EASD_ASPFU
ID EASD_ASPFU Reviewed; 261 AA.
AC Q4WZ66;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Chanoclavine-I dehydrogenase easD {ECO:0000303|PubMed:20039019};
DE Short=ChaDH {ECO:0000303|PubMed:20039019};
DE EC=1.1.1.332 {ECO:0000269|PubMed:20039019};
DE AltName: Full=Ergot alkaloid synthesis protein A {ECO:0000303|PubMed:22453123};
GN Name=easD {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaDH {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G18000;
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
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.
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: Chanoclavine-I dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid
CC (PubMed:15933009, PubMed:26972831). 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:15933009, ECO:0000269|PubMed:19672909,
CC ECO:0000269|PubMed:20039019, ECO:0000269|PubMed:20526482,
CC ECO:0000269|PubMed:21409592, ECO:0000269|PubMed:26972831}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chanoclavine-I + NAD(+) = chanoclavine-I aldehyde + H(+) +
CC NADH; Xref=Rhea:RHEA:33891, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:71487, ChEBI:CHEBI:72949;
CC EC=1.1.1.332; Evidence={ECO:0000269|PubMed:20039019};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.27 mM for Chanoclavine-I {ECO:0000269|PubMed:20039019};
CC KM=1.1 mM for NAD(+) {ECO:0000269|PubMed:20039019};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:20039019}.
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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94099.1; -; Genomic_DNA.
DR RefSeq; XP_756137.1; XM_751044.1.
DR AlphaFoldDB; Q4WZ66; -.
DR SMR; Q4WZ66; -.
DR STRING; 746128.CADAFUBP00003302; -.
DR EnsemblFungi; EAL94099; EAL94099; AFUA_2G18000.
DR GeneID; 3512712; -.
DR KEGG; afm:AFUA_2G18000; -.
DR VEuPathDB; FungiDB:Afu2g18000; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_1_0_1; -.
DR InParanoid; Q4WZ66; -.
DR OMA; MATHYGI; -.
DR OrthoDB; 1226147at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:AspGD.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; ISS:UniProtKB.
DR GO; GO:0009820; P:alkaloid metabolic process; IDA:AspGD.
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:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..261
FT /note="Chanoclavine-I dehydrogenase easD"
FT /id="PRO_0000421747"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
FT BINDING 16..40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q12634"
SQ SEQUENCE 261 AA; 27796 MW; 4D8824EB115CA636 CRC64;
MASVESRIIA ITGGASGIGA ATCRLLAERG AAVLCVCDIS PKNFDDLKIS IKKINPSTKV
HCATVDVTSS VEVRQWIEGI ISDFGDLHGA VNAAGIAQGA GMRNTPTIAE EVDEEWTRIM
NTNLNGVFYC TREEVRAMKG LPATDRSIVN VGSIASVSHM PDVYAYGTSK GACAYFTTCV
AADAFPLGIR INNVSPGVTN TPMLPQFAPM AKTFEEIEES YKKEGLSLIE AEDVARTIVW
LLSEDSRPVF GANINVGACM P
