EASA_CLAPU
ID EASA_CLAPU Reviewed; 380 AA.
AC Q6ZXC1; E9L2U7;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 2.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Probable inactive dehydrogenase easA {ECO:0000303|PubMed:20735127};
DE AltName: Full=Ergot alkaloid biosynthesis protein A {ECO:0000303|PubMed:20735127};
GN Name=easA {ECO:0000303|PubMed:20735127};
GN Synonyms=cpox3 {ECO:0000303|PubMed:15904941};
OS Claviceps purpurea (Ergot fungus) (Sphacelia segetum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX NCBI_TaxID=5111;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND IDENTIFICATION IN THE EAS
RP CLUSTER.
RC STRAIN=P1 / 1029/N5;
RX PubMed=15904941; DOI=10.1016/j.phytochem.2005.04.011;
RA Haarmann T., Machado C., Lubbe Y., Correia T., Schardl C.L.,
RA Panaccione D.G., Tudzynski P.;
RT "The ergot alkaloid gene cluster in Claviceps purpurea: extension of the
RT cluster sequence and intra species evolution.";
RL Phytochemistry 66:1312-1320(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
RX PubMed=20735127; DOI=10.1021/ja105785p;
RA Cheng J.Z., Coyle C.M., Panaccione D.G., O'Connor S.E.;
RT "Controlling a structural branch point in ergot alkaloid biosynthesis.";
RL J. Am. Chem. Soc. 132:12835-12837(2010).
RN [3]
RP BIOTECHNOLOGY.
RC STRAIN=P1 / 1029/N5;
RX PubMed=11778866; DOI=10.1007/s002530100801;
RA Tudzynski P., Correia T., Keller U.;
RT "Biotechnology and genetics of ergot alkaloids.";
RL Appl. Microbiol. Biotechnol. 57:593-605(2001).
RN [4]
RP FUNCTION.
RX PubMed=14700635; DOI=10.1016/j.chembiol.2003.11.013;
RA Correia T., Grammel N., Ortel I., Keller U., Tudzynski P.;
RT "Molecular cloning and analysis of the ergopeptine assembly system in the
RT ergot fungus Claviceps purpurea.";
RL Chem. Biol. 10:1281-1292(2003).
RN [5]
RP FUNCTION.
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
RX PubMed=14732265; DOI=10.1016/j.fgb.2003.10.002;
RA Wang J., Machado C., Panaccione D.G., Tsai H.-F., Schardl C.L.;
RT "The determinant step in ergot alkaloid biosynthesis by an endophyte of
RT perennial ryegrass.";
RL Fungal Genet. Biol. 41:189-198(2004).
RN [6]
RP FUNCTION.
RC STRAIN=P1 / 1029/N5;
RX PubMed=16538694; DOI=10.1002/cbic.200500487;
RA Haarmann T., Ortel I., Tudzynski P., Keller U.;
RT "Identification of the cytochrome P450 monooxygenase that bridges the
RT clavine and ergoline alkaloid pathways.";
RL ChemBioChem 7:645-652(2006).
RN [7]
RP FUNCTION.
RX PubMed=17308187; DOI=10.1128/aem.00257-07;
RA Fleetwood D.J., Scott B., Lane G.A., Tanaka A., Johnson R.D.;
RT "A complex ergovaline gene cluster in epichloe endophytes of grasses.";
RL Appl. Environ. Microbiol. 73:2571-2579(2007).
RN [8]
RP FUNCTION.
RX PubMed=17720822; DOI=10.1128/aem.01040-07;
RA Lorenz N., Wilson E.V., Machado C., Schardl C.L., Tudzynski P.;
RT "Comparison of ergot alkaloid biosynthesis gene clusters in Claviceps
RT species indicates loss of late pathway steps in evolution of C.
RT fusiformis.";
RL Appl. Environ. Microbiol. 73:7185-7191(2007).
RN [9]
RP FUNCTION.
