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 22-FEB-2023, entry version 92. 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; 1351063at2759; -. 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; Cytochrome P450; 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 PANTHER; PTHR46206; CYTOCHROME P450; 1. DR PANTHER; PTHR46206:SF3; P450, PUTATIVE (EUROFUNG)-RELATED; 1. 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 //