ID   PERA_EPIFF              Reviewed;        2773 AA.
AC   Q4H424;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 2.
DT   03-AUG-2022, entry version 86.
DE   RecName: Full=Peramine synthetase {ECO:0000303|PubMed:16091042};
DE            EC=6.3.2.- {ECO:0000305|PubMed:16091042};
DE   AltName: Full=Nonribosomal peptide synthase perA {ECO:0000303|PubMed:16091042};
DE            Short=NRPS perA {ECO:0000305};
DE   AltName: Full=Peramine biosynthesis cluster protein A {ECO:0000303|PubMed:16091042};
GN   Name=perA {ECO:0000303|PubMed:16091042};
OS   Epichloe festucae (strain Fl1).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX   NCBI_TaxID=877507;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=Fl1;
RX   PubMed=16091042; DOI=10.1111/j.1365-2958.2005.04747.x;
RA   Tanaka A., Tapper B.A., Popay A., Parker E.J., Scott B.;
RT   "A symbiosis expressed non-ribosomal peptide synthetase from a mutualistic
RT   fungal endophyte of perennial ryegrass confers protection to the symbiotum
RT   from insect herbivory.";
RL   Mol. Microbiol. 57:1036-1050(2005).
RN   [2]
RP   INDUCTION.
RX   PubMed=20519633; DOI=10.1104/pp.110.158451;
RA   Eaton C.J., Cox M.P., Ambrose B., Becker M., Hesse U., Schardl C.L.,
RA   Scott B.;
RT   "Disruption of signaling in a fungal-grass symbiosis leads to
RT   pathogenesis.";
RL   Plant Physiol. 153:1780-1794(2010).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC       mediates the biosynthesis of peramine, a pyrrolopyrazine synthesized in
CC       association with the grass host that protects the plant from insect
CC       herbivory (PubMed:16091042). The single multifunctional NRPS perA seems
CC       to be responsible for all catalytic steps in the biosynthesis of
CC       peramine (PubMed:16091042). The condensation domain of perA is proposed
CC       to catalyze formation of a peptide bond between 1-pyrroline-5-
CC       carboxylate and arginine (PubMed:16091042). The methylation domain of
CC       perA would catalyze the N-methylation of the alpha-amino group of
CC       arginine (PubMed:16091042). The reductase domain is proposed to be
CC       responsible for reduction of the thioester and the cyclization to form
CC       an iminium ion resulting in release from the peptide synthetase
CC       (PubMed:16091042). Deprotonation of this intermediate and oxidation of
CC       the pyrroline ring would give rise to peramine (PubMed:16091042). This
CC       final oxidation to give the pyrrole functionality may be spontaneous
CC       (PubMed:16091042). {ECO:0000269|PubMed:16091042}.
CC   -!- INDUCTION: Expression is down-regulated when the stress-activated
CC       mitogen-activated protein kinase (sakA) is deleted (PubMed:20519633).
CC       {ECO:0000269|PubMed:20519633}.
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) that releases the newly synthesized peptide
CC       from the enzyme (By similarity). Occasionally, methyltransferase
CC       domains (responsible for amino acid methylation) are present within the
CC       NRP synthetase (By similarity). PerA has the following architecture: A-
CC       T-C-A-Met-T-TE (PubMed:16091042). {ECO:0000250|UniProtKB:A0A144KPJ6,
CC       ECO:0000305|PubMed:16091042}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of peramine and results in
CC       host susceptibility to insect herbivory (PubMed:16091042).
CC       {ECO:0000269|PubMed:16091042}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; AB205145; BAE06845.2; -; Genomic_DNA.
DR   SMR; Q4H424; -.
DR   BioCyc; MetaCyc:MON-19034; -.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 3.
DR   Gene3D; 3.30.559.10; -; 1.
DR   Gene3D; 3.40.50.12780; -; 2.
DR   Gene3D; 3.40.50.150; -; 1.
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; IPR013120; Far_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR010080; Thioester_reductase-like_dom.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF00668; Condensation; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00823; PKS_PP; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR   TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   2: Evidence at transcript level;
KW   Ligase; Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW   Phosphoprotein; Repeat; Transferase.
