EASE_ASPFU
ID EASE_ASPFU Reviewed; 628 AA.
AC Q4WZ61;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 84.
DE RecName: Full=FAD-linked oxidoreductase easE {ECO:0000305};
DE EC=1.-.-.- {ECO:0000305};
DE AltName: Full=Ergot alkaloid synthesis protein E {ECO:0000303|PubMed:22453123};
DE Flags: Precursor;
GN Name=easE {ECO:0000303|PubMed:22453123}; ORFNames=AFUA_2G18050;
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.
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: FAD binding oxidoreductase; part of the gene cluster that
CC mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid
CC (PubMed:15933009, PubMed:23435153, PubMed:26972831). 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,
CC PubMed:23435153). 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:23435153}.
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 oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94104.1; -; Genomic_DNA.
DR RefSeq; XP_756142.1; XM_751049.1.
DR AlphaFoldDB; Q4WZ61; -.
DR SMR; Q4WZ61; -.
DR STRING; 746128.CADAFUBP00003307; -.
DR EnsemblFungi; EAL94104; EAL94104; AFUA_2G18050.
DR GeneID; 3512717; -.
DR KEGG; afm:AFUA_2G18050; -.
DR VEuPathDB; FungiDB:Afu2g18050; -.
DR eggNOG; ENOG502R8I5; Eukaryota.
DR HOGENOM; CLU_018354_4_4_1; -.
DR InParanoid; Q4WZ61; -.
DR OMA; CHQGRIP; -.
DR OrthoDB; 827142at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:1900566; P:chanoclavine-I biosynthetic process; IMP:AspGD.
DR GO; GO:1900809; P:fumigaclavine C biosynthetic process; IDA:GO_Central.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW Alkaloid metabolism; FAD; Flavoprotein; Glycoprotein; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..628
FT /note="FAD-linked oxidoreductase easE"
FT /evidence="ECO:0000255"
FT /id="PRO_5004246710"
FT DOMAIN 144..328
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT MOD_RES 182
FT /note="Pros-8alpha-FAD histidine"
FT /evidence="ECO:0000250|UniProtKB:P08159"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 487
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 628 AA; 69384 MW; 0EF2715C2E0ECB00 CRC64;
MSHRILCVAF CVCSLVAVSS IYSPPFNHPI VYSNNAICFQ LSTWRIPQLY LAVLIRRFDL
SLSTRGVMLA VTVGVGSSQH HSQRSGLSLT FAMTPSMITL LVKTCVISQR TAVGEPHRPG
WVWEVGRTED ETCHAHSPRG APCHQGRIPL YSAAVESVDQ IQVAVRFAQR HRLRLVVRNT
GHDTAGRSSG SDSFQIHCHR MKQIEYHDNF RALGSDIDRG PAVSVGAGVT LGEMYARGAR
DGWVVVGGEC PTVGAAGGFL QGGGVSSFHS FIDGLAVDNV LEFEVVTAKG DVVVANDHQN
PDIFWALRGG GGGTFGIVTR ATMRVHLNSP VCVSEVAVSG LRNNSLLWTK GITGLFSILR
SFNQQGIPGQ FILRPLSKDQ VNASLTLYSL NTDDTRRSAE NMLSIRNILE STTLPFTLAS
RCLPKISDAL RKGPDMLPVN YGIITGSVLV SEDLFNSEEG PLHLAKQLEH FPMGPMDLLF
TSNLGGNVSA NTGKKHRDTS MHPGWRQAAH LINFVRSVST PTAHEKARSL EELHSVQMRQ
LYDIEPDFRV SYRNLGDPLE SDAAQVYWGP NYKRLLEIKR KWDPEDLFFS QLGVGSEGWT
EDQMCKRQQR LQQMLQYLMS SIAQRVYR
