Thines E., Brakhage A.A.;
RT "Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus
RT calidoustus.";
RL ACS Chem. Biol. 12:1227-1234(2017).
RN [3]
RP FUNCTION.
RX PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL ACS Chem. Biol. 12:2927-2933(2017).
CC -!- FUNCTION: Multifunctional dioxygenase; part of the gene cluster that
CC mediates the biosynthesis of calidodehydroaustin, a fungal
CC meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the
CC pathway is the synthesis of 3,5-dimethylorsellinic acid by the
CC polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid
CC is then prenylated by the polyprenyl transferase ausN
CC (PubMed:28233494). Further epoxidation by the FAD-dependent
CC monooxygenase ausM and cyclization by the probable terpene cyclase ausL
CC lead to the formation of protoaustinoid A (By similarity).
CC Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by
CC the combined action of the FAD-binding monooxygenases ausB and ausC,
CC and the dioxygenase ausE (By similarity). Acid-catalyzed keto-
CC rearrangement and ring contraction of the tetraketide portion of
CC preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By
CC similarity). The aldo-keto reductase ausK, with the help of ausH, is
CC involved in the next step by transforming preaustinoid A4 into
CC isoaustinone which is in turn hydroxylated by the P450 monooxygenase
CC ausI to form austinolide (By similarity). The cytochrome P450
CC monooxygenase ausG modifies austinolide to austinol (By similarity).
CC Austinol is further acetylated to austin by the O-acetyltransferase
CC ausP, which spontaneously changes to dehydroaustin (PubMed:28233494).
CC The cytochrome P450 monooxygenase ausR then converts dehydroaustin is
CC into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation
CC catalyzed by ausR permits the O-acetyltransferase ausQ to add an
CC additional acetyl group to the molecule, leading to the formation of
CC acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase
CC ausT catalyzes the reduction of the double bond present between carbon
CC atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-
CC hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an
CC acetylation reaction but also the addition of the PKS ausV diketide
CC product to 1,2-dihydro-7-hydroxydehydroaustin, forming
CC precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-
CC ketoglutarate-dependent dioxygenase converts precalidodehydroaustin
CC into calidodehydroaustin (PubMed:28233494).
CC {ECO:0000250|UniProtKB:Q5AR34, ECO:0000269|PubMed:28233494,
CC ECO:0000269|PubMed:29076725}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + preaustinoid A1 = CO2 + H2O +
CC preaustinoid A2 + succinate; Xref=Rhea:RHEA:65132, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:69026, ChEBI:CHEBI:156343;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65133;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + preaustinoid A2 = CO2 + H2O +
CC preaustinoid A3 + succinate; Xref=Rhea:RHEA:65156, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:156343, ChEBI:CHEBI:156346;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65157;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + berkeleyone A + O2 = CO2 + H2O + preaustinoid
CC A + succinate; Xref=Rhea:RHEA:65144, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:69023, ChEBI:CHEBI:69024;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65145;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q5AR34};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:28233494}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q5AR34}.
CC -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC are split in their respective genomes. Genetic rearrangements provoked
CC variability among the clusters and E.nidulans produces the least number
CC of austionoid derivatives with the end products austinol and
CC dehydroaustinol, while P.brasilianum can produce until
CC acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC identified derivatives. {ECO:0000305|PubMed:29076725}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; CDMC01000024; CEL11251.1; -; Genomic_DNA.
DR SMR; A0A0U5GHG9; -.
DR EnsemblFungi; CEL11251; CEL11251; ASPCAL14354.
DR OrthoDB; 623398at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase 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 InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 3: Inferred from homology;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..298
FT /note="Multifunctional dioxygenase ausE"
FT /id="PRO_0000453852"
FT BINDING 72
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 127
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 130
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 132
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 214
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT SITE 150
FT /note="Important for reaction specificity"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
FT SITE 232
FT /note="Important for reaction specificity"
FT /evidence="ECO:0000250|UniProtKB:Q5AR34"
SQ SEQUENCE 298 AA; 33231 MW; 928E9FE35B09C2A4 CRC64;
MGSATPPRLQ KFPATAPADD IYAAFKQDGC VIIEGFVPPD QMARFSQEIQ PAMEKIQVQV
TNDGNSNDRV KRFSKLVTTS PTFRHEILEN DLMHELLQRV FSKPGEGLGY HFNDTMVIEV
QPGAPAQRLH RDQELYPWWN SMGPNAPECL VNFFCAVTPF TAENGATRLV PGSNRWPELT
LINAAECPQY GNIESAPAIM QPGDCYMMSG KVIHGAGHNA TLSDQRRALA FSTIRRELRP
VQAFPLWIPM KIARELSPRT QAMFGFRSST QHCDVDTVHF WGNDGKDIGE HLGLMSSA
