EASG_ASPFU
ID EASG_ASPFU Reviewed; 290 AA.
AC Q4WZ69;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Festuclavine dehydrogenase easG {ECO:0000305};
DE EC=1.5.1.44 {ECO:0000269|PubMed:20526482};
DE AltName: Full=Ergot alkaloid biosynthetic protein G {ECO:0000303|PubMed:22453123};
GN Name=easG {ECO:0000303|PubMed:22453123};
GN Synonyms=fgaFS {ECO:0000303|PubMed:20526482}; ORFNames=AFUA_2G17970;
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 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 [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: Festuclavine dehydrogenase; part of the gene cluster that
CC mediates 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: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=festuclavine + NAD(+) = 6,8-dimethyl-6,7-didehydroergoline +
CC H(+) + NADH; Xref=Rhea:RHEA:34055, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:65034,
CC ChEBI:CHEBI:65045; EC=1.5.1.44;
CC Evidence={ECO:0000269|PubMed:20526482};
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 fgaFS/easG family. {ECO:0000305}.
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DR EMBL; AAHF01000001; EAL94096.1; -; Genomic_DNA.
DR RefSeq; XP_756134.1; XM_751041.1.
DR AlphaFoldDB; Q4WZ69; -.
DR SMR; Q4WZ69; -.
DR STRING; 746128.CADAFUBP00003299; -.
DR EnsemblFungi; EAL94096; EAL94096; AFUA_2G17970.
DR GeneID; 3512709; -.
DR KEGG; afm:AFUA_2G17970; -.
DR VEuPathDB; FungiDB:Afu2g17970; -.
DR eggNOG; ENOG502RYYU; Eukaryota.
DR HOGENOM; CLU_007383_10_6_1; -.
DR InParanoid; Q4WZ69; -.
DR OMA; WFMQNFS; -.
DR OrthoDB; 993213at2759; -.
DR BioCyc; MetaCyc:MON-17451; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000002530; Chromosome 2.
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: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 InterPro; IPR019901; Ergot_alkaloid_biosynthesis.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR03649; ergot_EASG; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..290
FT /note="Festuclavine dehydrogenase easG"
FT /id="PRO_0000421732"
SQ SEQUENCE 290 AA; 32109 MW; 6AC6B1909FB36D6C CRC64;
MTILVLGGRG KTASRLSLLL DNAGVPFLVG SSSTSYVGPY KMTHFDWLNE DTWTNVFLRA
SLDGIDPISA VYLVGGHAPE LVDPGIRFIN VARAQGVNRF VLLSASNIAK GTHSMGILHA
HLDSLEDVQY VVLRPTWFME NLLEDPHVSW IKKEDKIYSA TGDGKIPFIS ADDIARVAFS
VLTEWKSQRA QEYFVLGPEL LSYDQVADIL TTVLGRKITH VSLAEADLAR LLRDDVGLPP
DFAAMLASME TDVKHGTEVR NSHDVKKVTG SLPCSFLDFA EQEKARWMRH
