AUSE_EMENI
ID AUSE_EMENI Reviewed; 298 AA.
AC Q5AR34; C8VQ83;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Multifunctional dioxygenase ausE {ECO:0000303|PubMed:23865690};
DE EC=1.14.11.- {ECO:0000269|PubMed:23865690, ECO:0000269|PubMed:29317628};
DE AltName: Full=Austinoid biosynthesis clusters protein E {ECO:0000303|PubMed:22329759};
GN Name=ausE {ECO:0000303|PubMed:22329759}; ORFNames=AN9246;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION.
RX PubMed=22234162; DOI=10.1021/cb200455u;
RA Rodriguez-Urra A.B., Jimenez C., Nieto M.I., Rodriguez J., Hayashi H.,
RA Ugalde U.;
RT "Signaling the induction of sporulation involves the interaction of two
RT secondary metabolites in Aspergillus nidulans.";
RL ACS Chem. Biol. 7:599-606(2012).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22329759; DOI=10.1021/ja209809t;
RA Lo H.C., Entwistle R., Guo C.J., Ahuja M., Szewczyk E., Hung J.H.,
RA Chiang Y.M., Oakley B.R., Wang C.C.;
RT "Two separate gene clusters encode the biosynthetic pathway for the
RT meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans.";
RL J. Am. Chem. Soc. 134:4709-4720(2012).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23865690; DOI=10.1021/ja405518u;
RA Matsuda Y., Awakawa T., Wakimoto T., Abe I.;
RT "Spiro-ring formation is catalyzed by a multifunctional dioxygenase in
RT austinol biosynthesis.";
RL J. Am. Chem. Soc. 135:10962-10965(2013).
RN [6] {ECO:0007744|PDB:5YBL}
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 6-298 IN COMPLEX WITH SUBSTRATE,
RP SUBUNIT, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF LEU-150 AND SER-232, AND DOMAIN.
RX PubMed=29317628; DOI=10.1038/s41467-017-02371-w;
RA Nakashima Y., Mori T., Nakamura H., Awakawa T., Hoshino S., Senda M.,
RA Senda T., Abe I.;
RT "Structure function and engineering of multifunctional non-heme iron
RT dependent oxygenases in fungal meroterpenoid biosynthesis.";
RL Nat. Commun. 9:104-104(2018).
RN [7]
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 B that
CC mediates the biosynthesis of austinol and dehydroaustinol, two fungal
CC meroterpenoids (PubMed:22329759). The first step of the pathway is the
CC synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase
CC ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated
CC by the polyprenyl transferase ausN (PubMed:22329759). Further
CC epoxidation by the FAD-dependent monooxygenase ausM and cyclization by
CC the probable terpene cyclase ausL lead to the formation of
CC protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized
CC to spiro-lactone preaustinoid A3 by the combined action of the FAD-
CC binding monooxygenases ausB and ausC, and the dioxygenase ausE
CC (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement
CC and ring contraction of the tetraketide portion of preaustinoid A3 by
CC ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The
CC aldo-keto reductase ausK, with the help of ausH, is involved in the
CC next step by transforming preaustinoid A4 into isoaustinone which is in
CC turn hydroxylated by the P450 monooxygenase ausI to form austinolide
CC (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG
CC modifies austinolide to austinol (PubMed:22329759). Austinol can be
CC further modified to dehydroaustinol which forms a diffusible complex
CC with diorcinol that initiates conidiation (PubMed:22234162,
CC PubMed:22329759). Due to genetic rearrangements of the clusters and the
CC subsequent loss of some enzymes, the end products of the Emericella
CC nidulans austinoid biosynthesis clusters are austinol and
CC dehydroaustinol, even if additional enzymes, such as the O-
CC acetyltransferase ausQ and the cytochrome P450 monooxygenase ausR are
CC still functional (PubMed:29076725). {ECO:0000269|PubMed:22234162,
CC ECO:0000269|PubMed:22329759, ECO:0000269|PubMed:23865690,
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:0000269|PubMed:23865690, ECO:0000269|PubMed:29317628};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65133;
CC Evidence={ECO:0000269|PubMed:23865690, ECO:0000269|PubMed:29317628};
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:0000269|PubMed:23865690};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65157;
CC Evidence={ECO:0000269|PubMed:23865690};
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:0000269|PubMed:23865690};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65145;
CC Evidence={ECO:0000269|PubMed:23865690};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:29317628};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40.9 uM for preaustinoid A1 {ECO:0000269|PubMed:29317628};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:22329759, ECO:0000269|PubMed:29317628}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:29317628}.
