EASA_ASPFU
ID EASA_ASPFU Reviewed; 376 AA.
AC Q4WZ70;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Chanoclavine-I aldehyde reductase easA {ECO:0000305};
DE EC=1.3.1.100 {ECO:0000269|PubMed:20526482};
DE AltName: Full=Ergot alkaloid synthesis protein A {ECO:0000303|PubMed:22453123};
DE AltName: Full=Old yellow enzyme 3 homolog {ECO:0000303|PubMed:21898587};
GN Name=easA {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaOx3 {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G17960;
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, CATALYTIC ACTIVITY, PATHWAY, AND NOMENCLATURE.
RC STRAIN=NIH 5233 / ATCC 13073;
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 FUNCTION.
RC STRAIN=NIH 5233 / ATCC 13073;
RX PubMed=21898587; DOI=10.1002/mrc.2796;
RA Xie X., Wallwey C., Matuschek M., Steinbach K., Li S.M.;
RT "Formyl migration product of chanoclavine-I aldehyde in the presence of the
RT old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure
RT elucidation.";
RL Magn. Reson. Chem. 49:678-681(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).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH FMN.
RX PubMed=25286934; DOI=10.1107/s2053230x14018962;
RA Chilton A.S., Ellis A.L., Lamb A.L.;
RT "Structure of an Aspergillus fumigatus old yellow enzyme (EasA) involved in
RT ergot alkaloid biosynthesis.";
RL Acta Crystallogr. F Struct. Biol. Commun. 70:1328-1332(2014).
CC -!- FUNCTION: Aldehyde reductase; part of the gene cluster that mediates
CC the biosynthesis of fumiclavanine C, a fungal ergot alkaloid
CC (PubMed:15933009, PubMed:22453123). DmaW catalyzes the first step of
CC ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate
CC (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:19672909, ECO:0000269|PubMed:20039019,
CC ECO:0000269|PubMed:20526482, ECO:0000269|PubMed:21409592,
CC ECO:0000269|PubMed:21898587, ECO:0000269|PubMed:22453123,
CC ECO:0000269|PubMed:26972831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrochanoclavine-I aldehyde + NADP(+) = chanoclavine-I
CC aldehyde + H(+) + NADPH; Xref=Rhea:RHEA:35947, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:65032,
CC ChEBI:CHEBI:71487; EC=1.3.1.100;
CC Evidence={ECO:0000269|PubMed:20526482};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:25286934};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:20526482}.
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 NADH:flavin oxidoreductase/NADH oxidase
CC family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94095.1; -; Genomic_DNA.
DR RefSeq; XP_756133.1; XM_751040.1.
DR PDB; 4QNW; X-ray; 1.80 A; A=1-376.
DR PDBsum; 4QNW; -.
DR AlphaFoldDB; Q4WZ70; -.
DR SMR; Q4WZ70; -.
DR STRING; 746128.CADAFUBP00003298; -.
DR EnsemblFungi; EAL94095; EAL94095; AFUA_2G17960.
DR GeneID; 3512708; -.
DR KEGG; afm:AFUA_2G17960; -.
DR VEuPathDB; FungiDB:Afu2g17960; -.
DR eggNOG; KOG0134; Eukaryota.
DR HOGENOM; CLU_012153_0_0_1; -.
DR InParanoid; Q4WZ70; -.
DR OMA; YDVIIAF; -.
DR OrthoDB; 978998at2759; -.
DR BioCyc; MetaCyc:MON-17452; -.
DR BRENDA; 1.3.1.100; 508.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0003959; F:NADPH dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016646; F:oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor; TAS:UniProtKB.
DR GO; GO:0035837; P:ergot alkaloid biosynthetic process; IDA:UniProtKB.
DR GO; GO:1900809; P:fumigaclavine C biosynthetic process; IDA:GO_Central.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001155; OxRdtase_FMN_N.
DR InterPro; IPR045247; Oye-like.
DR PANTHER; PTHR22893; PTHR22893; 1.
DR Pfam; PF00724; Oxidored_FMN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Flavoprotein; FMN; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..376
FT /note="Chanoclavine-I aldehyde reductase easA"
FT /id="PRO_0000421753"
FT ACT_SITE 178
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 29..31
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 64
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 106
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 173
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 225
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 297
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 323..324
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25286934"
FT BINDING 324
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 351
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 19..27
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4QNW"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 83..98
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:4QNW"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 145..164
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 179..184
FT /evidence="ECO:0007829|PDB:4QNW"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 204..217
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 241..255
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 280..286
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 300..312
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 318..323
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 324..328
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 332..338
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:4QNW"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:4QNW"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:4QNW"
FT HELIX 366..370
FT /evidence="ECO:0007829|PDB:4QNW"
SQ SEQUENCE 376 AA; 42186 MW; 24C1C309856CC7A0 CRC64;
MREEPSSAQL FKPLKVGRCH LQHRMIMAPT TRFRADGQGV PLPFVQEYYG QRASVPGTLL
ITEATDITPK AMGYKHVPGI WSEPQREAWR EIVSRVHSKK CFIFCQLWAT GRAADPDVLA
DMKDLISSSA VPVEEKGPLP RALTEDEIQQ CIADFAQAAR NAINAGFDGV EIHGANGYLI
DQFTQKSCNH RQDRWGGSIE NRARFAVEVT RAVIEAVGAD RVGVKLSPYS QYLGMGTMDE
LVPQFEYLIA QMRRLDVAYL HLANSRWLDE EKPHPDPNHE VFVRVWGQSS PILLAGGYDA
ASAEKVTEQM AAATYTNVAI AFGRYFISTP DLPFRVMAGI QLQKYDRASF YSTLSREGYL
DYPFSAEYMA LHNFPV
