DMAW_CLAPU
ID DMAW_CLAPU Reviewed; 448 AA.
AC P0CT20; O94204; Q6X2E0; Q9C140;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Tryptophan dimethylallyltransferase 1 {ECO:0000305};
DE EC=2.5.1.34 {ECO:0000269|PubMed:14732265};
DE AltName: Full=4-dimethylallyltryptophan synthase 1 {ECO:0000303|PubMed:10071219};
DE Short=DMATS 1 {ECO:0000303|PubMed:10071219};
DE AltName: Full=All-trans-hexaprenyl-diphosphate synthase 1 {ECO:0000305};
DE AltName: Full=L-tryptophan dimethylallyl transferase 1 {ECO:0000305};
GN Name=dmaW {ECO:0000303|PubMed:17720822};
GN Synonyms=cpd1 {ECO:0000303|PubMed:10071219}, dmaW1;
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] (ISOFORM 1), IDENTIFICATION IN THE EAS
RP CLUSTER, AND FUNCTION.
RC STRAIN=P1 / 1029/N5;
RX PubMed=10071219; DOI=10.1007/s004380050950;
RA Tudzynski P., Hoelter K., Correia T.H., Arntz C., Grammel N., Keller U.;
RT "Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.";
RL Mol. Gen. Genet. 261:133-141(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
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 [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, 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.
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: Tryptophan dimethylallyltransferase; part of the gene cluster
CC that mediates the biosynthesis of fungal ergot alkaloid
CC (PubMed:10071219, PubMed:14732265, PubMed:14700635, PubMed:15904941,
CC PubMed:17308187, PubMed:17720822). 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:14732265). 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:20118373, PubMed:21409592). Agroclavine dehydrogenase
CC easG then mediates the conversion of chanoclavine-I aldehyde to
CC agroclavine via a non-enzymatic adduct reaction: the substrate is an
CC iminium intermediate that is formed spontaneously from chanoclavine-I
CC aldehyde in the presence of glutathione (PubMed:20735127,
CC PubMed:21494745). The presence of easA is not required to complete this
CC reaction (PubMed:21494745). Further conversion of agroclavine to
CC paspalic acid is a two-step process involving oxidation of agroclavine
CC to 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:10071219, ECO:0000269|PubMed:14700635,
CC ECO:0000269|PubMed:14732265, ECO:0000269|PubMed:15904941,
CC ECO:0000269|PubMed:16538694, ECO:0000269|PubMed:17560817,
CC ECO:0000269|PubMed:19139103, ECO:0000269|PubMed:20118373,
CC ECO:0000269|PubMed:20735127, ECO:0000269|PubMed:21409592,
CC ECO:0000269|PubMed:21494745, ECO:0000269|PubMed:24361048,
CC ECO:0000305|PubMed:17308187, ECO:0000305|PubMed:17720822}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + L-tryptophan = 4-(3-methylbut-2-
CC enyl)-L-tryptophan + diphosphate; Xref=Rhea:RHEA:14173,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58209; EC=2.5.1.34;
CC Evidence={ECO:0000269|PubMed:14732265};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:14732265}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q50EL0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Short;
CC IsoId=P0CT20-1; Sequence=Displayed;
CC Name=2; Synonyms=Long;
CC IsoId=P0CT20-2; Sequence=VSP_011244;
CC -!- BIOTECHNOLOGY: D-lysergic acid amides have been used as medicinal
CC agents for a long time. The pharmacological effects of the various
CC ergot alkaloids and their derivatives are due to the structural
CC similarity of the tetracyclic ring system to neurotransmitters such as
CC noradrenaline, dopamine or serotonin. In addition to migraine or blood
CC pressure regulation, there is a wide spectrum of potential new
CC applications of this interesting group of compounds.
CC {ECO:0000305|PubMed:11778866}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AJ011963; CAB39314.1; -; Genomic_DNA.
DR EMBL; AY259840; AAP81209.1; -; Genomic_DNA.
DR EMBL; AY259840; AAP81210.1; -; Genomic_DNA.
DR AlphaFoldDB; P0CT20; -.
DR SMR; P0CT20; -.
DR VEuPathDB; FungiDB:CPUR_04076; -.
DR BioCyc; MetaCyc:MON-15629; -.
DR UniPathway; UPA00327; -.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProt.
DR GO; GO:0050364; F:tryptophan dimethylallyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0035837; P:ergot alkaloid biosynthetic process; IEA:InterPro.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR InterPro; IPR012148; DMATS-type_fun.
DR InterPro; IPR017796; Trp_dimethylallylTrfase.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR PIRSF; PIRSF000509; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
DR TIGRFAMs; TIGR03430; trp_dimet_allyl; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Alternative splicing; Transferase.
FT CHAIN 1..448
FT /note="Tryptophan dimethylallyltransferase 1"
FT /id="PRO_0000181364"
FT BINDING 80..81
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 89
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 190
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 249
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 262
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 264
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 266
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 348
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 350
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 414
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT BINDING 418
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q50EL0"
FT VAR_SEQ 1
FT /note="M -> MCETEVDSLSCPKVNAA (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_011244"
SQ SEQUENCE 448 AA; 51673 MW; 625709FAAF269242 CRC64;
MSTAKDPGNG VYEILSLIFD FPSNEQRLWW HSTAPMFAAM LDNAGYNIHD QYRHLGIFKK
HIIPFLGVYP TKDKERWLSI LTRCGLPLEL SLNCTDSVVR YTYEPINEVT GTEKDTFNTL
AIMTSVQKLA QIQAGIDLEW FSYFKDELTL DESESATLQS NELVKEQIKT QNKLALDLKE
SQFALKVYFY PHLKSIATGK STHDLIFDSV LKLSQKHDSI QPAFQVLCDY VSRRNHSAEV
DQHGALHARL LSCDLIDPAK SRVKIYLLEK TVSLSVMEDL WTLGGQRVDA STMDGLDMLR
ELWSLLKVPT GHLEYPKGYL ELGEIPNEQL PSMANYTLHH NDPMPEPQVY FTVFGMNDAE
ISNALTIFFQ RHGFDDMAKN YRVFLQDSYP YHDFESLNYL HAYISFSYRR NKPYLSVYLH
TFETGRWPVF ADSPISFDAY RRCELSTK
