ID LPSC_CLAP2 Reviewed; 1792 AA.
AC M1VVW6; G8GV59;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 27-MAR-2024, entry version 46.
DE RecName: Full=D-lysergyl-peptide-synthetase subunit 3 {ECO:0000305|PubMed:15904941};
DE Short=LPS3 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:19139103};
DE AltName: Full=Ergot alkaloid synthesis protein lpsC {ECO:0000303|PubMed:17720822};
DE AltName: Full=Nonribosomal peptide synthetase 3 {ECO:0000303|PubMed:15904941};
GN Name=lpsC {ECO:0000303|PubMed:17720822};
GN Synonyms=cpps3 {ECO:0000303|PubMed:15904941}; ORFNames=CPUR_04085;
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 IDENTIFICATION IN THE EAS CLUSTER, FUNCTION, AND DOMAIN.
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, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
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.
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: D-lysergyl-peptide-synthetase subunit 3; part of the gene
CC cluster 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 -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:19139103}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module (PubMed:14700635). Each module is responsible for the
CC recognition (via the A domain) and incorporation of a single amino acid
CC into the growing peptide product (PubMed:14700635). Thus, an NRP
CC synthetase is generally composed of one or more modules and can
CC terminate in a thioesterase domain (TE) or reductase domain (R) that
CC releases the newly synthesized peptide from the enzyme
CC (PubMed:14700635). LpsC is composed of only one module which is
CC required for the activation of D-lysergic acid activation and its
CC incorporation in the final ergot alkaloid (PubMed:19139103).
CC {ECO:0000269|PubMed:14700635}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JN186799; AET79177.1; -; Genomic_DNA.
DR EMBL; CAGA01000020; CCE30237.1; -; Genomic_DNA.
DR AlphaFoldDB; M1VVW6; -.
DR SMR; M1VVW6; -.
DR STRING; 1111077.M1VVW6; -.
DR VEuPathDB; FungiDB:CPUR_04085; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_60_3_1; -.
DR OrthoDB; 3305653at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000016801; Unassembled WGS sequence.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd05918; A_NRPS_SidN3_like; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 1.
DR Gene3D; 3.40.50.12780; N-terminal domain of ligase-like; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 2.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR NCBIfam; TIGR01746; Thioester-redct; 1.
DR PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 3.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1792
FT /note="D-lysergyl-peptide-synthetase subunit 3"
FT /id="PRO_0000439114"
FT DOMAIN 779..853
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 239..642
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 895..1285
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 1415..1640
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 813
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1792 AA; 197314 MW; 1D7DA13C3EB84A94 CRC64;
MNSIKLKFNC KDSLWQEHIG AGDFSFAAIF LTTWGIVLRA YLDTDDVFFE YGLSRCEPVS
QRDGIDELVP DRPFNLKFDG SMTVKDTIRR ADSVVYGTPL VQDGLEHETH RETDPKRETF
YSTCMLFLDG PKSPIDADVV EGTILDDIEF EMKPVVNYDM VVYVLSGKVC YLSYNVTRVS
DDQAAHVAAT FETVAKCIAD VPHRLVQEVE SLSQLDVDRL KTWNAYQPIA VETCYQDLFR
QRCDLHPNSP AVIAWDGSFT YDELDHFSSL LATRLQAAGI GPDVFVTICA TRCRWIPVAM
LGIIKARGAF CALDLSHPLD RLKDICDALK STITITTPTD SNIARKLAST VIVIGGDAPV
ESDRITPMND RPKPINGHPT NALYSVFTSG SSGKPKGVVV EHRSFVSSAL ASIQPLDIRP
HDRVLHFSAY AFDISVFEVL TPLISGATIA IPSEKRRKES LTHAVQELGA TWALLTPTVA
RLYDPDEFPS LRTLALGGEL AQASDIALWQ SKNVVVIYNP AECCPIGVSG PACPADGKFL
GWSHTCQRAW IVDPRDHDKL PPIGAVGELL IEGPVVARCY AHDPNFSSPD SPFIQSTPSW
MLRLRSNTPS GTRLYRTGDL ARYGSDASLY YMGRKDSQIK IRGQRTEPGE IESNLHSILS
KDKLGVAIVV LELRGSSKII AFVSKDTGGL GGDSNTVGQL RIEAATEETD VCITKATSKL
HSIMPAYMVP SAFLSVNYIP ISRSGKIDRT RLKSFALSLP QETLLRVNNG LETGDLPESN
EEHRLQRMYS LVLGISRDKV GMESDFFRLG GDSLQAMKLL ALAPKEGLTD ISYEDIFRYP
RLKDLARKAS QSVTIKKDGF GENSSVIHPF SLVIDGQSLI DMAAKQCDIE RDSIEDIYPC
TPMQASIISL AVKGKIMPFL TFGLALRDHV DTKRVKDTWH AAYRANSLLR TRIIVCAETG
QLYQVVVGGD IFWDDDECGN FAQPKSGPSA SIGGPLVRMK LVEGQLSIAI HRALYDNWSI
RQLLNDISGA YNGLTLPSRP SFNCYVSYAA RSLEAASSFC NAELGDSDLD AAKYPEPVSQ
NSHTNFRAWL GIRVFTCQKE SIDVLASEFQ LAWAMIAYAR TNKKDVVFGV LSSGRSNASK
DTKEIMGPIA TVTPLRVTID GTQDVGGALE ELQYRQEEQA MYTHLGLRRI GQLGRNAAAA
CQIQTVLIVE PDLPDLRGVW FSNDATLPNH SDADASNYRL TIKCVVGPDC TDIFAIFDHQ
SLPIMEVKEI LSQFEHILGQ IHGKEASQLS VASIDTVNFK DWDTLHKLTE MPSVCRNGLL
LSDPTILPQG QMKTFSAVEE AAAHCAFQDS LQEASIARDA KMQPKEPLSS ADLISEINRY
DLAIMRSRPS PESILLSELA LTGDSHSSGT HTVFVTGANG FIGTQILRHC LEDPTIDRVI
ALVRGSSANE ARSRTEESAR RAQWWSDCHS QKLEVWPGDL AMPHLGLNET HWRRLADRTT
INAIIHNGAS VHWLKRYADL EATNVGATAQ LLQLAVANPR LGFVYVSSGR YTDPNAESEE
PAAANVAATA MPYSQTKFVA ESLIRRTAAR LPHGQTQVRI ISLGLVIGDP LTGVVNADDY
LWRLIATCVQ AGEFNSSAGS EWMPISDVTS TALAIVQTAL NPAGVPATIK PITGGLMWSE
IWDLVTDMGY DMEPRPESEW MATVRRDLER EQERHPLWTL SHLVESRSQL NTDAGAGPAW
ADAWRGDEAT TRNLKTAFRR SLRFLGEVGF LPGQKGQNTD GEVNGRAFTR AW
//
