LPSC_CLAPU
ID LPSC_CLAPU Reviewed; 1633 AA.
AC Q2PBY5;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 1.
DT 23-FEB-2022, entry version 70.
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};
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], IDENTIFICATION IN THE EAS CLUSTER,
RP FUNCTION, AND DOMAIN.
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 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.
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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [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: 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; AJ884677; CAI59267.1; -; Genomic_DNA.
DR VEuPathDB; FungiDB:CPUR_04085; -.
DR UniPathway; UPA00327; -.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
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 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; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..1633
FT /note="D-lysergyl-peptide-synthetase subunit 3"
FT /id="PRO_0000439113"
FT DOMAIN 622..691
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 80..483
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 836..1127
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 1256..1483
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 654
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1633 AA; 179437 MW; 3A92AE420BAEA93A CRC64;
MVVCVLSGKV CYLSYNVTRV SDDQAAHVAA TFETVAKCIA DAPHRLIQEV EVLSQLDVDR
LKTWNAYQPI AVETCYQDLF RQRCDLHPDS PAVVAWDGSF TYDELDHFSS LLATRLQAAG
IGPDVFVTIC ATRCRWIPVA MLGIIKARGA FCALDLSHPL DRLKDICDAL KSTITITTPT
DSNIARKLAS TVIVIGGDAP VESDRITPMN DRPKPTNGHP RNALYSVFTS GSSGKPKGVV
VEHRSFVSSA LASIQPLDIR PHDRLLHFSA YAFDISVFEV LTPLISGATI AIPSEKRRKE
SLTHAVQELG ATWALLTPTV ARLYDPDEFP SLRTLALGGE LAQTSDIALW QSKNVVIIYN
PAECCPIGVS GPACPADGRF LGRSHTCQRA WIVDPRDHDK LLPIGAVGEL LIEGPVVARC
YAHDPNFSSP DSPFIQSTPS WMLRLRSNTS SGTRLYRTGD LARYGSDASL YYMGRKDSQI
KIRGQRTEPG EIESNLHSIL SKDKLGVAIV VLELRGSSKI IAFVSKDTGG LGGDSNTVGQ
LRIEAATEET DMCIIKATSK LHRIMPAYMV PSAFLSVNYI PISRSGKIDR TRLKSFALSL
PQETLLRVNN GLETGDLPES NEEHRLQRMY SLVLGISRDK IGMESDFFRL GGDSLQAMKL
LALAPKEGLT DISYEDIFRY PRLKDLARKA SQSVTIKKDG FGENSSVIHP FSLVIDGQSL
IDMAAKQCNI ERDSIEDIYP CTPMQASIMS LAVKGKIVSF LTFGLALRDH VDTKRVKDTW
HAAYRANSLL RTRIIVCAET GQLYQVVVGG DIFWDDDECG NFAQPESGPS ASIGGPLVRM
KLVEGQLSIA IHRALYDNWS IRQLLNDISG AYNGLPLPSR PSFNCYVSYA AKSLEAASSF
WSAELGDADL DAAKYPEPVS QNSHTNSRAW LGIRVVTCQK ESIDVLASEF RLAWAMITYA
RTNKKDVVFG VLSSGRSNAS KDTKEIMGPI ATVTPLRVTI DGTQDVGGAL EELQYRQEEQ
AMYTHLGLRR IGQLGRNAAA ACQIQTVLIV EPDLPDLRGV WFSNDATLPN HSDADASNYR
LTIKCVVGPD CTDIFAIFDH QSLPIMEVKE ILSQFEHILG QIHGKEASQL SVASIDTANF
KDWDTLHKST EMPSVCRNGL LLSDPTFLPH DQMKTFPAIE EAAAHCVFQD SLQEASIARD
AKMQPKEPLS SADLISEINR YDLAXXRSRP SPESILLSEL ALTGESHSSG THTVFVTGAS
GFIGTQILRH CLEDPRIDHV IALVRGSSAN EARSRTEESA RRAQWWSDCH SQKLEVWPGD
LAMPHLGLNE THWRRLADRT TINAIIHNGA SVHWLKRYAD LEATNVGATA QLLQLAVANP
RLGFVYVSSG RYTDPNAEAE EPAAANVAAT AMPYSQTKFV AESPIRRTAA RLPHGQTQVR
IISLGLVIGD PLTGVVNADD YLWRLIATCV QAGEYNSSAG SEWMPISDVT STALAIVQTA
LNPAGVPATI KPITGGLMWS EIWDLVTDMG YDMEPRPESE WMATVRRDLK REQEKHPLWT
LSHLVESRSQ LNTDAGAGSA WADAWRGDEA TTRNLRTAFR RSLRFLGEVG FLPGQKGRNT
DGEVNGRAFR RAW
