EASG_CLAPU
ID EASG_CLAPU Reviewed; 290 AA.
AC P0CT21; G8GV67; Q5G5T7;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 25-MAY-2022, entry version 25.
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};
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].
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
RA Machado C., Schardl C.L.;
RT "Studies of ergot alkaloid biosynthesis genes in Clavicipitaceous fungi.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
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 [4]
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 [5]
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 [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.
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 [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBUNIT.
RC STRAIN=ATCC 20102 / Farmitalia FI 32/17;
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 [15]
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}.
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DR EMBL; AY836771; AAW57089.1; -; Genomic_DNA.
DR AlphaFoldDB; P0CT21; -.
DR SMR; P0CT21; -.
DR KEGG; ag:AAW57089; -.
DR VEuPathDB; FungiDB:CPUR_04077; -.
DR BRENDA; 1.5.1.46; 1445.
DR UniPathway; UPA00327; -.
DR GO; GO:0016646; F:oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR GO; GO:0035837; P:ergot alkaloid biosynthetic process; IDA:UniProtKB.
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.
FT CHAIN 1..290
FT /note="Agroclavine dehydrogenase"
FT /id="PRO_0000422558"
SQ SEQUENCE 290 AA; 31890 MW; AD90F03A9996E440 CRC64;
MTVLLTGGTG RTAKHIAGIF RQTNVPFLVA SRSSSAGTAE NHRKFDWLDE ETFPNALSVD
QGMKPISVVW LCPPPLYDLA TPVIKFIDFA VSQNVKKFVL LSASVIQKGG PAMGKIHGHL
DSIKDVTYTV LRPTWFMENF STKGEIQCEA IRRDSTVYSA TENGKIPFIS VVDIARVAAC
ALTAETLKNS DHILQGPDLL TYDEVAQALT GVLGRKITHT KMTEGELAEK LMEEGVTPEE
AYMHAAMDSM IKSGSEERVV SDEVKEWTGV KPRGFINFAL SEKAAWRARK
