ID   AUSR_EMENI              Reviewed;         535 AA.
AC   Q5AR29; C8VQ88;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 2.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=Cytochrome P450 monooxygenase ausR {ECO:0000303|PubMed:29076725};
DE            EC=1.-.-.- {ECO:0000269|PubMed:29076725};
DE   AltName: Full=Austinoid biosynthesis clusters protein R {ECO:0000303|PubMed:29076725};
GN   Name=ausR {ECO:0000303|PubMed:29076725}; ORFNames=AN9251, ANIA_09251;
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, AND CATALYTIC ACTIVITY.
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: Cytochrome P450 monooxygenase; part of the gene cluster B
CC       that mediates the biosynthesis of austinol and dehydroaustinol, two
CC       fungal meroterpenoids (PubMed:22329759). The first step of the pathway
CC       is the synthesis of 3,5-dimethylorsellinic acid by the polyketide
CC       synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then
CC       prenylated by the polyprenyl transferase ausN (PubMed:22329759).
CC       Further epoxidation by the FAD-dependent monooxygenase ausM and
CC       cyclization by the probable terpene cyclase ausL lead to the formation
CC       of protoaustinoid A (PubMed:22329759). Protoaustinoid A is then
CC       oxidized to spiro-lactone preaustinoid A3 by the combined action of the
CC       FAD-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   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:29076725}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
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 cytochrome P450 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=EAA66318.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AACD01000172; EAA66318.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BN001308; CBF87249.1; -; Genomic_DNA.
DR   RefSeq; XP_682520.1; XM_677428.1.
DR   EnsemblFungi; CBF87249; CBF87249; ANIA_09251.
DR   EnsemblFungi; EAA66318; EAA66318; AN9251.2.
DR   GeneID; 2867944; -.
DR   KEGG; ani:AN9251.2; -.
DR   VEuPathDB; FungiDB:AN9251; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   HOGENOM; CLU_022195_0_3_1; -.
DR   OMA; NYAIDAF; -.
DR   OrthoDB; 572303at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000000560; Chromosome VIII.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..535
FT                   /note="Cytochrome P450 monooxygenase ausR"
FT                   /id="PRO_0000453841"
FT   TRANSMEM        51..71
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         474
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   535 AA;  60770 MW;  B056193E8A8ACCF5 CRC64;
     MIIFNISALG PPKPMLQFVG RELVETSRAT MLRLPIDSAM HPFSTLPNHE LGLYIMWMMS
     AVFVIFKLLA PAKCDIPTVN GRRRFEIGQY QARRRFSVDG RGIILNGLQM ARVFRVVSQK
     GPKIILGPEY ANEVKSHPAC NADVFIAKEF HAHVSGFEVL RPQQVMKDAI RLRLTRSIGA
     LMKPISAETA LILESQWGNS NCWHELDLNF TIASLVSRVS AVMFVGEELG RDQKWLSIVT
     NYSSDMFVAD LDLCKWPEAL RPIATYFLPS CGKLRRHIRE AALMLYPILS EGYSAHQNKQ
     NFLDWLEEIA GDRKYNPVLA QLSLAAAAID TTSDLIIKTL TDICRFRDSQ KLQEDLREEM
     VRVLRADGWE KSAMYNLKLL DSVLKETQRV KPVVVFGMGR YVTEQITLHD GTVISKGETI
     NVVNTRIWDP AVYPNPLEWD PYRFVRRRDS GDHAAHLVSP TPDHMGFGLG KHSCPGRFFA
     ATKIKIILCH ILLKYDVKIP DEEISTVISS GNFLFPDSTL RISVRRRQDN LTIWD