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 14-DEC-2022, entry version 91.
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}.
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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:0016020; C:membrane; IEA:UniProtKB-SubCell.
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 GO; GO:1901576; P:organic substance biosynthetic 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 PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 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
//