EASF_ASPFU
ID EASF_ASPFU Reviewed; 339 AA.
AC Q4WZ60;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=4-dimethylallyltryptophan N-methyltransferase easF {ECO:0000305};
DE EC=2.1.1.261;
DE AltName: Full=4-dimethylallyltryptophan methyltransferase {ECO:0000305};
DE AltName: Full=Ergot alkaloid synthesis protein F {ECO:0000303|PubMed:22453123};
GN Name=easF {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaMT {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G18060;
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 [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 [2]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=15933009; DOI=10.1128/aem.71.6.3112-3118.2005;
RA Coyle C.M., Panaccione D.G.;
RT "An ergot alkaloid biosynthesis gene and clustered hypothetical genes from
RT Aspergillus fumigatus.";
RL Appl. Environ. Microbiol. 71:3112-3118(2005).
RN [3]
RP FUNCTION.
RX PubMed=15870460; DOI=10.1099/mic.0.27759-0;
RA Unsoeld I.A., Li S.-M.;
RT "Overproduction, purification and characterization of FgaPT2, a
RT dimethylallyltryptophan synthase from Aspergillus fumigatus.";
RL Microbiology 151:1499-1505(2005).
RN [4]
RP FUNCTION.
RX PubMed=19672909; DOI=10.1002/cbic.200900395;
RA Liu X., Wang L., Steffan N., Yin W.B., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the
RT acetylation of fumigaclavine B.";
RL ChemBioChem 10:2325-2328(2009).
RN [5]
RP INDUCTION.
RX PubMed=19028996; DOI=10.1128/ec.00265-08;
RA Twumasi-Boateng K., Yu Y., Chen D., Gravelat F.N., Nierman W.C.,
RA Sheppard D.C.;
RT "Transcriptional profiling identifies a role for BrlA in the response to
RT nitrogen depletion and for StuA in the regulation of secondary metabolite
RT clusters in Aspergillus fumigatus.";
RL Eukaryot. Cell 8:104-115(2009).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=19523108; DOI=10.1111/j.1364-3703.2009.00548.x;
RA Haarmann T., Rolke Y., Giesbert S., Tudzynski P.;
RT "Ergot: from witchcraft to biotechnology.";
RL Mol. Plant Pathol. 10:563-577(2009).
RN [7]
RP FUNCTION.
RX PubMed=20039019; DOI=10.1007/s00203-009-0536-1;
RA Wallwey C., Matuschek M., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of
RT chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain
RT alcohol dehydrogenase FgaDH.";
RL Arch. Microbiol. 192:127-134(2010).
RN [8]
RP FUNCTION, AND NOMENCLATURE.
RX PubMed=20526482; DOI=10.1039/c003823g;
RA Wallwey C., Matuschek M., Xie X.L., Li S.M.;
RT "Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of
RT chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS
RT in the presence of the old yellow enzyme FgaOx3.";
RL Org. Biomol. Chem. 8:3500-3508(2010).
RN [9]
RP FUNCTION.
RX PubMed=21409592; DOI=10.1007/s00294-011-0336-4;
RA Goetz K.E., Coyle C.M., Cheng J.Z., O'Connor S.E., Panaccione D.G.;
RT "Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I
RT in Aspergillus fumigatus.";
RL Curr. Genet. 57:201-211(2011).
RN [10]
RP IDENTIFICATION, AND NOMENCLATURE.
RX PubMed=22453123; DOI=10.3852/11-310;
RA Robinson S.L., Panaccione D.G.;
RT "Chemotypic and genotypic diversity in the ergot alkaloid pathway of
RT Aspergillus fumigatus.";
RL Mycologia 104:804-812(2012).
RN [11]
RP FUNCTION, AND PATHWAY.
RX PubMed=23435153; DOI=10.3390/toxins5020445;
RA Ryan K.L., Moore C.T., Panaccione D.G.;
RT "Partial reconstruction of the ergot alkaloid pathway by heterologous gene
RT expression in Aspergillus nidulans.";
RL Toxins 5:445-455(2013).
RN [12]
RP FUNCTION.
RX PubMed=26972831; DOI=10.1007/s00294-016-0591-5;
RA Bilovol Y., Panaccione D.G.;
RT "Functional analysis of the gene controlling hydroxylation of festuclavine
RT in the ergot alkaloid pathway of Neosartorya fumigata.";
RL Curr. Genet. 62:853-860(2016).
