FTMH_ASPFM
ID FTMH_ASPFM Reviewed; 427 AA.
AC B9WZX7; D3TIT5;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=12-alpha,13-alpha-dihydroxyfumitremorgin C prenyltransferase {ECO:0000303|PubMed:18683158};
DE EC=2.5.1.110 {ECO:0000269|PubMed:18683158};
DE AltName: Full=Fumitremorgin biosynthesis protein H {ECO:0000303|PubMed:23649274};
GN Name=ftmPT2 {ECO:0000303|PubMed:18683158};
GN Synonyms=ftmH {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 NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC STRAIN=NIH 5233 / ATCC 13073;
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 [3]
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 [4]
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 [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=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 [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).
CC -!- FUNCTION: 12-alpha,13-alpha-dihydroxyfumitremorgin C prenyltransferase;
CC part of the gene cluster that mediates the biosynthesis of
CC fumitremorgins, indole alkaloids that carry not only intriguing
CC chemical structures, but also interesting biological and
CC pharmacological activities (PubMed:18683158, PubMed:23649274). 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 ftmA
CC (PubMed:16755625). Brevianamide F is then prenylated by the
CC 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=12alpha,13alpha-dihydroxyfumitremorgin C + dimethylallyl
CC diphosphate = diphosphate + fumitremorgin B; Xref=Rhea:RHEA:35971,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:64531,
CC ChEBI:CHEBI:72764; EC=2.5.1.110;
CC Evidence={ECO:0000269|PubMed:18683158};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:18683158,
CC ECO:0000269|PubMed:23649274}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {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; AB436628; BAH24002.1; -; Genomic_DNA.
DR EMBL; EU622826; ACF22981.1; -; mRNA.
DR AlphaFoldDB; B9WZX7; -.
DR SMR; B9WZX7; -.
DR BioCyc; MetaCyc:MON-18768; -.
DR BRENDA; 2.5.1.110; 508.
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..427
FT /note="12-alpha,13-alpha-dihydroxyfumitremorgin C
FT prenyltransferase"
FT /id="PRO_0000424114"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 105
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 192
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 268
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 353
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 355
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 419
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT BINDING 423
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q4WAW7"
FT CONFLICT 165
FT /note="R -> K (in Ref. 2; ACF22981)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="P -> A (in Ref. 2; ACF22981)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 427 AA; 48584 MW; 26F23D63CE60F100 CRC64;
MTIPTEISCP EEDAFQLLDK FSWFPSDDQR RWWEYTGPYL LKLLRDAKYP QKDQVPCLYL
LQQLLVPYLG TFPVVGQAPL PWWSNVTTYG VPFELSWNLL HNIVRIGFEP LSHLAESGVD
AFNKTAPEEC VSRLACLDNT IDLARFRHFQ HHLLVTPEEE TWLLREKAPL PKSGRGQQTL
AVEFQNGGIS AKAYFFPGMK SLATGLSPGK LILDSIERLA LPGLKEPVHH LRSTLGLQDD
GHPTDTAIAP FLLGVDLCTP ERSRLKFYVT DQVVSWDRVA DMWTLRGKRL EDPQCADGLA
LLRKLWDLLA IPEGYRSNIR PDFAFGTPPP EDYRPVMMAN WTLSPKKKFP DPQIYLLTVG
MNDAVVMDAL VAFYEVLGWT DLASTYKDKV ASYFPGPDFT KTNYIHSGVS FSYRHSKPYL
SVYYSPF
