FTMT3_NEOFI
ID FTMT3_NEOFI Reviewed; 453 AA.
AC A1DJ20;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Verruculogen prenyltransferase {ECO:0000303|PubMed:23109474};
DE EC=2.5.1.107 {ECO:0000269|PubMed:23109474};
GN Name=ftmPT3 {ECO:0000303|PubMed:23109474}; ORFNames=NFIA_093400;
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
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: Verruculogen prenyltransferase; 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:Q4WAW3,
CC ECO:0000269|PubMed:23109474}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + verruculogen = diphosphate +
CC fumitremorgin A; Xref=Rhea:RHEA:35979, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57623, ChEBI:CHEBI:72765, ChEBI:CHEBI:72766;
CC EC=2.5.1.107; Evidence={ECO:0000269|PubMed:23109474};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=61.5 uM for dimethylallyl diphosphate
CC {ECO:0000269|PubMed:23109474};
CC KM=5.7 uM for verruculogen {ECO:0000269|PubMed:23109474};
CC Note=kcat is 0.069 sec(-1). {ECO:0000269|PubMed:23109474};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23109474}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; DS027696; EAW19377.1; -; Genomic_DNA.
DR RefSeq; XP_001261274.1; XM_001261273.1.
DR AlphaFoldDB; A1DJ20; -.
DR SMR; A1DJ20; -.
DR STRING; 36630.CADNFIAP00007252; -.
DR EnsemblFungi; EAW19377; EAW19377; NFIA_093400.
DR GeneID; 4587832; -.
DR KEGG; nfi:NFIA_093400; -.
DR VEuPathDB; FungiDB:NFIA_093400; -.
DR eggNOG; ENOG502RHNQ; Eukaryota.
DR HOGENOM; CLU_037431_0_0_1; -.
DR OMA; PYTTVYY; -.
DR OrthoDB; 1531660at2759; -.
DR BioCyc; MetaCyc:MON-18772; -.
DR BRENDA; 2.5.1.107; 504.
DR Proteomes; UP000006702; Unassembled WGS sequence.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR012148; DMATS-type_fun.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR PIRSF; PIRSF000509; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Prenyltransferase; Reference proteome; Transferase;
KW Virulence.
FT CHAIN 1..453
FT /note="Verruculogen prenyltransferase"
FT /id="PRO_0000424117"
FT BINDING 89
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 102
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 194
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 196
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 273
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 275
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 378
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 443
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 447
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT SITE 104
FT /note="Required for regioselectivity"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
SQ SEQUENCE 453 AA; 51628 MW; 70B6F6A64265823C CRC64;
MTIHPQNHDL PTGSAMKATP FEALDLVFHF EDQAQRQWWK QAGPVLGQHL LLANYDINKQ
YQYLCFFGHH IIPILGPGPG SGYDYHPLEI SQNFQRSGST IRLGFQPRAY SSCVSPQDPF
GELSTEEAMA RLGQVTGVEL DLQPYHLLAS HLNLTKKEEK EMLQPTCYNS LSPSFKTQGL
LAVELPRTGS ITLKGYWFLS AKSMVTKTPI SELSFQAFRN IDHGKDLLVP ALRPIEEYFA
EMKMKPANPT TPQTTEFATV ACDHVDMSRT RFKLYLYECL WKYDRLADIY TLGGRLKNAP
GIAEGLELLR EIWSILQIPE GYHFASLQNS LLRKSTNAES CGEASKPASE EREFFDDQAL
IFNFEIRPGE KWPQPKVYFP LAYLTDSKAA DAVVALFEKL GWKEEARRYK DNLKTYYPRC
DLDKTSGLQH VLSFSYRPKT GPYTTVYYWK IGA
