ID   IDTP_CLAPA              Reviewed;         498 AA.
AC   J7FIP8;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2012, sequence version 1.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Cytochrome P450 monooxygenase idtP {ECO:0000303|PubMed:23468653};
DE            EC=1.-.-.- {ECO:0000305|PubMed:32077051};
DE   AltName: Full=Indole-diterpene biosynthesis cluster protein P {ECO:0000303|PubMed:23468653};
DE   Flags: Precursor;
GN   Name=idtP {ECO:0000303|PubMed:23468653};
OS   Claviceps paspali (Rye ergot fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX   NCBI_TaxID=40601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, AND FUNCTION.
RC   STRAIN=RRC-1481;
RX   PubMed=23468653; DOI=10.1371/journal.pgen.1003323;
RA   Schardl C.L., Young C.A., Hesse U., Amyotte S.G., Andreeva K., Calie P.J.,
RA   Fleetwood D.J., Haws D.C., Moore N., Oeser B., Panaccione D.G.,
RA   Schweri K.K., Voisey C.R., Farman M.L., Jaromczyk J.W., Roe B.A.,
RA   O'Sullivan D.M., Scott B., Tudzynski P., An Z., Arnaoudova E.G.,
RA   Bullock C.T., Charlton N.D., Chen L., Cox M., Dinkins R.D., Florea S.,
RA   Glenn A.E., Gordon A., Gueldener U., Harris D.R., Hollin W., Jaromczyk J.,
RA   Johnson R.D., Khan A.K., Leistner E., Leuchtmann A., Li C., Liu J., Liu J.,
RA   Liu M., Mace W., Machado C., Nagabhyru P., Pan J., Schmid J., Sugawara K.,
RA   Steiner U., Takach J.E., Tanaka E., Webb J.S., Wilson E.V., Wiseman J.L.,
RA   Yoshida R., Zeng Z.;
RT   "Plant-symbiotic fungi as chemical engineers: Multi-genome analysis of the
RT   Clavicipitaceae reveals dynamics of alkaloid loci.";
RL   PLoS Genet. 9:E1003323-E1003323(2013).
RN   [2]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=29457197; DOI=10.1007/s00253-018-8807-x;
RA   Kozak L., Szilagyi Z., Vago B., Kakuk A., Toth L., Molnar I., Pocsi I.;
RT   "Inactivation of the indole-diterpene biosynthetic gene cluster of
RT   Claviceps paspali by Agrobacterium-mediated gene replacement.";
RL   Appl. Microbiol. Biotechnol. 102:3255-3266(2018).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=32077051; DOI=10.1007/s12223-020-00777-6;
RA   Kozak L., Szilagyi Z., Toth L., Pocsi I., Molnar I.;
RT   "Functional characterization of the idtF and idtP genes in the Claviceps
RT   paspali indole diterpene biosynthetic gene cluster.";
RL   Folia Microbiol. (Praha) 65:605-613(2020).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of paspalitrems, indole-diterpene (IDT)
CC       mycotoxins that are potent tremorgens in mammals (PubMed:23468653,
CC       PubMed:29457197, PubMed:32077051). The geranylgeranyl diphosphate
CC       (GGPP) synthase idtG is proposed to catalyze the first step in IDT
CC       biosynthesis via catalysis of a series of iterative condensations of
CC       isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP),
CC       geranyl diphosphate (GPP), and farnesyl diphosphate (FPP), to form GGPP
CC       (Probable). Condensation of indole-3-glycerol phosphate with GGPP by
CC       the prenyltransferase idtC then forms 3-geranylgeranylindole (3-GGI)
CC       (Probable). Epoxidation of the two terminal alkenes of the
CC       geranylgeranyl moiety by the FAD-dependent monooxygenase idtM, and
CC       cyclization by the terpene cyclase idtB then leads to the production of
CC       paspaline (Probable). The cytochrome P450 monooxygenase idtP then
CC       catalyzes oxidative elimination of the pendant methyl group at C-12 of
CC       paspaline and generates the C-10 ketone to yield 13-desoxypaxilline
CC       (PubMed:32077051). The cytochrome P450 monooxygenase idtQ may catalyze
CC       the C-13 oxidation of 13-desoxypaxilline to afford paxilline
CC       (Probable). Considering that both paspalicine and paxilline were
CC       detected in C.paspali, idtQ also catalyzes the formation of paspalinine
CC       from 13-desoxypaxilline via paspalicine as an intermediate (Probable).
CC       Finally, the alpha-prenyltransferase idtF prenylates paspalinine at the
CC       C-20 or the C-21 positions to yield paspalitrems A and C, respectively
CC       (PubMed:32077051). The hydroxylation of paspalitrem A at C-32 by a
CC       still unknown oxidase affords paspalitrem B (Probable).
CC       {ECO:0000269|PubMed:23468653, ECO:0000269|PubMed:29457197,
CC       ECO:0000269|PubMed:32077051, ECO:0000305|PubMed:29457197}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32077051, ECO:0000305|PubMed:29457197}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of all paspalitrems, but
CC       accumulates paspaline. {ECO:0000269|PubMed:32077051}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; JN613321; AFO85418.1; -; Genomic_DNA.
DR   AlphaFoldDB; J7FIP8; -.
DR   SMR; J7FIP8; -.
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   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   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..498
FT                   /note="Cytochrome P450 monooxygenase idtP"
FT                   /id="PRO_5003792117"
FT   BINDING         439
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   498 AA;  57051 MW;  C46FEEDB414C633E CRC64;
     MFLLHILAIG ACLLWYFVRS DKRKQGSNIP TIRRWPALFP EFLDRLSYNS CAARLVENGY
     REHKDRPFRL LKMDMDLVVI PLKYAQEMRA LTSDELDPLT AVFDDNVGKV TGILLDSQLH
     THAIQRRLTP RLPNIIPAMM DELNYAFQQV IPSEAGERLQ TSWVPINPYD MVLELSTRAA
     ARLFVGEPIC RDEVFLKTSA AYSRNIFDTI HVSRSLGHII TPYLGSLIPS VRQFHQQFEY
     IQNLVLGEIA HRKQHSEDNK ADDFLQWCME LARTKEESTP TALAQRTVGI LSMAVVHTSA
     MATTHLLFDM ISNQELREQL RTEQKQVLKQ GWMGITQQTM LDMKQLDSVM RESQRINPVG
     EFTFRRIVRK PITLSDGFQL HPGQQIAIAA RCINTDGDVL PDAETFKPMR WMEKESAAST
     GFAHSSDSNL HFGLGRYACP GRFLASYMIK AIISRVLFDY EFKLQDDSAA GRPPNLIHGD
     KIFPSRDVTV LFRRRHDE