AUSU_EMENI
ID AUSU_EMENI Reviewed; 148 AA.
AC A0A1U8QGE6; C8VQ91; Q5AR26;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Iron/alpha-ketoglutarate-dependent dioxygenase ausU {ECO:0000303|PubMed:29076725};
DE EC=1.14.-.- {ECO:0000305|PubMed:29076725};
DE AltName: Full=Austinoid biosynthesis clusters protein U {ECO:0000303|PubMed:29076725};
GN Name=ausU {ECO:0000303|PubMed:29076725}; ORFNames=AN9254, ANIA_09254;
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.
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.
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]
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: Iron/alpha-ketoglutarate-dependent dioxygenase; part of the
CC gene cluster B that mediates the biosynthesis of austinol and
CC dehydroaustinol, two fungal meroterpenoids (PubMed:22329759). The first
CC step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by
CC the polyketide synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic
CC acid is then prenylated by the polyprenyl transferase ausN
CC (PubMed:22329759). 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 (PubMed:22329759).
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 (PubMed:22329759, PubMed:23865690). Acid-
CC catalyzed keto-rearrangement and ring contraction of the tetraketide
CC portion of preaustinoid A3 by ausJ lead to the formation of
CC preaustinoid A4 (PubMed:22329759). The aldo-keto reductase ausK, with
CC the help of ausH, is involved in the next step by transforming
CC preaustinoid A4 into isoaustinone which is in turn hydroxylated by the
CC P450 monooxygenase ausI to form austinolide (PubMed:22329759). Finally,
CC the cytochrome P450 monooxygenase ausG modifies austinolide to austinol
CC (PubMed:22329759). Austinol can be further modified to dehydroaustinol
CC which forms a diffusible complex with diorcinol that initiates
CC conidiation (PubMed:22234162, PubMed:22329759). Due to genetic
CC rearrangements of the clusters and the subsequent loss of some enzymes,
CC the end products of the Emericella nidulans austinoid biosynthesis
CC clusters are austinol and dehydroaustinol, even if additional enzymes,
CC such as the O-acetyltransferase ausQ and the cytochrome P450
CC monooxygenase ausR are still functional (PubMed:29076725).
CC {ECO:0000269|PubMed:22234162, ECO:0000269|PubMed:22329759,
CC ECO:0000269|PubMed:23865690, ECO:0000269|PubMed:29076725}.
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q5AR53};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:29076725}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
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; CBF87254.1; -; Genomic_DNA.
DR EMBL; AACD01000172; EAA66321.1; -; Genomic_DNA.
DR RefSeq; XP_682523.1; XM_677431.1.
DR EnsemblFungi; CBF87254; CBF87254; ANIA_09254.
DR EnsemblFungi; EAA66321; EAA66321; AN9254.2.
DR GeneID; 2867771; -.
DR KEGG; ani:AN9254.2; -.
DR VEuPathDB; FungiDB:AN9254; -.
DR HOGENOM; CLU_1758786_0_0_1; -.
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: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..148
FT /note="Iron/alpha-ketoglutarate-dependent dioxygenase ausU"
FT /id="PRO_0000453863"
FT BINDING 45
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR53"
FT BINDING 47
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR53"
SQ SEQUENCE 148 AA; 16175 MW; 5C0372562099EF9E CRC64;
MTIIPKRSYN VLTTCKAVFR DVGDYWLTTG NLRTTKPQSP AQGFHRDTLL YPVLQYQPAT
SPSLIVTLLV SMTDATVANG ATRVILSSQN GRLLNTIGGP GRASRAKRWG HAGNPSAAAA
RWWEAYESGT EYKTNATNFL HKMLASCS
