LPSA1_EPIFI
ID LPSA1_EPIFI Reviewed; 3589 AA.
AC Q96V34;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 23-FEB-2022, entry version 88.
DE RecName: Full=D-lysergyl-peptide-synthetase subunit 1 {ECO:0000303|PubMed:11592979};
DE Short=LPSA {ECO:0000303|PubMed:11592979};
DE EC=2.3.1.- {ECO:0000305|PubMed:11592979};
DE AltName: Full=Ergot alkaloid synthesis protein lpsA {ECO:0000305|PubMed:11592979};
DE AltName: Full=Nonribosomal peptide synthetase lpsA {ECO:0000303|PubMed:11592979};
GN Name=lpsA {ECO:0000303|PubMed:11592979};
OS Epichloe festucae var. lolii (Neotyphodium lolii) (Acremonium lolii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX NCBI_TaxID=73839;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11592979; DOI=10.1073/pnas.221198698;
RA Panaccione D.G., Johnson R.D., Wang J., Young C.A., Damrongkool P.,
RA Scott B., Schardl C.L.;
RT "Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by
RT genetic modification of the endophyte.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12820-12825(2001).
RN [2]
RP FUNCTION.
RC STRAIN=Lp19;
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).
CC -!- FUNCTION: D-lysergyl-peptide-synthetase subunit 1; part of the gene
CC cluster that mediates the biosynthesis of fungal ergot alkaloid
CC ergovaline, the predominant ergopeptine product in E.festucae var.
CC lolii (PubMed:17308187). DmaW catalyzes the first step of ergot
CC alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP)
CC and tryptophan to form 4-dimethylallyl-L-tryptophan (By similarity).
CC The second step is catalyzed by the methyltransferase easF that
CC methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-
CC L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine
CC (By 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 (By similarity). Agroclavine
CC dehydrogenase easG then mediates the conversion of chanoclavine-I
CC aldehyde to agroclavine via a non-enzymatic adduct reaction: the
CC substrate is an iminium intermediate that is formed spontaneously from
CC chanoclavine-I aldehyde in the presence of glutathione (By similarity).
CC The presence of easA is not required to complete this reaction (By
CC similarity). Further conversion of agroclavine to paspalic acid is a
CC two-step process involving oxidation of agroclavine to elymoclavine and
CC of elymoclavine to paspalic acid, the second step being performed by
CC the elymoclavine oxidase cloA (By similarity). Paspalic acid is then
CC further converted to D-lysergic acid (By similarity). Ergovaline is
CC assembled from D-lysergic acid and three different amino acids by the
CC D-lysergyl-peptide-synthetase composed of a monomudular (lpsB) and a
CC trimodular (lpsA) nonribosomal peptide synthetase subunit
CC (PubMed:17308187, PubMed:11592979). {ECO:0000250|UniProtKB:Q50EL0,
CC ECO:0000269|PubMed:11592979, ECO:0000269|PubMed:17308187}.
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000305|PubMed:11592979}.
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 (By similarity). Each module is responsible for the recognition
CC (via the A domain) and incorporation of a single amino acid into the
CC growing peptide product (By similarity). Thus, an NRP synthetase is
CC generally composed of one or more modules and can terminate in a
CC thioesterase domain (TE) or reductase domain (R) that releases the
CC newly synthesized peptide from the enzyme (By similarity). LpsA1 has a
CC domain arrangement (A-T-C-A-T-C-A-T-Cyc) with 3 A and 3 peptidyl
CC carrier (PCP/T) domains, 2 C-domains, and a terminal domain called the
CC Cyc domain (By similarity). The Cyc domain has limited similarity to
CC both C and Cy domains of NRPS but is most different in the so-called C3
CC and Cy3 motif of the latter domains, suggesting a special mechanism in
CC acyl diketopiperazine formation, which is the final step of D-lysergyl
CC peptide lactam synthesis (By similarity). LpsA misses an N-terminal C
CC domain in the first module, leading to the conclusion that this C
CC domain is located on the other subunit (lpsB) containing the D-lysergic
CC acid module (By similarity). {ECO:0000250|UniProtKB:O94205}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of ergovaline
CC (PubMed:11592979). {ECO:0000269|PubMed:11592979}.
CC -!- SIMILARITY: Belongs to the NRP synthetase 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; AF368420; AAL26315.2; -; Genomic_DNA.
DR SMR; Q96V34; -.
DR UniPathway; UPA00327; -.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
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; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 3.
DR Gene3D; 3.40.50.12780; -; 3.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 3.
