ID FTMC_NEOFI Reviewed; 548 AA.
AC A1DA60;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 27-MAR-2024, entry version 84.
DE RecName: Full=Tryprostatin B 6-hydroxylase {ECO:0000303|PubMed:23109474};
DE EC=1.14.14.118 {ECO:0000250|UniProtKB:Q4WAW5};
DE AltName: Full=Fumitremorgin biosynthesis protein C;
GN Name=ftmP450-1 {ECO:0000303|PubMed:23109474};
GN Synonyms=ftmC {ECO:0000250|UniProtKB:Q4WAW5}; ORFNames=NFIA_093700;
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:Q4WAW5,
CC ECO:0000269|PubMed:23109474}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tryprostatin B =
CC 6-hydroxytryprostatin B + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:35955, 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:72760,
CC ChEBI:CHEBI:72762; EC=1.14.14.118;
CC Evidence={ECO:0000250|UniProtKB:Q4WAW5};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:Q4WAW5}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; DS027694; EAW19750.1; -; Genomic_DNA.
DR RefSeq; XP_001261647.1; XM_001261646.1.
DR AlphaFoldDB; A1DA60; -.
DR SMR; A1DA60; -.
DR STRING; 331117.A1DA60; -.
DR EnsemblFungi; EAW19750; EAW19750; NFIA_093700.
DR GeneID; 4588680; -.
DR KEGG; nfi:NFIA_093700; -.
DR VEuPathDB; FungiDB:NFIA_093700; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_001570_14_10_1; -.
DR OMA; KRIQVYR; -.
DR OrthoDB; 2419619at2759; -.
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:1901362; P:organic cyclic compound biosynthetic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0044283; P:small molecule biosynthetic process; IEA:UniProt.
DR CDD; cd11061; CYP67-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24305; CYTOCHROME P450; 1.
DR PANTHER; PTHR24305:SF112; L-ORNITHINE-N5-MONOOXYGENASE (EUROFUNG)-RELATED; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; 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..548
FT /note="Tryprostatin B 6-hydroxylase"
FT /id="PRO_0000424120"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 491
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 548 AA; 63189 MW; 9B58E526B0622935 CRC64;
MPSVMKCGYL ATAGLIGICI HLWYFRYGEH HLYPWRYVRF HLCLTMGVSA LLYAKKPPQY
TLSPGDLVKD TCLLMVTYLI GLFTSLLLYR TLFHPLRQIR GPWAAKVSSF WLSFRLRRGP
SFRILHELHE EYGPVVRVGP SEVSIIHPEA IGIIYGPNSR CSKNAFYDNG HPMMSLHSYR
DRTAHDQRRR VWSAGFGDRA LRGYEQRMRV YRQKLFQRLE ERADAESTIN ISQWFNFYSY
DTMGDLAFAR SFDMLDASRN HWAVDMLMHG MIGYRYLFPS WFFRLLATMP SLSNDWHKFI
GFATDTMLRR LREQVGVPDI FASLLAPLNG RDPTDDERNM LMGDAMLIIT AGSDTTATSL
TSIVYELARR PDEVDKLRAE IEPIEADSDG EYQHDTLAKL PHLNGFINEA FRLHSPIPGV
IPRKTPPEGI HVKDIFIPGN MTVFSPQWSM GRSEAAYVDP AIFNPERWYK HIDLVKEKSV
FAPFSIGPYS CIGKPLAMMN IRTTVARLIM RFDVRFPEGE DGIRWMDAAD EHFAMGIHQM
PVVLTRRH
//