CC -!- FUNCTION: 4-dimethylallyltryptophan N-methyltransferase; part of the
CC gene cluster that mediates the biosynthesis of fumiclavanine C, a
CC fungal ergot alkaloid (PubMed:15933009, PubMed:23435153,
CC PubMed:26972831). DmaW catalyzes the first step of ergot alkaloid
CC biosynthesis by condensing dimethylallyl diphosphate (DMAP) and
CC tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:15870460). The
CC second step is catalyzed by the methyltransferase easF that methylates
CC 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-
CC methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By
CC similarity). The catalase easC and the FAD-dependent oxidoreductase
CC easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is
CC further oxidized by EasD in the presence of NAD(+), resulting in the
CC formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482,
CC PubMed:21409592). EasA reduces chanoclavine-I aldehyde to
CC dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form
CC 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then
CC catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form
CC festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then
CC leads to the formation of fumigaclavine B which is in turn acetylated
CC by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes
CC the conversion of fumigaclavine A into fumigaclavine C by attaching a
CC dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).
CC {ECO:0000250|UniProtKB:B6D5I7, ECO:0000269|PubMed:15870460,
CC ECO:0000269|PubMed:15933009, ECO:0000269|PubMed:19672909,
CC ECO:0000269|PubMed:20039019, ECO:0000269|PubMed:20526482,
CC ECO:0000269|PubMed:21409592, ECO:0000269|PubMed:23435153,
CC ECO:0000269|PubMed:26972831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-(3-methylbut-2-enyl)-L-tryptophan + S-adenosyl-L-methionine
CC = 4-(3-methylbut-2-enyl)-L-abrine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:34435, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:58209, ChEBI:CHEBI:59789, ChEBI:CHEBI:67248;
CC EC=2.1.1.261;
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:23435153}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- INDUCTION: The expression of the ergot alkaloid synthesis cluster which
CC leads to the synthesis of fumigaclavines is positively regulated by the
CC brlA and stuA transcription factors (PubMed:19028996).
CC {ECO:0000269|PubMed:19028996}.
CC -!- BIOTECHNOLOGY: Ergot alkaloids are known for their toxic effects on
CC humans who consume contaminated grains or livestock that graze on
CC grasses harboring ergot alkaloid-producing fungi (PubMed:19523108). Due
CC to their strong affinity for monoamine neurotransmitter receptors they
CC may also have clinical uses such as treatment of migraines, Parkinson's
CC disease and cerebrovascular insufficiency (PubMed:19523108).
CC {ECO:0000305|PubMed:19523108}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94105.1; -; Genomic_DNA.
DR RefSeq; XP_756143.1; XM_751050.1.
DR AlphaFoldDB; Q4WZ60; -.
DR SMR; Q4WZ60; -.
DR STRING; 746128.CADAFUBP00003308; -.
DR EnsemblFungi; EAL94105; EAL94105; AFUA_2G18060.
DR GeneID; 3512718; -.
DR KEGG; afm:AFUA_2G18060; -.
DR VEuPathDB; FungiDB:Afu2g18060; -.
DR eggNOG; ENOG502SISP; Eukaryota.
DR HOGENOM; CLU_049766_0_2_1; -.
DR InParanoid; Q4WZ60; -.
DR OMA; FGCSYKY; -.
DR OrthoDB; 762504at2759; -.
DR BRENDA; 2.1.1.261; 508.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0008168; F:methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0035837; P:ergot alkaloid biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900809; P:fumigaclavine C biosynthetic process; IDA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR019257; MeTrfase_dom.
DR InterPro; IPR017804; MeTrfase_EgtD-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR017805; SAM_MeTrfase_EasF-type_put.
DR Pfam; PF10017; Methyltransf_33; 1.
DR PIRSF; PIRSF018005; UCP018005; 1.
DR TIGRFAMs; TIGR03439; methyl_EasF; 1.
PE 2: Evidence at transcript level;
KW Alkaloid metabolism; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..339
FT /note="4-dimethylallyltryptophan N-methyltransferase easF"
FT /id="PRO_0000421752"
SQ SEQUENCE 339 AA; 38094 MW; 10841D50EF3DBBA0 CRC64;
MTISAPPIID IRQAGLESSI PDQVVEGLTK EVKTLPALLF YSTKGIQHWN RHSHAADFYP
RHEELCILKA EASKMAASIA QDSLVIDMGS ASMDKVILLL EALEEQKKSI TYYALDLSYS
ELASNFQAIP VDRFHYVRFA ALHGTFDDGL HWLQNAPDIR NRPRCILLFG LTIGNFSRDN
AASFLRNIAQ SALSTSPTQS SIIVSLDSCK LPTKILRAYT ADGVVPFALA SLSYANSLFH
PKGDRKIFNE EDWYFHSEWN HALGRHEASL ITQSKDIQLG APLETVIVRR DEKIRFGCSY
KYDKAERDQL FHSAGLEDAA VWTAPDCDVA FYQLRLRLN