DR Pfam; PF00668; Condensation; 4.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Ligase; Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3589
FT /note="D-lysergyl-peptide-synthetase subunit 1"
FT /id="PRO_0000439107"
FT DOMAIN 883..952
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1974..2042
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3064..3132
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 344..742
FT /note="Adenylation (A) domain 1"
FT /evidence="ECO:0000255"
FT REGION 995..1380
FT /note="Condensation (C) domain 1"
FT /evidence="ECO:0000255"
FT REGION 1424..1826
FT /note="Adenylation (A) domain 2"
FT /evidence="ECO:0000255"
FT REGION 2087..2509
FT /note="Condensation (C) domain 2"
FT /evidence="ECO:0000255"
FT REGION 2534..2929
FT /note="Adenylation (A) domain 3"
FT /evidence="ECO:0000255"
FT REGION 3187..3585
FT /note="Cyclization (Cyc) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 915
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2006
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3096
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3589 AA; 394889 MW; 8B8051761A23841B CRC64;
MGSTTVEPVG STYARPKPLG NLDHRIEQLL GSESVLNESP GHSPNAYGIP YTARNLTLED
VDHCKSLTNK DLSLEFWKSH LQTAKPCILT RLKPGTGSSI LSSRQSVKVD LGGVNTTCRN
LFDSTGISLM TVFKVAWGMV LSTYTGSDHV CFGYGAARPS MSVDGEQTTI KPLIKMLPCD
MLFKGGTTLL GTVHKAESDF ICTIPYQSVS IAEIHHGIGT ESGALFNTSI IFWPQEDFSD
NPITEVLSQK VTETESLTEC DIIMHVDSKQ QCYLSYWDYF LSDEQANHLA GALNVAMKSI
FESPHRPVGQ VEMFSYLDQQ KLLQWNGQAP IASESCLGDL IGQNCHSRPD SLAVDSWDGF
FTYQELDRLS STLANKLRCA GVGPDVFVTA CFDRCKWMPV AMLGIIKAGG AICALDPSYP
LGRLTGMCQL LKSTVVLTTA NNAQQAEQLA LTTIVLGNDL WTGDSYDEQE RQAPLSNVCP
SNALYAVFTS GSTGKPKGVV VEHRSFSSCA LASLKPLDIR PHDRVLHISS YAFDISIFET
LATLTAGASV AIPSEKARRE DLPGAMRELQ ATWAFLTPTV ARMYQPKDFP SLRTLCLGGE
AIHTSDIGLW ASKNLVTGYN PAESCPLGIS GPADKSAASF LGWSFSSQAS WIVDPRDYQK
LAPIGAVGEL MIEGPAVARG YIHDLTCSHP DSPFVLPPPQ WLSRFRASTS QDTRLYRTGD
LVQYGSNGSV HFIGRKDLQV KVHGQRVELS EIEFQLHKTL LPLDCKVVVD AVTFTGHTSV
IAFITAAEHS DLENEDDAVR SPDVKVITQD FEIRAADAAT KLQSILPRHM VPTIYLPVGH
IPMSRSGKID RQKLRSLALS LPRETLYHIG RQPGPGEIVV TDVERRLQLL FAQVLDLSPE
KIKADSDFFR LGGDSIYAMK LLALAPQQGP RDLTYEEIFR HPKLRDLAAA SSSFSNISLA
IPEDLGPAPF SLARDADSLT KIASEQCGVA VGDIEDIYPC TSLQESLIAS TAHDQDAYVG
VQSFTLNDDI DTTRLKMAWK MTSEGHPILR TRIIQTDSGA PYQAVIRGPL SWSEESSSDD
LPPQFQPSIG LGTPLVQLCL TNSRLLVAMH HALYDGWSLP LLLAEVDQAY RQLSVRQLPP
FNRYVKHVTE TVDSAASFWK AELQDADPVD FPPLPHLNYK PEPRALLTKS ITLTAHTNSQ
HNVTLATELQ LAWALTSHTY TNSQDVVFGI ISSGRGAPVA GIERMLGPTF ASTPLRVPLD
