ID   AUSI_PENBI              Reviewed;         500 AA.
AC   A0A0F7TSZ5;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 1.
DT   03-AUG-2022, entry version 25.
DE   RecName: Full=Cytochrome P450 monooxygenase ausI {ECO:0000303|PubMed:29076725};
DE            EC=1.-.-.- {ECO:0000305|PubMed:29076725};
DE   AltName: Full=Austinoid biosynthesis clusters protein I {ECO:0000303|PubMed:29076725};
GN   Name=ausI {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_06817;
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:Q5AR27, 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   ---------------------------------------------------------------------------
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; CDHK01000006; CEJ58147.1; -; Genomic_DNA.
DR   SMR; A0A0F7TSZ5; -.
DR   EnsemblFungi; CEJ58147; CEJ58147; PMG11_06817.
DR   OrthoDB; 614788at2759; -.
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..500
FT                   /note="Cytochrome P450 monooxygenase ausI"
FT                   /id="PRO_0000453840"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         440
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   500 AA;  56425 MW;  B20677D05F8BE82B CRC64;
     MLHETISLAL LGQPLVPGLM VVSAILYLLY STQQWRPKNL PLLNDAGPFD FLQATAVKRF
     RRDARQLIKS GFDSYNNVFA MRTDVGVELF ASPEYADQFR NHPSLKVFPF TAKMHHGHLP
     GFELCRSQPV EDRILIESVR TQLAQSLGKM IQPLASDIGQ AISDRWPSES GWQEIALGSV
     IERTIAQGTS SVYCLDEAWP EFVVKMEMAL GMASAALSAW PVMLRRVVAK FLPECLELYR
     IMDAGRELMS RDMRRRVALQ ASTGEAPLNF FEWFKEASHG EEYDELILNL RIAFASMHGL
     CDHLVKILLR LSEDPQLVDD LRKEVIQVYK THGWSKTALY HLKLMDSTFK EVQRVDPILF
     AVGRLAVADV ALKDGLIIPK GQSIRISGHT MWDEDKYPDA AHFDAYRFYK LRQAPGQENT
     AQFTSPTSDH LGFGYGGRAC PGRFFAAAVL KISLCHVLMK YDIKPANGET GPHVWEFAAA
     INANMTANVL VRRREPEIRL