ID   AUSR_PENBI              Reviewed;         496 AA.
AC   A0A0F7TN11;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 1.
DT   03-AUG-2022, entry version 24.
DE   RecName: Full=Cytochrome P450 monooxygenase ausR {ECO:0000303|PubMed:29076725};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29076725};
DE   AltName: Full=Austinoid biosynthesis clusters protein R {ECO:0000303|PubMed:29076725};
GN   Name=ausR {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_06813;
OS   Penicillium brasilianum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=104259;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MG11;
RX   PubMed=26337871; DOI=10.1128/genomea.00724-15;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Brakhage A.A.,
RA   Valiante V.;
RT   "Draft genome sequence of the fungus Penicillium brasilianum MG11.";
RL   Genome Announc. 3:0-0(2015).
RN   [2]
RP   FUNCTION.
RX   PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA   Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA   Zhang H., Hayashi F., Abe I.;
RT   "Discovery of key dioxygenases that diverged the paraherquonin and
RT   acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL   J. Am. Chem. Soc. 138:12671-12677(2016).
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: Cytochrome P450 monooxygenase; part of the gene cluster B
CC       that mediates the biosynthesis of the fungal meroterpenoid
CC       acetoxydehydroaustin (PubMed:29076725). The first step of the pathway
CC       is the synthesis of 3,5-dimethylorsellinic acid by the polyketide
CC       synthase ausA (By similarity). 3,5-dimethylorsellinic acid is then
CC       prenylated by the polyprenyl transferase ausN (By similarity). 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 (By similarity). Protoaustinoid A is then oxidized to
CC       spiro-lactone preaustinoid A3 by the combined action of the FAD-binding
CC       monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity).
CC       Acid-catalyzed keto-rearrangement and ring contraction of the
CC       tetraketide portion of preaustinoid A3 by ausJ lead to the formation of
CC       preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the
CC       help of ausH, is involved in the next step by transforming preaustinoid
CC       A4 into isoaustinone which is in turn hydroxylated by the P450
CC       monooxygenase ausI to form austinolide (By similarity). The cytochrome
CC       P450 monooxygenase ausG then modifies austinolide to austinol (By
CC       similarity). Austinol is further acetylated to austin by the O-
CC       acetyltransferase ausP, which spontaneously changes to dehydroaustin
CC       (PubMed:29076725). The cytochrome P450 monooxygenase then converts
CC       dehydroaustin is into 7-dehydrodehydroaustin (PubMed:29076725). The
CC       hydroxylation catalyzed by ausR permits the second O-acetyltransferase
CC       ausQ to add an additional acetyl group to the molecule, leading to the
CC       formation of acetoxydehydroaustin (PubMed:29076725). Due to genetic
CC       rearrangements of the clusters and the subsequent loss of some enzymes,
CC       the end product of the Penicillium brasilianum austinoid biosynthesis
CC       clusters is acetoxydehydroaustin (PubMed:29076725).
CC       {ECO:0000250|UniProtKB:Q5AR29, 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}.
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DR   EMBL; CDHK01000006; CEJ58143.1; -; Genomic_DNA.
DR   SMR; A0A0F7TN11; -.
DR   EnsemblFungi; CEJ58143; CEJ58143; PMG11_06813.
DR   OrthoDB; 572303at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000042958; 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: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.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..496
FT                   /note="Cytochrome P450 monooxygenase ausR"
FT                   /id="PRO_0000453843"
FT   TRANSMEM        12..32
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         435
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   496 AA;  56255 MW;  D1A82BC730A48EAA CRC64;
     MHSFSTLPNH RIGLYILWTI PVLFVIFKLL APAKCSLPIV NGRRWFEIGQ YQARRRFSLD
     GRGIILKGLQ KARAFRVVSQ KGPKIILGPE YANEVKSHPA CNADVFIAKE FHAHVSGFEV
     LRPQHVMKDA IRLKLTRSIG ALMRPISDET TLILETQWGN SNCWHELDLK STIAALVSRV
     SAVMFVGEEL GRDQKWLSIV TNYSSDMFVA DLDLCKWPEI LRPIATYFLS SCGKLRRHIQ
     EAALMLDPIL SEGNSTHGNK QNFLDWFEEI AGGRKYNPVL AQISLAAAAI DTTSDLIIQT
     LTDICRFPDS EKLQEELREE MVRVLRADGW EKSAMYNLKL LDSVLKETQR VKPVVVFGMG
     RYVTEQITLH DGTVIPKGET INVVNTRVWD SAVYENPLEW DPYRFLRRRD SGDHAAHLVS
     PTPDHMGFGL GKHSCPGRFF AATKIKILLC HILLKYDVKI SDEASSKVVS SGNFLFPDAT
     LRISVRRRQE NLSIWD