CC -!- DOMAIN: Residues at positions 150 and 232 are important for the type of
CC reaction catalyzed, using identical substrate (PubMed:29317628). Both
CC ausE and prhA accept preaustinoid A1 as a substrate to form divergent
CC products through dynamic skeletal rearrangement (PubMed:29317628). AusE
CC (containing 'Leu-150' and 'Ser-232') first desaturates at C1-C2 to form
CC preaustinoid A2, followed by rearrangement leading to the formation of
CC the spiro-lactone in preaustinoid A3 (PubMed:29317628). In contrast,
CC prhA (containing 'Val-150' and 'Ala-232') first desaturates at C5-C6 to
CC form berkeleyone B, followed by rearrangement of the A/B-ring to form
CC the cycloheptadiene moiety in berkeleydione (PubMed:22234162).
CC {ECO:0000269|PubMed:22234162, ECO:0000269|PubMed:29317628}.
CC -!- DISRUPTION PHENOTYPE: Impairs the synthesis of austinol and
CC dehydroaustinol (PubMed:22329759). {ECO:0000269|PubMed:22329759}.
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; BN001308; CBF87240.1; -; Genomic_DNA.
DR EMBL; AACD01000172; EAA66313.1; -; Genomic_DNA.
DR RefSeq; XP_682515.1; XM_677423.1.
DR PDB; 5YBL; X-ray; 2.11 A; A/B/C/D=6-298.
DR PDBsum; 5YBL; -.
DR AlphaFoldDB; Q5AR34; -.
DR SMR; Q5AR34; -.
DR EnsemblFungi; CBF87240; CBF87240; ANIA_09246.
DR EnsemblFungi; EAA66313; EAA66313; AN9246.2.
DR GeneID; 2867933; -.
DR KEGG; ani:AN9246.2; -.
DR VEuPathDB; FungiDB:AN9246; -.
DR eggNOG; ENOG502S7ZW; Eukaryota.
DR HOGENOM; CLU_047725_1_0_1; -.
DR InParanoid; Q5AR34; -.
DR OMA; GYWMNTS; -.
DR OrthoDB; 623398at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000000560; Chromosome VIII.
DR Proteomes; UP000005890; 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:1900560; P:austinol biosynthetic process; IMP:AspGD.
DR GO; GO:1900563; P:dehydroaustinol biosynthetic process; IMP:AspGD.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..298
FT /note="Multifunctional dioxygenase ausE"
FT /id="PRO_0000436486"
FT BINDING 72
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 127
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 130
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 132
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 167
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 214
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29317628,
FT ECO:0007744|PDB:5YBL"
FT SITE 150
FT /note="Important for reaction specificity"
FT /evidence="ECO:0000269|PubMed:29317628"
FT SITE 232
FT /note="Important for reaction specificity"
FT /evidence="ECO:0000269|PubMed:29317628"
FT MUTAGEN 150
FT /note="L->V: No longer produces preaustinoid A3, but yields
FT the B-ring-expanded berkeleydione as a single product; when
FT associated with A-232."
FT /evidence="ECO:0000269|PubMed:29317628"
FT MUTAGEN 232
FT /note="S->A: Gains a prhA-type 'B-ring expansion' activity
FT to produce berkeleydione, while retaining the 'spiro-
FT lactone forming' activity to produce preaustinoid A3. No
FT longer produces preaustinoid A3, but yields the B-ring-
FT expanded berkeleydione as a single product; when associated
FT with V-150."
FT /evidence="ECO:0000269|PubMed:29317628"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:5YBL"
FT TURN 66..69
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 81..85
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 91..101
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 110..120
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 137..142
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 171..175
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 226..235
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 258..263
FT /evidence="ECO:0007829|PDB:5YBL"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:5YBL"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:5YBL"
SQ SEQUENCE 298 AA; 33254 MW; B9987CF1207532BA CRC64;
MGSATPSRLQ KFPATAPADE IYAAFKEDGC VIIEGFVPPD QMARFSQEIQ PAMEKIQVQV
TNDGNSNDRV KRFSKLVTTS PTFRHEILEN DLMHELLQRV FSKPGEGMGY HFNDTMVIEV
QPGAPAQRLH RDQELYPWWN SMGPDAPECL VNFFCAVTPF TVENGATRLV PGSNRWPELT
LINATDCPQY GKIDSVPAIM QPGDCYMMSG KVIHGAGHNA TLSDQRRALA FSTIRRELRP
VQAFPLWIPM QIATELSPRT QAMFGFRSST QHCDVDTVHF WGNDGKDIGE HLGLISSA
