ID   FTMG_NEOFI              Reviewed;         504 AA.
AC   A1DA65;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 1.
DT   03-AUG-2022, entry version 90.
DE   RecName: Full=Fumitremorgin C monooxygenase {ECO:0000303|PubMed:23109474};
DE            EC=1.14.14.119 {ECO:0000250|UniProtKB:Q4WAX0};
DE   AltName: Full=Fumitremorgin biosynthesis protein G {ECO:0000250|UniProtKB:Q4WAX0};
GN   Name=ftmP450-3 {ECO:0000303|PubMed:23109474};
GN   Synonyms=ftmG {ECO:0000250|UniProtKB:Q4WAX0}; ORFNames=NFIA_093750;
OS   Neosartorya fischeri (strain ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164
OS   / JCM 1740 / NRRL 181 / WB 181) (Aspergillus fischerianus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=331117;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164 / JCM 1740 / NRRL 181
RC   / WB 181;
RX   PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA   Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA   Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA   Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA   Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA   Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA   White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA   Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT   "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT   fumigatus.";
RL   PLoS Genet. 4:E1000046-E1000046(2008).
RN   [2]
RP   FUNCTION.
RX   PubMed=23109474; DOI=10.1002/cbic.201200523;
RA   Mundt K., Wollinsky B., Ruan H.L., Zhu T., Li S.M.;
RT   "Identification of the verruculogen prenyltransferase FtmPT3 by a
RT   combination of chemical, bioinformatic and biochemical approaches.";
RL   ChemBioChem 13:2583-2592(2012).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of fumitremorgins, indole alkaloids that
CC       carry not only intriguing chemical structures, but also interesting
CC       biological and pharmacological activities (PubMed:23109474). The
CC       biosynthesis of fumitremorgin-type alkaloids begins by condensation of
CC       the two amino acids L-tryptophan and L-proline to brevianamide F,
CC       catalyzed by the non-ribosomal peptide synthetase ftmPS/ftmA (By
CC       similarity). Brevianamide F is then prenylated by the prenyltransferase
CC       ftmPT1/ftmB in the presence of dimethylallyl diphosphate, resulting in
CC       the formation of tryprostatin B (By similarity). The three cytochrome
CC       P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG,
CC       are responsible for the conversion of tryprostatin B to 6-
CC       hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC       fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively (By
CC       similarity). The putative methyltransferase ftmMT/ftmD is expected for
CC       the conversion of 6-hydroxytryprostatin B to tryprostatin A (By
CC       similarity). FtmPT2/FtmH catalyzes the prenylation of 12,13-
CC       dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate,
CC       resulting in the formation of fumitremorgin B (By similarity).
CC       Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via
CC       the insertion of an endoperoxide bond between the two prenyl moieties
CC       (By similarity). Finally, verruculogen is further converted to
CC       fumitremorgin A by the verruculogen prenyltransferase ftmPT3
CC       (PubMed:23109474). {ECO:0000250|UniProtKB:Q4WAX0,
CC       ECO:0000269|PubMed:23109474}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=fumitremorgin C + 2 O2 + 2 reduced [NADPH--hemoprotein
CC         reductase] = 12alpha,13alpha-dihydroxyfumitremorgin C + 2 H(+) + 2
CC         H2O + 2 oxidized [NADPH--hemoprotein reductase];
CC         Xref=Rhea:RHEA:35967, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:72763,
CC         ChEBI:CHEBI:72764; EC=1.14.14.119;
CC         Evidence={ECO:0000250|UniProtKB:Q4WAX0};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:Q4WAX0}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
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; DS027694; EAW19755.1; -; Genomic_DNA.
DR   RefSeq; XP_001261652.1; XM_001261651.1.
DR   AlphaFoldDB; A1DA65; -.
DR   SMR; A1DA65; -.
DR   STRING; 36630.CADNFIAP00008576; -.
DR   EnsemblFungi; EAW19755; EAW19755; NFIA_093750.
DR   GeneID; 4588685; -.
DR   KEGG; nfi:NFIA_093750; -.
DR   VEuPathDB; FungiDB:NFIA_093750; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   HOGENOM; CLU_022195_0_3_1; -.
DR   OMA; RICEHPE; -.
DR   OrthoDB; 614788at2759; -.
DR   Proteomes; UP000006702; 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:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
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   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Alkaloid metabolism; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW   Virulence.
FT   CHAIN           1..504
FT                   /note="Fumitremorgin C monooxygenase"
FT                   /id="PRO_0000424126"
FT   TRANSMEM        9..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         442
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   504 AA;  57231 MW;  8797F1A7339B8999 CRC64;
     METFDAIQLP YPGVVGASLL VILGIILLFP LDTGHFISIN QHPWDFFQTK AKQEFEYNAA
     ALLNEGLQTG RSAFRLVTNM VTYLILKDQY AEEIKNDSRF GAHEAVDPVL LVDLPGLETM
     FQGSLHNQVP PMAVRALNKE LVHLTPFLSE EAMNCLQTRW TDSAEWHDVS IPETVLALIA
     QMTTRALLGP ALCRNPEWLD IAKSFTTNRA IAVAAVQSWP SFLQPVIHWF LSPCRALRRQ
     IQCARNILLP VLERERRSYR SDQPTKREFS NLAFIDQYAK GARYDATMAQ LRIIAVAFQT
     TSDLVEKVIA RLCKHPELIQ PLREEVVSVV GKNGLHSHSL RKLTLMESVM KETQRLEPAV
     IIGMFRLAKE KVTLKDGTVI PKGTNIAFAN DLRFDPEMYP EPETFDGYRF QRMREDPEKI
     DLTPFTKTRM SHLAFGHGKH ACPGRFLACD EAKLILCHIL LKYEIRAVEG SPPELRARGM
     FVQLDPGAMM SVRRRRENEF ALHG