RX PubMed=17560817; DOI=10.1016/j.fgb.2007.04.008;
RA Haarmann T., Lorenz N., Tudzynski P.;
RT "Use of a nonhomologous end joining deficient strain (Deltaku70) of the
RT ergot fungus Claviceps purpurea for identification of a nonribosomal
RT peptide synthetase gene involved in ergotamine biosynthesis.";
RL Fungal Genet. Biol. 45:35-44(2008).
RN [10]
RP FUNCTION.
RX PubMed=19139103; DOI=10.1074/jbc.m807168200;
RA Ortel I., Keller U.;
RT "Combinatorial assembly of simple and complex D-lysergic acid alkaloid
RT peptide classes in the ergot fungus Claviceps purpurea.";
RL J. Biol. Chem. 284:6650-6660(2009).
RN [11]
RP FUNCTION.
RX PubMed=20118373; DOI=10.1128/aem.00737-09;
RA Lorenz N., Olsovska J., Sulc M., Tudzynski P.;
RT "Alkaloid cluster gene ccsA of the ergot fungus Claviceps purpurea encodes
RT chanoclavine I synthase, a flavin adenine dinucleotide-containing
RT oxidoreductase mediating the transformation of N-methyl-
RT dimethylallyltryptophan to chanoclavine I.";
RL Appl. Environ. Microbiol. 76:1822-1830(2010).
RN [12]
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 [13]
RP FUNCTION.
RX PubMed=21494745; DOI=10.1039/c0ob01215g;
RA Matuschek M., Wallwey C., Xie X., Li S.M.;
RT "New insights into ergot alkaloid biosynthesis in Claviceps purpurea: an
RT agroclavine synthase EasG catalyses, via a non-enzymatic adduct with
RT reduced glutathione, the conversion of chanoclavine-I aldehyde to
RT agroclavine.";
RL Org. Biomol. Chem. 9:4328-4335(2011).
RN [14]
RP FUNCTION.
RX PubMed=24361048; DOI=10.1016/j.chembiol.2013.11.008;
RA Havemann J., Vogel D., Loll B., Keller U.;
RT "Cyclolization of D-lysergic acid alkaloid peptides.";
RL Chem. Biol. 21:146-155(2014).
CC -!- FUNCTION: Probable inactive dehydrogenase; part of the gene cluster
CC that mediates the biosynthesis of fungal ergot alkaloid
CC (PubMed:14732265, PubMed:14700635, PubMed:15904941, PubMed:17308187,
CC PubMed:17720822). DmaW catalyzes the first step of ergot alkaloid
CC biosynthesis by condensing dimethylallyl diphosphate (DMAP) and
CC tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:14732265). The
CC second step is catalyzed by the methyltransferase easF that methylates
CC 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-
CC methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By
CC similarity). The catalase easC and the FAD-dependent oxidoreductase
CC easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is
CC further oxidized by easD in the presence of NAD(+), resulting in the
CC formation of chanoclavine-I aldehyde (PubMed:20118373,
CC PubMed:21409592). Agroclavine dehydrogenase easG then mediates the
CC conversion of chanoclavine-I aldehyde to agroclavine via a non-
CC enzymatic adduct reaction: the substrate is an iminium intermediate
CC that is formed spontaneously from chanoclavine-I aldehyde in the
CC presence of glutathione (PubMed:20735127, PubMed:21494745). The
CC presence of easA is not required to complete this reaction
CC (PubMed:21494745). Further conversion of agroclavine to paspalic acid
CC is a two-step process involving oxidation of agroclavine to
CC elymoclavine and of elymoclavine to paspalic acid, the second step
CC being performed by the elymoclavine oxidase cloA (PubMed:16538694,
CC PubMed:17720822). Paspalic acid is then further converted to D-lysergic
CC acid (PubMed:15904941). Ergopeptines are assembled from D-lysergic acid
CC and three different amino acids by the D-lysergyl-peptide-synthetases
CC composed each of a monomudular and a trimodular nonribosomal peptide
