FTMB_ASPFU
ID FTMB_ASPFU Reviewed; 464 AA.
AC Q4WAW7; Q4G2I1;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Tryprostatin B synthase {ECO:0000303|PubMed:16000710};
DE EC=2.5.1.106 {ECO:0000269|PubMed:16000710};
DE AltName: Full=Brevianamide F prenyltransferase {ECO:0000303|PubMed:16000710};
DE AltName: Full=Fumitremorgin biosynthesis protein B {ECO:0000303|PubMed:23649274};
GN Name=ftmPT1 {ECO:0000303|PubMed:16000710};
GN Synonyms=ftmB {ECO:0000303|PubMed:23649274}; ORFNames=AFUA_8G00210;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
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 [2]
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 [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.
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=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 [8]
RP FUNCTION, AND PATHWAY.
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH DIMETHYLALLYL
RP S-THIOLODIPHOSPHATE AND BREVIANAMIDE F, AND MUTAGENESIS OF GLU-102; GLY-115
RP AND HIS-279.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
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).
CC -!- FUNCTION: Brevianamide F prenyltransferase; part of the gene cluster
CC that mediates the biosynthesis of fumitremorgins, indole alkaloids that
CC carry not only intriguing chemical structures, but also interesting
CC biological and pharmacological activities (PubMed:16000710,
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=brevianamide F + dimethylallyl diphosphate = diphosphate +
CC tryprostatin B; Xref=Rhea:RHEA:35939, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57623, ChEBI:CHEBI:64530, ChEBI:CHEBI:72760;
CC EC=2.5.1.106; Evidence={ECO:0000269|PubMed:16000710};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=55 uM for brevianamide F {ECO:0000269|PubMed:16000710};
CC KM=74 uM for dimethylallyl diphosphate {ECO:0000269|PubMed:16000710};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:16000710,
CC ECO:0000269|PubMed:23649274}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL85145.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AY861687; AAX56314.1; -; mRNA.
DR EMBL; AAHF01000014; EAL85145.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_747183.1; XM_742090.1.
DR PDB; 3O24; X-ray; 2.50 A; A=1-464.
DR PDB; 3O2K; X-ray; 2.40 A; A=1-464.
DR PDBsum; 3O24; -.
DR PDBsum; 3O2K; -.
DR AlphaFoldDB; Q4WAW7; -.
DR SMR; Q4WAW7; -.
DR STRING; 746128.CADAFUBP00008411; -.
DR ChEMBL; CHEMBL5635; -.
DR MEROPS; M77.004; -.
DR GeneID; 3504530; -.
DR KEGG; afm:AFUA_8G00210; -.
DR eggNOG; ENOG502S2XP; Eukaryota.
DR HOGENOM; CLU_037431_0_0_1; -.
DR InParanoid; Q4WAW7; -.
DR OrthoDB; 1531660at2759; -.
DR BioCyc; MetaCyc:MON-18762; -.
DR BRENDA; 2.5.1.106; 508.
DR PRO; PR:Q4WAW7; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
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 3D-structure; Prenyltransferase; Reference proteome; Transferase;
KW Virulence.
FT CHAIN 1..464
FT /note="Tryprostatin B synthase"
FT /id="PRO_0000424111"
FT BINDING 94
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 102
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 113
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 201
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 203
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 205
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 294
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 296
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 380
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 382
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 446
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT BINDING 450
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000269|PubMed:21105662"
FT SITE 115
FT /note="Required for regioselectivity"
FT /evidence="ECO:0000269|PubMed:21105662"
FT MUTAGEN 102
FT /note="E->Q: Abolishes tryprostatin B synthase activity."
FT /evidence="ECO:0000269|PubMed:21105662"
FT MUTAGEN 115
FT /note="G->T: Retains ability to consume brevianamide F but
FT mediates formation of a different product that carries a
FT reverse prenyl moiety at the C-3 of the indole nucleus."
FT /evidence="ECO:0000269|PubMed:21105662"
FT MUTAGEN 279
FT /note="H->F: Slightly affects tryprostatin B synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:21105662"
FT CONFLICT 415
FT /note="G -> A (in Ref. 1; AAX56314)"
FT /evidence="ECO:0000305"
FT HELIX 17..23
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 31..50
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:3O2K"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:3O2K"
FT TURN 107..110
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:3O24"
FT HELIX 134..145
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 152..161
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 165..173
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 207..213
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 235..249
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 293..303
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 304..311
FT /evidence="ECO:0007829|PDB:3O2K"
FT TURN 312..316
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 320..335
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 363..369
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:3O24"
FT STRAND 378..384
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 390..403
FT /evidence="ECO:0007829|PDB:3O2K"
FT HELIX 407..419
FT /evidence="ECO:0007829|PDB:3O2K"
FT TURN 426..428
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 432..441
FT /evidence="ECO:0007829|PDB:3O2K"
FT STRAND 444..451
FT /evidence="ECO:0007829|PDB:3O2K"
SQ SEQUENCE 464 AA; 52607 MW; 75B775A0420B6D5B CRC64;
MPPAPPDQKP CHQLQPAPYR ALSESILFGS VDEERWWHST APILSRLLIS SNYDVDVQYK
YLSLYRHLVL PALGPYPQRD PETGIIATQW RSGMVLTGLP IEFSNNVARA LIRIGVDPVT
ADSGTAQDPF NTTRPKVYLE TAARLLPGVD LTRFYEFETE LVITKAEEAV LQANPDLFRS
PWKSQILTAM DLQKSGTVLV KAYFYPQPKS AVTGRSTEDL LVNAIRKVDR EGRFETQLAN
LQRYIERRRR GLHVPGVTAD KPPATAADKA FDACSFFPHF LSTDLVEPGK SRVKFYASER
HVNLQMVEDI WTFGGLRRDP DALRGLELLR HFWADIQMRE GYYTMPRGFC ELGKSSAGFE
APMMFHFHLD GSQSPFPDPQ MYVCVFGMNS RKLVEGLTTF YRRVGWEEMA SHYQGNFLAN
YPDEDFEKAA HLCAYVSFAY KNGGAYVTLY NHSFNPVGDV SFPN