PAQDVREALE ELQYRLAEQT KYVQIGLQRI RQQGPNAAAA CSFQTMLVVE PNQPVKTQSA
WFSRHEFLSE LTRFSSHSLT LRCKLLAGSV EVTAIYDQLV VPDAQMQRIL SQFQHILTQI
QGIGSRDTTI GDIDRLSSGD WNELQAWNST LPPGLELSVH QMVQAKAQMQ PEALAIHSWD
GDLTYKELED YAKGLANRLH ALGVRPNTFV AIYLQKSLWV VVAQLAVLIA GAAFTTLETS
QPINRLRDVC RTVQPTVVLT SDKLRLSGAD LEVPAPLLVI NQQLLLEEPG SHSRPLENHT
IMASDAMYSI ATSGTTGKPK VVVIEHQAFL ANSKHLIDRW GFTADSRVLQ FAGYSFDAMI
VEHFITLLAG GCICIPSSFD RDNRLATCIV EMRVNWAMLT SSVIPLFTPA AVPTLQTLVQ
AGEPMHQGIT DCWASHVQLF NAYGPTECSV ISTTSNIINP DARNPRNIGF TTGGVCWIVD
PENPESPPVP IGAEGELIIE GAILARGYLG DRVRTAAAFT LRPGWLDDFR GSSGDNRIYR
TGDIVRYDPD GSISYVRRKD SQVKLRGQRV ELLDVEHHLQ NCFPGALQVV ADIVTVPNTQ
SSALVALVLA TPTSSSSVAI ESCSNDDQAT TAHGLLLLAN NPQFLIDASA AELALQDRVP
SYMVPSLFIP TSRFPRDVSG KVNRGEITRS LAALSRQEWD GYVSTNRVAP TSGLERELQK
IWARILNIPP DTIGVHDSFF RLGGDSITCM QVAAQCSRTG ILITVKDIFK RRTIEKLAAA
AVVVQCPESS TTERVNTAEA KFSFYGPGQL EEYMIQIQPQ LGEGQVVEDI YPCSPIQRGI
LMSHARNSGN YEEVIQWKVI SRAPVDVCRL RDAWAQVVDR HAVLRTLFLH VCKENYLDQV
VLRSHSPMVL VYNEGEEPVN PVSTGCSQPM HHLRVKRSSA GGITVRLHIN HALVDGASLF
IIRRDLAMAY EGRLASSRAS SPYRDYIAYL QNCHSQIQSN EYWQSYMEGT APCLFPTLKN
AGAQDSQQPF EAFTLQLGAT ADLNQFCENH RLALTSVLHV VWAMVVQRYT AMDEVCFGYM
TSGRHVPVAG VQDIVGPLFN MLVARVGLPH DATLLSVMQK YHDNFLISLD HQHQSLAETL
HSIGSASGEL FNTLVSIFND QREGEPAHKS SAVTLVGDDI HSRSEYAITL NVLMLADQVH
IQLSYHTSWL SDNYARMIAE TFRHVLATVL GQPQLRLNEI EMLDEEHRSG LYGRNHAAVP
SFDSCIHYTI HQRCLESPES PAICAWDGDF SYRRLDQLSS SLAEELIGHG VGVEMTIPVL
LEKTCWTPVA MLAVLKSGAS FVLMDASHPL GRLQTICEAI NPPVILASPQ TRSKAVGLTS
HVIEVTNRLL EQEQAEQQQT WPRVVTKGSN AAYVVFTSGS TGKPKGAIVD HSCLATAAGH
LPSRMYINSA SRVLQFSSHA WDIPVTDVLL TLRVGGCVCI PSDEERIGNL AQVANRMMVN
WALLTPTVAR LVKPEDFTHL QTLVLAGEAV SSTDLTTWHD KVRLIQGYGP AECSLVSTVS
EPLTPSDNPR NIGQPNGCVA WVVHRDNHHL LAPSGAIEEL VLEGPIVSRG YINDPERSAA
VFVDPPTWLT RLRGGHSPTR LYKTGDLVSA GLDGCLSFVG RKDDQVKIRG QRVELGEVEA
LASQAFPGSH VVVETVKDLS STILVAFILQ KETAHAQPSS ISSLLHPPSP LFRELISAAS
CSLRETMPSF MIPTVFLPLA HLPKAPTGKT DRKFLRGHVA SLSRMELEAY SIVDATGRAP
STPLETRLQE LVGRVLHRSP ESIPLDEDLF TFGLDSLTAM TLATLVREDG LAISVPTIFQ
RPRLSELAVV LNQEQQIKQG QFLAPPPNAL MASMDELCAQ WQLDRSQVVN IAPTTYYQRG
SLASHHTNFI ALHFSQPLDP IPFRNAVVGL VQKHAILRTA FVPFRETFVQ LILRDFDLPV
QEIRTDEDDP SVVAESFCRE ADRVPVSFGT PITQLYMILG RAGDRLSAVL RLQRAQYDGV
AVSCMIADLR SAFDEAPSSA LPTLEYADYV ISRRAHSSPP VFQVWRELLQ GSSMTYLVPP
TEYIRSTDRS RTELLVTSSC DIPMPDTKGG ITMATVIKTA WALCLARQTQ SKDVVFAQLV
RNRHLAIAGI DRTVGPCINY VPVRASLNLD WTAKEFLHWV QRQHIRTMTC DMADWDDLVI
ESTSWPRDTE LGSAVHYLSA PVASDYTFAG DVPCQFQMYD FKMVHTYPMV TCLPFPSVGD
SSLTVLKIIL TSAVFGQGVA DRLLSLFRDM VHRLTTYPES LVSELLIIR
