FTMB_ASPFM
ID FTMB_ASPFM Reviewed; 464 AA.
AC B9WZX3;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 03-AUG-2022, entry version 41.
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};
OS Neosartorya fumigata (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=746128;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=BM939;
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 [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
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.
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 [6]
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 [7]
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).
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:23090579). The three cytochrome P450
CC monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are
CC 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
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:23090579, ECO:0000269|PubMed:23649274, ECO:0000305,
CC 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}.
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DR EMBL; AB436628; BAH23998.1; -; Genomic_DNA.
DR AlphaFoldDB; B9WZX3; -.
DR SMR; B9WZX3; -.
DR MEROPS; M77.004; -.
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 Alkaloid metabolism; Prenyltransferase; Transferase; Virulence.
FT CHAIN 1..464
FT /note="Tryprostatin B synthase"
FT /id="PRO_0000424112"
FT BINDING 94
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 102
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 113
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 201
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 203
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 205
FT /ligand="brevianamide F"
FT /ligand_id="ChEBI:CHEBI:64530"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 294
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 296
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 380
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 382
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 446
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 450
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT SITE 115
FT /note="Required for regioselectivity"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
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
