EASG_CLAP2
ID EASG_CLAP2 Reviewed; 290 AA.
AC M1WEN5; G8GV67; Q5G5T7;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 25-MAY-2022, entry version 29.
DE RecName: Full=Agroclavine dehydrogenase {ECO:0000303|PubMed:21494745};
DE EC=1.5.1.46 {ECO:0000269|PubMed:21494745};
DE AltName: Full=Ergot alkaloid biosynthesis protein G {ECO:0000303|PubMed:21494745};
GN Name=easG {ECO:0000303|PubMed:21494745};
GN Synonyms=orfA {ECO:0000303|PubMed:15904941}; ORFNames=CPUR_04077;
OS Claviceps purpurea (strain 20.1) (Ergot fungus) (Sphacelia segetum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Claviceps.
OX NCBI_TaxID=1111077;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=20.1;
RA Florea S., Oeser B., Tudzynski P., Schardl C.L.;
RL Submitted (JUN-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=20.1;
RX PubMed=23468653; DOI=10.1371/journal.pgen.1003323;
RA Schardl C.L., Young C.A., Hesse U., Amyotte S.G., Andreeva K., Calie P.J.,
RA Fleetwood D.J., Haws D.C., Moore N., Oeser B., Panaccione D.G.,
RA Schweri K.K., Voisey C.R., Farman M.L., Jaromczyk J.W., Roe B.A.,
RA O'Sullivan D.M., Scott B., Tudzynski P., An Z., Arnaoudova E.G.,
RA Bullock C.T., Charlton N.D., Chen L., Cox M., Dinkins R.D., Florea S.,
RA Glenn A.E., Gordon A., Gueldener U., Harris D.R., Hollin W., Jaromczyk J.,
RA Johnson R.D., Khan A.K., Leistner E., Leuchtmann A., Li C., Liu J., Liu J.,
RA Liu M., Mace W., Machado C., Nagabhyru P., Pan J., Schmid J., Sugawara K.,
RA Steiner U., Takach J.E., Tanaka E., Webb J.S., Wilson E.V., Wiseman J.L.,
RA Yoshida R., Zeng Z.;
RT "Plant-symbiotic fungi as chemical engineers: Multi-genome analysis of the
RT Clavicipitaceae reveals dynamics of alkaloid loci.";
RL PLoS Genet. 9:E1003323-E1003323(2013).
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, AND IDENTIFICATION IN THE EAS CLUSTER.
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
RP 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 [14]
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 [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [16]
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: Agroclavine dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of fungal ergot alkaloid (PubMed:14732265,
CC PubMed:14700635, PubMed:15904941, PubMed:17308187, PubMed:17720822).
CC DmaW catalyzes the first step of ergot alkaloid biosynthesis by
CC condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-
CC dimethylallyl-L-tryptophan (PubMed:14732265). The second step is
CC catalyzed by the methyltransferase easF that methylates 4-
CC dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine,
CC resulting in the formation of 4-dimethylallyl-L-abrine (By similarity).
CC The catalase easC and the FAD-dependent oxidoreductase easE then
CC transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further
CC oxidized by easD in the presence of NAD(+), resulting in the formation
CC of chanoclavine-I aldehyde (PubMed:20118373, PubMed:21409592).
CC Agroclavine dehydrogenase easG then mediates the conversion of
CC chanoclavine-I aldehyde to agroclavine via a non-enzymatic adduct
CC reaction: the substrate is an iminium intermediate that is formed
CC spontaneously from chanoclavine-I aldehyde in the presence of
CC glutathione (PubMed:20735127, PubMed:21494745). The presence of easA is
CC not required to complete this reaction (PubMed:21494745). Further
CC conversion of agroclavine to paspalic acid is a two-step process
CC involving oxidation of agroclavine to elymoclavine and of elymoclavine
CC to paspalic acid, the second step being performed by the elymoclavine
CC oxidase cloA (PubMed:16538694, PubMed:17720822). Paspalic acid is then
CC further converted to D-lysergic acid (PubMed:15904941). Ergopeptines
CC are assembled from D-lysergic acid and three different amino acids by
CC the D-lysergyl-peptide-synthetases composed each of a monomudular and a
CC trimodular nonribosomal peptide synthetase subunit (PubMed:14700635,
CC PubMed:15904941). LpsB and lpsC encode the monomodular subunits
CC responsible for D-lysergic acid activation and incorporation into the
CC ergopeptine backbone (PubMed:14700635). LpsA1 and A2 subunits encode
CC the trimodular nonribosomal peptide synthetase assembling the
CC tripeptide portion of ergopeptines (PubMed:14700635). LpsA1 is
CC responsible for formation of the major ergopeptine, ergotamine, and
CC lpsA2 for alpha-ergocryptine, the minor ergopeptine of the total
CC alkaloid mixture elaborated by C.purpurea (PubMed:17560817,
CC PubMed:19139103). D-lysergyl-tripeptides are assembled by the
CC nonribosomal peptide synthetases and released as N-(D-lysergyl-
CC aminoacyl)-lactams (PubMed:24361048). Cyclolization of the D-lysergyl-
CC tripeptides is performed by the Fe(2+)/2-ketoglutarate-dependent
CC dioxygenase easH which introduces a hydroxyl group into N-(D-lysergyl-
CC aminoacyl)-lactam at alpha-C of the aminoacyl residue followed by
CC 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 -!- CATALYTIC ACTIVITY:
CC Reaction=agroclavine + NADP(+) = didehydroagroclavine + H(+) + NADPH;
CC Xref=Rhea:RHEA:34059, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:65036, ChEBI:CHEBI:65042; EC=1.5.1.46;
CC Evidence={ECO:0000269|PubMed:21494745};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:21494745}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21494745}.
CC -!- SIMILARITY: Belongs to the fgaFS/easG family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; JN186799; AET79181.1; -; Genomic_DNA.
DR EMBL; CAGA01000020; CCE30229.1; -; Genomic_DNA.
DR AlphaFoldDB; M1WEN5; -.
DR SMR; M1WEN5; -.
DR STRING; 5111.M1WEN5; -.
DR EnsemblFungi; CCE30229; CCE30229; CPUR_04077.
DR VEuPathDB; FungiDB:CPUR_04077; -.
DR eggNOG; ENOG502RYYU; Eukaryota.
DR HOGENOM; CLU_007383_10_6_1; -.
DR OrthoDB; 993213at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000016801; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR019901; Ergot_alkaloid_biosynthesis.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR008030; NmrA-like.
DR Pfam; PF05368; NmrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR03649; ergot_EASG; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..290
FT /note="Agroclavine dehydrogenase"
FT /id="PRO_0000423496"
SQ SEQUENCE 290 AA; 31904 MW; FD0857B72E613A10 CRC64;
MTVLLTGGTG RTAKHIAGIF RQTNVPFLVA SRSSSAGTAE NHRKFDWLDE ETFPNALSVD
QGMKPISVVW LCPPPLYDLA TPVIKFIDFA VSQNVKKFVL LSASVIQKGG PAMGKIHEHL
DSIKDVTYTV LRPTWFMENF STKGEIQCEA IRRDSTVYSA TENGKIPFIS VVDIARVAAC
ALTAETLKNS DHILQGPDLL TYDEVAQALT GVLGRKITHT KMTEGELAEK LMEEGVTPEE
AYMHAAMDSM IKSGSEERVV SDEVKAWTGV KPRGFINFAL SEKAAWRARK
