EASL_ASPFU
ID EASL_ASPFU Reviewed; 436 AA.
AC Q4WZ67;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Fumigaclavine A dimethylallyltransferase easL {ECO:0000305};
DE EC=2.5.1.100 {ECO:0000269|PubMed:16397874};
DE AltName: Full=Ergot alkaloid synthesis protein L {ECO:0000303|PubMed:22453123};
GN Name=easL {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaPT1 {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G17990;
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, CATALYTIC ACTIVITY, SUBUNIT, PATHWAY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=NIH 5233 / ATCC 13073;
RX PubMed=16397874; DOI=10.1002/cbic.200500318;
RA Unsold I.A., Li S.M.;
RT "Reverse prenyltransferase in the biosynthesis of fumigaclavine C in
RT Aspergillus fumigatus: gene expression, purification, and characterization
RT of fumigaclavine C synthase FGAPT1.";
RL ChemBioChem 7:158-164(2006).
RN [5]
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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
RP IDENTIFICATION, NOMENCLATURE, AND FUNCTION.
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 [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: Fumigaclavine A dimethylallyltransferase; part of the gene
CC cluster that mediates the biosynthesis of fumiclavanine C, a fungal
CC ergot alkaloid (PubMed:15933009, PubMed:22453123). DmaW catalyzes the
CC first step of ergot alkaloid biosynthesis by condensing dimethylallyl
CC diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan
CC (PubMed:15870460). The second step is catalyzed by the
CC methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in
CC the presence of S-adenosyl-L-methionine, resulting in the formation of
CC 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the
CC FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-
CC abrine to chanoclavine-I which is further oxidized by EasD in the
CC presence of NAD(+), resulting in the formation of chanoclavine-I
CC aldehyde (PubMed:20039019, PubMed:20526482, PubMed:21409592). EasA
CC reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that
CC spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline
CC (PubMed:20526482). EasG then catalyzes the reduction of 6,8-dimethyl-
CC 6,7-didehydroergoline to form festuclavine (PubMed:20526482).
CC Hydrolysis of festuclavine by easM then leads to the formation of
CC fumigaclavine B which is in turn acetylated by easN to fumigaclavine A
CC (PubMed:26972831). Finally, easL catalyzes the conversion of
CC fumigaclavine A into fumigaclavine C by attaching a dimethylallyl
CC 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:22453123,
CC ECO:0000269|PubMed:26972831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + fumigaclavine A = diphosphate +
CC fumigaclavine C; Xref=Rhea:RHEA:34263, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57623, ChEBI:CHEBI:67145, ChEBI:CHEBI:67147;
CC EC=2.5.1.100; Evidence={ECO:0000269|PubMed:16397874};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6 uM for fumigaclavine A {ECO:0000269|PubMed:16397874};
CC KM=13 uM for dimethylallyl diphosphate {ECO:0000269|PubMed:16397874};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:16397874}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16397874}.
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 tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94098.1; -; Genomic_DNA.
DR RefSeq; XP_756136.1; XM_751043.1.
DR AlphaFoldDB; Q4WZ67; -.
DR SMR; Q4WZ67; -.
DR STRING; 746128.CADAFUBP00003301; -.
DR MEROPS; M77.002; -.
DR EnsemblFungi; EAL94098; EAL94098; AFUA_2G17990.
DR GeneID; 3512711; -.
DR KEGG; afm:AFUA_2G17990; -.
DR VEuPathDB; FungiDB:Afu2g17990; -.
DR eggNOG; ENOG502S2XP; Eukaryota.
DR HOGENOM; CLU_037431_0_0_1; -.
DR InParanoid; Q4WZ67; -.
DR OMA; LFARNHI; -.
DR OrthoDB; 1531660at2759; -.
DR BioCyc; MetaCyc:MON-15593; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IDA:AspGD.
DR GO; GO:0008233; F:peptidase activity; IDA:AspGD.
DR GO; GO:0004659; F:prenyltransferase activity; IDA:AspGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IDA:UniProtKB.
DR GO; GO:0009821; P:alkaloid biosynthetic process; IDA:AspGD.
DR GO; GO:0035837; P:ergot alkaloid biosynthetic process; IDA:UniProtKB.
DR GO; GO:1900809; P:fumigaclavine C 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; Reference proteome; Transferase.
FT CHAIN 1..436
FT /note="Fumigaclavine A dimethylallyltransferase easL"
FT /id="PRO_0000421749"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 103..104
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 112
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 126
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 211
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 281
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 285
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 357
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 422
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 426
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
SQ SEQUENCE 436 AA; 50196 MW; 9189492C1BA86F8F CRC64;
MTKTDAQGRH PQETATHAAT TDEEVQDQWR APFEVLSRTL VFQHEDHRLW WERAASKLAT
YLRLAKYSVG SQYQHLLMFY SVYAPNLGPW PNDKRDNVHW VCGICPGGEN LEISMNYQQG
AKCTVRIAAE TITPAAGTDK DPFNLTAEKK MIEDLKALQP NLNFTWFNHF QREVLVPEEV
ALNNDEIISK VPFKNQRLHG LDLSEGAFML KSYFMPAIRS AITGVENTQI MFESIRKLNL
KNANFISALS TLEDWMVPTN GRFMEYWDGI SYDAVDACKA RIKIYTGIRM KSIEHARDVW
TLGGRLQGED IEKGFDLVAR LWRRLMDEEP STCEMKYWMQ WVWELRTDVP FPVPKLYFSV
AAAEDHYVSD TVVEILDYLG WDDLVQTHRA LMDEAWSLGQ TTKSYLAFSY ISVTFHSIKG
PYITTYGNPS GPRPVF
