ID   ICCF_TALVA              Reviewed;         536 AA.
AC   A0A482NAL3;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Cytochrome P450 monooxygenase iccF {ECO:0000303|PubMed:30905148};
DE            EC=1.-.-.- {ECO:0000269|PubMed:30905148};
DE   AltName: Full=Ilicicolin H biosynthesis cluster protein F {ECO:0000303|PubMed:30905148};
GN   Name=iccF {ECO:0000303|PubMed:30905148};
OS   Talaromyces variabilis (Penicillium variabile).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX   NCBI_TaxID=28576;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=HXQ-H-1;
RX   PubMed=30905148; DOI=10.1021/jacs.9b02204;
RA   Zhang Z., Jamieson C.S., Zhao Y.L., Li D., Ohashi M., Houk K.N., Tang Y.;
RT   "Enzyme-catalyzed inverse-electron demand Diels-Alder reaction in the
RT   biosynthesis of antifungal ilicicolin H.";
RL   J. Am. Chem. Soc. 141:5659-5663(2019).
CC   -!- FUNCTION: NADH-dependent flavin oxidoreductase; part of the gene
CC       cluster that mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-
CC       pyridonealkaloid that has potent and broad antifungal activities by
CC       inhibiting the mitochondrial respiration chain (PubMed:30905148). IccA
CC       to iccE are sufficient for ilicicolin H biosynthesis and the roles of
CC       the remaining enzymes, iccF, iccG and iccH within the pathway have
CC       still to be determined (PubMed:30905148). The biosynthesis of
CC       ilicicolin H starts with formation of the tetramic acid by the hybrid
CC       PKS-NRPS synthetase iccA with the partnering trans-enoyl reductase iccB
CC       since iccA lacks a designated enoylreductase (ER) domain. The
CC       cytochrome P450 monooxygenase iccC then catalyzes the ring expansion of
CC       the tetramate to the acyclic 2-pyridone. The pericyclase iccD further
CC       converts the acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the
CC       epimerase iccE converts 8-epi-ilicicolin H into ilicicolin H via
CC       epimerizationd (PubMed:30905148) (Probable).
CC       {ECO:0000269|PubMed:30905148, ECO:0000305|PubMed:30905148}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:30905148}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MK539848; QBQ83709.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A482NAL3; -.
DR   SMR; A0A482NAL3; -.
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   3: Inferred from homology;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..536
FT                   /note="Cytochrome P450 monooxygenase iccF"
FT                   /id="PRO_0000449003"
FT   TRANSMEM        17..37
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         476
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        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        321
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        387
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   536 AA;  61157 MW;  906C61BC8FA4D7D5 CRC64;
     MAPLATYLSQ IDDYPKWALF TGGSIVLFFL YRIFLSPPSY PPGVPLIAEP AGRTWFSPKT
     RWRYYTDCAS LYLEAYNQYS KKGKPVVVPG FGLGYELIMP ESLMSWVMAQ PDSAISVNQA
     FLDINKTKYS LGHTRYWGDT WQFVLVKTQL NSVLQYLIPG LNDELKLAFD AHFGTDTENW
     KEIELEKVLK NVIAQAASRF IVGAPLCRNE KYLKANYGVI EGMMLNAIFT NSSPKWLQPI
     IGPLVSKKSI NNCEIVKKEF EPLFRERLET LKHDKDDPNF EEPQDHLQLL LRYAVKERKD
     ELNDLDIIAK RIIAVNFASM NQTTMTVVNM LLNILGSDAE FNTIAVLRDE MKRTTSDGEP
     WTKAKLATMI RTDSVVRETL RINPFGNRSL MRKVIKEGLV TPDGMKLPKN SLFSFFSEPV
     QHDPDKFEDP FKYDPFRTSR EREAAADEEG KPGGHALTVV STSPNYLPWG HGKHACPGRF
     LVDCEMKMLL TYVLSNYDIE FPVEYNGQRP PTIWLAEVGL PPRGAKIRVK RRKEAI