FTME_ASPFU
ID FTME_ASPFU Reviewed; 526 AA.
AC Q4WAW8;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Fumitremorgin C synthase {ECO:0000303|PubMed:19226505};
DE EC=1.14.19.71 {ECO:0000269|PubMed:19226505};
DE AltName: Full=Cytochrome P450 monooxygenase ftmP450-2 {ECO:0000303|PubMed:19226505};
DE AltName: Full=Fumitremorgin biosynthesis protein E {ECO:0000303|PubMed:23649274};
GN Name=ftmP450-2 {ECO:0000303|PubMed:19226505};
GN Synonyms=ftmE {ECO:0000303|PubMed:23649274}; ORFNames=AFUA_8G00220;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=16000710; DOI=10.1099/mic.0.27962-0;
RA Grundmann A., Li S.M.;
RT "Overproduction, purification and characterization of FtmPT1, a
RT brevianamide F prenyltransferase from Aspergillus fumigatus.";
RL Microbiology 151:2199-2207(2005).
RN [3]
RP FUNCTION.
RX PubMed=16755625; DOI=10.1002/cbic.200600003;
RA Maiya S., Grundmann A., Li S.M., Turner G.;
RT "The fumitremorgin gene cluster of Aspergillus fumigatus: identification of
RT a gene encoding brevianamide F synthetase.";
RL ChemBioChem 7:1062-1069(2006).
RN [4]
RP FUNCTION.
RX PubMed=18683158; DOI=10.1002/cbic.200800240;
RA Grundmann A., Kuznetsova T., Afiyatullov S.S., Li S.M.;
RT "FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the
RT last step in the biosynthesis of fumitremorgin B.";
RL ChemBioChem 9:2059-2063(2008).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19226505; DOI=10.1002/cbic.200800787;
RA Kato N., Suzuki H., Takagi H., Asami Y., Kakeya H., Uramoto M., Usui T.,
RA Takahashi S., Sugimoto Y., Osada H.;
RT "Identification of cytochrome P450s required for fumitremorgin biosynthesis
RT in Aspergillus fumigatus.";
RL ChemBioChem 10:920-928(2009).
RN [6]
RP FUNCTION.
RX PubMed=19763315; DOI=10.1039/b908392h;
RA Steffan N., Grundmann A., Afiyatullov S., Ruan H., Li S.M.;
RT "FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase,
RT catalyses the endoperoxide formation of verruculogen in Aspergillus
RT fumigatus.";
RL Org. Biomol. Chem. 7:4082-4087(2009).
RN [7]
RP FUNCTION.
RX PubMed=21105662; DOI=10.1021/ja106817c;
RA Jost M., Zocher G., Tarcz S., Matuschek M., Xie X., Li S.M., Stehle T.;
RT "Structure-function analysis of an enzymatic prenyl transfer reaction
RT identifies a reaction chamber with modifiable specificity.";
RL J. Am. Chem. Soc. 132:17849-17858(2010).
RN [8]
RP FUNCTION.
RX PubMed=23090579; DOI=10.1039/c2ob26149a;
RA Wollinsky B., Ludwig L., Xie X., Li S.M.;
RT "Breaking the regioselectivity of indole prenyltransferases: identification
RT of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of
RT the regular C2-prenyltransferase FtmPT1.";
RL Org. Biomol. Chem. 10:9262-9270(2012).
RN [9]
RP FUNCTION, AND PATHWAY.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=23649274; DOI=10.1271/bbb.130026;
RA Kato N., Suzuki H., Okumura H., Takahashi S., Osada H.;
RT "A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in
RT Aspergillus fumigatus strain Af293.";
RL Biosci. Biotechnol. Biochem. 77:1061-1067(2013).
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:19226505,
CC PubMed:23649274). The biosynthesis of fumitremorgin-type alkaloids
CC begins by condensation of the two amino acids L-tryptophan and L-
CC proline to brevianamide F, catalyzed by the non-ribosomal peptide
CC synthetase ftmA (PubMed:16755625). Brevianamide F is then prenylated by
CC the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl
CC diphosphate, resulting in the formation of tryprostatin B
CC (PubMed:16000710, PubMed:21105662, PubMed:23090579). The three
CC cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and
CC ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to
CC 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively
CC (PubMed:19226505). The putative methyltransferase ftmMT/ftmD is
CC expected for the conversion of 6-hydroxytryprostatin B to tryprostatin
CC A (Probable). 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 (PubMed:18683158).
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 (PubMed:19763315). In some fungal species, verruculogen is further
CC converted to fumitremorgin A, but the enzymes involved in this step
CC have not been identified yet (Probable). {ECO:0000269|PubMed:16000710,
CC ECO:0000269|PubMed:16755625, ECO:0000269|PubMed:18683158,
CC ECO:0000269|PubMed:19226505, ECO:0000269|PubMed:19763315,
CC ECO:0000269|PubMed:21105662, ECO:0000269|PubMed:23090579,
CC ECO:0000269|PubMed:23649274, ECO:0000305, ECO:0000305|PubMed:16000710}.
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:0000269|PubMed:19226505};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:19226505,
CC ECO:0000269|PubMed:23649274}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: In contrast to other A.fumigatus strains, strain ATCC MYA-4609
CC does not produce indole alkaloids such as fumitremorgins and
CC verruculogen. While the biosynthetic pathway is complete, a variation
CC in the O-methyltransferase FtmD (AC Q4WAW6) abolishes production of the
CC tryprostatin A intermediate (PubMed:23649274).
CC {ECO:0000305|PubMed:23649274}.
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DR EMBL; AAHF01000014; EAL85144.1; -; Genomic_DNA.
DR RefSeq; XP_747182.1; XM_742089.1.
DR AlphaFoldDB; Q4WAW8; -.
DR SMR; Q4WAW8; -.
DR STRING; 746128.CADAFUBP00008410; -.
DR EnsemblFungi; EAL85144; EAL85144; AFUA_8G00220.
DR GeneID; 3504529; -.
DR KEGG; afm:AFUA_8G00220; -.
DR VEuPathDB; FungiDB:Afu8g00220; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_2_3_1; -.
DR InParanoid; Q4WAW8; -.
DR OMA; TARLFWA; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IBA:GO_Central.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
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 PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..526
FT /note="Fumitremorgin C synthase"
FT /id="PRO_0000424121"
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; 58983 MW; A9D616753BDA4B46 CRC64;
MERLPLSPAV LFLIIVLPIL YLWIRYTAPA RPHGKHLSLP PGPPRLPKIG NLHQVPRQIP
WKKYKEWSDT YGPIMSVQLA DTIAVVFSSW DLIKNHIERR NTIYSSRPSV PFFLHATGGL
NASILPYGPE WKLQRAIRSS VLKPSMTVKY RDVQHVETTQ LLHELLSTND FPVCLRRCIA
SVFLTVAYGE RCVDHAGLEA IDRLEELNRA IALHAEALFS GAAGILTQLV LPKALVDRLP
VRWKKDADML HNRLTADLVA RTRAALVRPG WNWVKEFSMK DGIGSGDGDG EQGSKVELKR
LAYMVGSLYE ASMAASQALR VIILAGLLHP DATRRMHDEL DAVVGTGRLP DFHDAAQLPY
TQAFIKEAMR WRSLTPMGSP RATSDEDECR GYHIPCGATV LVNVWAINHD EAIFLDPFAF
QPERWIENPD LPQLMYGMGQ RACPGRHMGQ DSLFLATARL FWAFDMALPD GADPIDQERF
LDSGTTLAAF LPDFEVRFTP RSEKYQEVIE NSMAVLPDVL SISATP
