ID   JANP_PENJA              Reviewed;         515 AA.
AC   A0A0E3D8P0;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   03-AUG-2022, entry version 17.
DE   RecName: Full=Cytochrome P450 monooxygenase janP {ECO:0000303|PubMed:26213965};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26213965};
DE   AltName: Full=Janthitremanes biosynthesis cluster protein P {ECO:0000303|PubMed:26213965};
GN   Name=janP {ECO:0000303|PubMed:26213965};
OS   Penicillium janthinellum (Penicillium vitale).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5079;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, DISRUPTION
RP   PHENOTYPE, AND PATHWAY.
RC   STRAIN=PN2408;
RX   PubMed=26213965; DOI=10.3390/toxins7082701;
RA   Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT   "Molecular cloning and functional analysis of gene clusters for the
RT   biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT   janthinellum.";
RL   Toxins 7:2701-2722(2015).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of the indole diterpenes janthitremanes such
CC       as shearinine K or shearinine A (PubMed:26213965). The geranylgeranyl
CC       diphosphate (GGPP) synthase janG catalyzes the first step in
CC       janthitremane biosynthesis via conversion of farnesyl pyrophosphate and
CC       isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP)
CC       (PubMed:26213965). Condensation of indole-3-glycerol phosphate with
CC       GGPP by the prenyl transferase janC then forms 3-geranylgeranylindole
CC       (3-GGI) (PubMed:26213965). Epoxidation by the FAD-dependent
CC       monooxygenase janM leads to a epoxidized-GGI that is substrate of the
CC       terpene cyclase janB for cyclization to yield paspaline
CC       (PubMed:26213965). Paspaline is subsequently converted to 13-
CC       desoxypaspaline by the cytochrome P450 monooxygenase janP, via beta-PC-
CC       M6 in a series of alpha-face oxidations (Probable). The cytochrome P450
CC       monooxygenase janQ is proposed to carry out sequential beta-face
CC       oxidation steps at C-7 and C-13 of 13-desoxypaspaline to form
CC       paspalicine and paspalinine respectively (Probable). The indole
CC       diterpene prenyltransferase janD may then convert paspalinine into
CC       shearinine K which is substrate of janO and/or additional enzymes for
CC       oxidation and cyclization to generate shearinine A (Probable).
CC       {ECO:0000269|PubMed:26213965, ECO:0000305|PubMed:26213965}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:26213965}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of the janthitremanes
CC       shearinine A, F or K as well as of 13-desoxypaxilline.
CC       {ECO:0000269|PubMed:26213965}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; KF280651; AGZ20476.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0E3D8P0; -.
DR   SMR; A0A0E3D8P0; -.
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; 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   3: Inferred from homology;
KW   Glycoprotein; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..515
FT                   /note="Cytochrome P450 monooxygenase janP"
FT                   /id="PRO_0000446571"
FT   TRANSMEM        20..36
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         456
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        501
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   515 AA;  58664 MW;  4364113A3E1EFE0A CRC64;
     MSALIIQLSR VVGTLREEAG FLWKYAAFMV FIYLLLPKPA YKTNVRVPTI KFMSPWLPGI
     ISRLLFNSKA PSVIYDGYSK YKTSAYKLLK PDGDLVVLST RYAEELRQLP ASTLNALEAT
     FSDHVGEYTT ILTDSHLHTE TIQKRLTPAI GRLIPRIISE LDYAFQVEFP NCDNQFVAIN
     SYEVFLRLVA RVGARIFIGD ELCREEKWLK ASIDYTKNIF LTIALLRPFP GFLHPIVGRI
     LPSSRSLDRQ LVYIKEELLG PLINKRRSLE AVSDSNYEKP DDFLQWMMDL AKTEKESHPH
     NLAQRLLGIT SMAVVHTSAM SMTHILYDLL VMPQWVQPLR DEIQTEIADW RSTTQSNLNN
     LRVMDSFLKE SQRFNPPGEL SFHRVVKHDL TLSDGLLLPK GTHICMAAGP ISMDPEVVEN
     PDVFDAFRFV KEKVPTSGFV STGPSHMHFG LGRYACPGRF FASIVMKLIL SRFLAQYEFH
     FAPDQTERPR NLLIGDKIVP NVSTPIFIKN RAPEI