ID   ROQO_PENRW              Reviewed;         503 AA.
AC   B6HJU3;
DT   08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 77.
DE   RecName: Full=Cytochrome P450 monooxygenase roqO {ECO:0000305};
DE            EC=1.-.-.- {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953};
DE   AltName: Full=Roquefortine/meleagrin synthesis protein O {ECO:0000303|PubMed:23776469};
GN   Name=roqO {ECO:0000303|PubMed:23776469}; ORFNames=Pc21g15450;
OS   Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS   54-1255) (Penicillium chrysogenum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC   Penicillium chrysogenum species complex.
OX   NCBI_TaxID=500485;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX   PubMed=18820685; DOI=10.1038/nbt.1498;
RA   van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA   Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA   Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA   Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA   van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA   Bovenberg R.A.L.;
RT   "Genome sequencing and analysis of the filamentous fungus Penicillium
RT   chrysogenum.";
RL   Nat. Biotechnol. 26:1161-1168(2008).
RN   [2]
RP   FUNCTION.
RX   PubMed=22118684; DOI=10.1016/j.chembiol.2011.08.012;
RA   Garcia-Estrada C., Ullan R.V., Albillos S.M., Fernandez-Bodega M.A.,
RA   Durek P., von Doehren H., Martin J.F.;
RT   "A single cluster of coregulated genes encodes the biosynthesis of the
RT   mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum.";
RL   Chem. Biol. 18:1499-1512(2011).
RN   [3]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=24225953; DOI=10.1074/jbc.m113.512665;
RA   Ries M.I., Ali H., Lankhorst P.P., Hankemeier T., Bovenberg R.A.,
RA   Driessen A.J., Vreeken R.J.;
RT   "Novel key metabolites reveal further branching of the
RT   roquefortine/meleagrin biosynthetic pathway.";
RL   J. Biol. Chem. 288:37289-37295(2013).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=23776469; DOI=10.1371/journal.pone.0065328;
RA   Ali H., Ries M.I., Nijland J.G., Lankhorst P.P., Hankemeier T.,
RA   Bovenberg R.A., Vreeken R.J., Driessen A.J.;
RT   "A branched biosynthetic pathway is involved in production of roquefortine
RT   and related compounds in Penicillium chrysogenum.";
RL   PLoS ONE 8:E65328-E65328(2013).
RN   [5]
RP   BIOTECHNOLOGY.
RX   PubMed=26692349; DOI=10.1016/j.bmc.2015.11.038;
RA   Mady M.S., Mohyeldin M.M., Ebrahim H.Y., Elsayed H.E., Houssen W.E.,
RA   Haggag E.G., Soliman R.F., El Sayed K.A.;
RT   "The indole alkaloid meleagrin, from the olive tree endophytic fungus
RT   Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent
RT   breast cancer proliferation, migration and invasion.";
RL   Bioorg. Med. Chem. 24:113-122(2016).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of the mycotoxin meleagrin (PubMed:22118684,
CC       PubMed:23776469). The first stage is catalyzed by the dipeptide
CC       synthase roqA which condenses histidine and tryptophan to produce
CC       histidyltryptophanyldiketopiperazine (HTD) (PubMed:22118684,
CC       PubMed:23776469). HTD is then converted to roquefortine C through two
CC       possible pathways (PubMed:23776469). In the first pathway,
CC       prenyltransferase roqD transforms HTD to the intermediate roquefortine
CC       D, which is in turn converted to roquefortine C by the cytochrome P450
CC       monooxygenase roqR (PubMed:23776469). In the second pathway, HTD is
CC       first converted to the intermediate dehydrohistidyltryptophanyldi-
CC       ketopiperazine (DHTD) by roqR which is then prenylated by roqD to form
CC       roquefortine C (PubMed:23776469). Roquefortine C can be further
CC       transformed to meleagrin via three more reactions including oxydation
CC       to glandicolin A by roqM, which is further reduced to glandicoline B by
CC       roqO (PubMed:23776469). Finally, glandicoline B is converted to
CC       meleagrin by the glandicoline B O-methyltransferase roqN
CC       (PubMed:22118684, PubMed:23776469). More studies identified further
CC       branching and additional metabolites produced by the
CC       roquefortine/meleagrin cluster, including roquefortine F, roquefortine
CC       L, roquefortine M, roquefortine N and neoxaline (PubMed:24225953).
CC       {ECO:0000269|PubMed:22118684, ECO:0000269|PubMed:23776469,
CC       ECO:0000269|PubMed:24225953}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:22118684,
CC       ECO:0000269|PubMed:23776469, ECO:0000269|PubMed:24225953}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is decreased in presence of phenylacetic acid
CC       (PAA) (PubMed:23776469). {ECO:0000269|PubMed:23776469}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of glandicoline B and
CC       meleagrin (PubMed:23776469). {ECO:0000269|PubMed:23776469}.
CC   -!- BIOTECHNOLOGY: The indole alkaloid meleagrin was shown to be a good
CC       candidate to control c-Met-dependent breast cancer proliferation,
CC       migration and invasion (PubMed:26692349).
CC       {ECO:0000269|PubMed:26692349}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AM920436; CAP96442.1; -; Genomic_DNA.
DR   RefSeq; XP_002568555.1; XM_002568509.1.
DR   AlphaFoldDB; B6HJU3; -.
DR   SMR; B6HJU3; -.
DR   STRING; 1108849.XP_002568555.1; -.
DR   EnsemblFungi; CAP96442; CAP96442; PCH_Pc21g15450.
DR   GeneID; 8315546; -.
DR   KEGG; pcs:Pc21g15450; -.
DR   VEuPathDB; FungiDB:PCH_Pc21g15450; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   HOGENOM; CLU_022195_0_3_1; -.
DR   OMA; RICEHPE; -.
DR   OrthoDB; 614788at2759; -.
DR   BioCyc; PCHR:PC21G15450-MON; -.
DR   Proteomes; UP000000724; Contig Pc00c21.
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:0008152; P:metabolic process; IEA:UniProt.
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   1: Evidence at protein level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..503
FT                   /note="Cytochrome P450 monooxygenase roqO"
FT                   /id="PRO_0000436347"
FT   TRANSMEM        11..31
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         444
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"
FT   CARBOHYD        205
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   503 AA;  57477 MW;  CC4012842D407006 CRC64;
     MDVVARFMVS YSGTACAISL FIFGITLLFP FHKSQSFVCM NSHSWDIFRN KAKREFESNA
     EKLIKDALRK GLTAFQLVTN MGTYLILADQ YAEELRNDKR LSAYDALNDV ILLELPGLET
     MFQGSLHNHV SPTAIHAMNR ELVHLTRALS DEANHRLQTQ WTDSSEWHTV SIHDTVLALV
     AQMTTRAFVG AELCRNAEWL DIAINFTINR AIAVQAVQAW PWILQPVVHW FLPTCKAVRR
     QIQRARTILM PVLERERQTM HRKDSSSDRI FSTLTFIDQY AQGSRYDATM AQLRLTAVSV
     LTTSDMVEKV LARICEHPEL IQPLREEVVS VFESSGLHHK SLLKLTLMES VMKESQRLEP
     ATLISMFRAA KKTVTLQDGT TIPKGTRLAF ANDLRLDPEL YPDPETFDGY RFERMRKDPE
     QAKLAPFTKT RTSHLAFGHG KHACPGRFLS CDEAKLILCH ILLKYDFKAL DGRVPDLHVR
     SMFIQRDTGG MLSVRRRQEE VTL