CC synthetase subunit (PubMed:14700635, PubMed:15904941). LpsB and lpsC
CC encode the monomodular subunits responsible for D-lysergic acid
CC activation and incorporation into the ergopeptine backbone
CC (PubMed:14700635). LpsA1 and A2 subunits encode the trimodular
CC nonribosomal peptide synthetase assembling the tripeptide portion of
CC ergopeptines (PubMed:14700635). LpsA1 is responsible for formation of
CC the major ergopeptine, ergotamine, and lpsA2 for alpha-ergocryptine,
CC the minor ergopeptine of the total alkaloid mixture elaborated by
CC C.purpurea (PubMed:17560817, PubMed:19139103). D-lysergyl-tripeptides
CC are assembled by the nonribosomal peptide synthetases and released as
CC N-(D-lysergyl-aminoacyl)-lactams (PubMed:24361048). Cyclolization of
CC the D-lysergyl-tripeptides is performed by the Fe(2+)/2-ketoglutarate-
CC dependent dioxygenase easH which introduces a hydroxyl group into N-(D-
CC lysergyl-aminoacyl)-lactam at alpha-C of the aminoacyl residue followed
CC by spontaneous condensation with the terminal lactam carbonyl group
CC (PubMed:24361048). {ECO:0000250|UniProtKB:Q50EL0,
CC ECO:0000269|PubMed:14700635, ECO:0000269|PubMed:14732265,
CC ECO:0000269|PubMed:15904941, ECO:0000269|PubMed:16538694,
CC ECO:0000269|PubMed:17560817, ECO:0000269|PubMed:19139103,
CC ECO:0000269|PubMed:20118373, ECO:0000269|PubMed:20735127,
CC ECO:0000269|PubMed:21409592, ECO:0000269|PubMed:21494745,
CC ECO:0000269|PubMed:24361048, ECO:0000305|PubMed:17308187,
CC ECO:0000305|PubMed:17720822}.
CC -!- SIMILARITY: Belongs to the NADH:flavin oxidoreductase/NADH oxidase
CC family. {ECO:0000305}.
CC -!- CAUTION: In contrast to other members of the family, lacks the
CC conserved Tyr active site at position 176 which is replaced by a Phe
CC residue. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAG28312.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ703809; CAG28312.1; ALT_FRAME; Genomic_DNA.
DR EMBL; HM535793; ADU03230.1; -; Genomic_DNA.
DR AlphaFoldDB; Q6ZXC1; -.
DR SMR; Q6ZXC1; -.
DR VEuPathDB; FungiDB:CPUR_04084; -.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
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 3: Inferred from homology;
KW Flavoprotein; FMN.
FT CHAIN 1..380
FT /note="Probable inactive dehydrogenase easA"
FT /id="PRO_0000422559"
FT BINDING 25..27
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 60
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 102
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 171
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 174
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 223
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 299
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 324..325
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 325
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 352
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT VARIANT 81
FT /note="R -> Q (in strain: P1 / 1029/N5)"
FT VARIANT 118
FT /note="R -> Q (in strain: P1 / 1029/N5)"
FT VARIANT 123
FT /note="G -> E (in strain: P1 / 1029/N5)"
SQ SEQUENCE 380 AA; 42670 MW; DA921F4F3973AB9F CRC64;
MSTSNLFSTV PFGKNVLNHK IVLSPMTRFR ADDNGVPLSY MKTFYAQRAS VRGTLLVTDA
VAICPRTKGF PNVPGIWHKD RIAAWKEVVD EVHSKGSFIW LQLWATGRAA DLEALTSRGL
KLGSSSEVPV APGEPTPRAL DEDEIQQYIL DYVQGAKNAV HGAGFDGVEI HGANGFLIDQ
FLQSSCNRRT DQWGGSIENR SRFGLEITRG VVDAVGHDRV GMKLSPWSTF QGMGTMDDLV
PQFEHFITCL REMDIAYLHL ANSRWVEEED PSIRTHPDFH NQTFVQMWGK KRPILLAGGY
DPDSARRLVD QTYSDRNNVL VVFGRHYISN PDLPFRLRMG IALQKYNRDT FYIPCSGEGY
VDYPFCKEYL DQADEAAVAG
