ID   FTME_NEOFI              Reviewed;         526 AA.
AC   A1DA63;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 1.
DT   03-AUG-2022, entry version 68.
DE   RecName: Full=Fumitremorgin C synthase {ECO:0000303|PubMed:23109474};
DE            EC=1.14.19.71 {ECO:0000250|UniProtKB:Q4WAW8};
DE   AltName: Full=Fumitremorgin biosynthesis protein E {ECO:0000250|UniProtKB:Q4WAW8};
GN   Name=ftmP450-2 {ECO:0000303|PubMed:23109474};
GN   Synonyms=ftmE {ECO:0000250|UniProtKB:Q4WAW8}; ORFNames=NFIA_093730;
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:Q4WAW8,
CC       ECO:0000269|PubMed:23109474}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tryprostatin A =
CC         fumitremorgin C + H(+) + 2 H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:35963, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:72761,
CC         ChEBI:CHEBI:72763; EC=1.14.19.71;
CC         Evidence={ECO:0000250|UniProtKB:Q4WAW8};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:Q4WAW8}.
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; DS027694; EAW19753.1; -; Genomic_DNA.
DR   RefSeq; XP_001261650.1; XM_001261649.1.
DR   AlphaFoldDB; A1DA63; -.
DR   SMR; A1DA63; -.
DR   STRING; 36630.CADNFIAP00008713; -.
DR   EnsemblFungi; EAW19753; EAW19753; NFIA_093730.
DR   GeneID; 4588683; -.
DR   KEGG; nfi:NFIA_093730; -.
DR   VEuPathDB; FungiDB:NFIA_093730; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   HOGENOM; CLU_001570_2_1_1; -.
DR   OMA; TARLFWA; -.
DR   OrthoDB; 702827at2759; -.
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; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   SUPFAM; SSF48264; SSF48264; 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..526
FT                   /note="Fumitremorgin C synthase"
FT                   /id="PRO_0000424123"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         443
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   526 AA;  58808 MW;  55F0609CACAB3C15 CRC64;
     MERLPLSPAV LFLTITLPIL YFWILHTSPA RHHGKQLPLP PGPPRLPKIG NLHQVPRQIP
     WKKYKEWSDT YGPIMSVQLA NTIAVVFSSW DLIKTHVERR NTIYSSRPSV PFFLHATGGL
     NASILPYGPE WKLQRAIRSS VLKPSMTIKY RDVQSMETTQ LLHELLSTND FSVCLRRCIA
     SVFLTVAYGE RCADHAGLEA IDRLEELNRA IALHAEALFS GAAGILAQLV LPQALVDRLP
     VRWKKDADIL HNRLTADLVA RTRAALARPG WNWVKAFAIK EGTGSGEGDG EQGREVGLKR
     LAYMVGSLYE ASMAASQALR VIILAGILYP DATRRMHDEL DAVVGKDRLP DFNDAAQLPY
     TQAFIKEAMR WRSLTPMGSP RATSDEDECR GYHIPRGATV LVNVWAINHD EGVFLDPFTF
     KPERWIENPD LPQLLYGMGQ RACPGRHMGQ DSLFLGTARL FWAFDMALPD GAEAIDQERF
     LDSGTTLAAF LPDFEVRFTP RSEKHREVIE NSVVVSSDVS SVTVAT