FTMF_ASPFM
ID FTMF_ASPFM Reviewed; 291 AA.
AC B9WZX5;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 25-MAY-2022, entry version 38.
DE RecName: Full=Verruculogen synthase {ECO:0000303|PubMed:19763315};
DE EC=1.14.11.38 {ECO:0000269|PubMed:19763315};
DE AltName: Full=Fumitremorgin biosynthesis protein F {ECO:0000303|PubMed:23649274};
GN Name=ftmOx1 {ECO:0000303|PubMed:19763315};
GN Synonyms=ftmF {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.
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, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND PATHWAY.
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: Verruculogen synthase; part of the gene cluster that mediates
CC the biosynthesis of fumitremorgins, indole alkaloids that carry not
CC only intriguing chemical structures, but also interesting biological
CC and pharmacological activities (PubMed:19763315, 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=2-oxoglutarate + AH2 + fumitremorgin B + 2 O2 = A + CO2 + H2O
CC + succinate + verruculogen; Xref=Rhea:RHEA:35975, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:17499, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:64531, ChEBI:CHEBI:72765; EC=1.14.11.38;
CC Evidence={ECO:0000269|PubMed:19763315};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:19763315};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:19763315,
CC ECO:0000269|PubMed:23649274}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19763315}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; AB436628; BAH24000.1; -; Genomic_DNA.
DR AlphaFoldDB; B9WZX5; -.
DR SMR; B9WZX5; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Dioxygenase; Iron; Oxidoreductase; Virulence.
FT CHAIN 1..291
FT /note="Verruculogen synthase"
FT /id="PRO_0000424134"
FT ACT_SITE 68
FT /evidence="ECO:0000250|UniProtKB:Q4WAW9"
SQ SEQUENCE 291 AA; 32695 MW; 80A14F7C87DAFB24 CRC64;
MTVDSKPQLQ RLAADADVDR MCRLLEEDGA FILKGLLPFD VVESFNRELD VQMAIPPPKG
ERLLADKYPP HFKYVPNVAT TCPTFRNTIL INPVIHAICE AYFQRTGDYW LSAAFLREIE
SGMPAQPFHR DDATHPLMHY QPLEAPPISL SVIFPLTEFT EENGATEVIL GSHRWTEVGT
PERDQAVLAT MDPGDVLIVR QRVVHAGGGN RTTAGKPRRV VLAYFNSVQL TPFETYRTMP
REMVESMTVL GQRMLGWRTM KPSDPNIVGI NLIDDKRLEN VLQLKAADSP A