FT   CHAIN           1..2773
FT                   /note="Peramine synthetase"
FT                   /id="PRO_0000444311"
FT   DOMAIN          774..850
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:16091042"
FT   DOMAIN          2267..2345
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:16091042"
FT   REGION          246..644
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:16091042"
FT   REGION          888..1301
FT                   /note="Condensation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:16091042"
FT   REGION          1321..1720
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:16091042"
FT   REGION          1810..1949
FT                   /note="Methylation (Met) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:16091042"
FT   REGION          2250..2271
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2397..2715
FT                   /note="Thiesterase (TE) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:16091042"
FT   MOD_RES         811
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         2304
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2773 AA;  304992 MW;  B5DADC76CB80608B CRC64;
     MDAEPFDEVD EYTTYPSLPA SVICPVADTK TRYELSWQPS GHHPQEEGDD CAVVTLVYAA
     WALMASRMTS SERVVFDTID GRPDRPAARP LRVLCASSQT VGEYLQALRA HTSSEESYMA
     SPDCKSKRHP TSSTLIATRT SGDAKSSNGT IGNGLPSLAG YPLVLDLQLR GSRLQATAMS
     DSRCTEPWIV FRLLIRLEYC MKGLHEADSR TRLADIDLMS PDDVEQIWKW NGTLPAAVER
     CMHDMFEDQV YSQPLALAVD AWDGRLTYKE LDELSEKLAG HLIDADVGPE VIVPLCFEKS
     MWMPIAMLGV LKAGGSFTLL EPSFPEQRLR TIVEKVNASV MISSPSNMSL SSRLLKRVVE
     LDSCSVKSFS AHPSRPRNSQ PSSTAMFAVF TSGSTGVPKG AILTHTNYSS ALAYQLQPLG
     FTKDSRVFDF ASYAFDVSVH NVFATLTSGA CLCIPSDEDR HNDISKVMVD MRVTISHLTP
     SVTRLIDPDS QPFLKTMVFT GEPLSVDDAT RWWGKVDVVN EYGPAECTIN TVNSRPISPE
     AATNIGLPVG VAAWITDPEN HQVLVPIGCV GELLVEGPLV GRGYIGDPIK TAASFIQDPK
     WLLRGVSGHP GRKGRLYKTG DLVRYCADGS LSYLGRKDAQ VKIRGQRVHL GDVEHWTQVC
     MPEAQRVFAD VIEPQAISPV PTLAVFVQSP EMGENTATNE RPVQIRALRA DVQAKLSQHL
     PSYMVPTVSF WMETLPMTPT GKMDRRMLRR IGSSFSAEQL AQARADRRDG PKRQPTCEME
     ERMRNIWARV LGMLPQDIHL ESNFFHLGGD SIASMRVVAY ARRLGIQVMV ADVFQHPSLH
     DLAKNCSQTL ARAPEDIPAF SLLGPHFNHA LFVQDMSTRY ALDPMTIQDA YPCTRLQEGL
     MFLTSKRPGD YIEQNVLELA RDLSLEGLRN AWEQAVKAMP ILRTRIAQHN HVGLVQLVLD
     DTADWDEAKG LEKYLAADRK RSMGLGEPLS RFALVRDEEG TCKWLVWTIH HAIYDGWSIR
     LVTDAVAEAY GGRSIPQGPQ FQAFIKYVQD QDERAAVNYW QRNLQGFDSA PFPPNVPSVD
     QPVADAAVAH SFATPSGAHG CITTSMLIRA AWALVVGRMA NSNDVVFGST LHGRNAAVNG
     LDEMVAPTIA TIPVRVRFCS TQYVPSYLQA ITQEAAEMMP YEQTGLQRIA ALSSDAEKAC
     KFQTHVVIQP EDCIPGRSLL GQWRSDSQDQ WFSTYALTVE VWLRSDDIFA SAMFDSRTIQ
     SWVVTGMLQR LEWTMHQLHH ATPSQTLGEI NMSSAEDLEQ IWQWNERVPE PVNRCIHDLL
     ADQVQARPDS PAICAWDGEL TYRKLDELST RMSHSLLQLG AGFHKGLVPL CFDKSMWTAV
     AILGVLKAGV GFILLDPHLP EQRMRDIVDQ VGSKVIVTCP TREILCSRLA EATVAISWDY
     FSGQLDWTQQ ELPSVSPSST AYVVFTSGST GTPKGVVVTH ANAVSAQHHQ LEPMGHTPES
     RLFDFASYSF DVSISNIVSM LACGGCLCVP SESDRTDDME KSIVSLRVNA LDLTPSTLQL
     LSPERLPAVR QLTLGGEPLR EADVEKWCGK TRICNAYGPS ECTPTATINS NAMEPQMATH
     IGKGAGVVTW IVDADDHDEL LPLGCTGELL LEGPLVGRGY FNDSAKTAAA FIEDPKWLLR
     GSISHPGRQG RLYKTGDLVK YNRDGSLAFV GRKDTQVKVR GQRVEPGEIE AVLRSHESVD
     GAVVVFHRLT DQELWLAAFV TTREDDGKIP QSQSLAHDET QLKQKRIQAW EEEFEGETYL
     AIGATEAENI GRDFVGWSSM YDGSEINKVE MNEWLDDTIA TMLNGGPAGH VLEIGSGSGM
     MLFNLANHSL QSYIGVDPAM RAVDFTTKAA KSVPDLADKV NVFKGTAEDI MNLDMPIHSE
     LAVMNSVVQY FPSQDYLFNI IQHLASLGSI KTIFVGDIRS HALHKEFMAR RALHIAGKDA
     SREEFSGIME NLLKGEPELL VDPGFFTSLP HRIHGVTHVE ILPKRMKATN ELSSYRYAAV
     LHVNSHGEQA KDGRAQDIGA DEWIDYVSNG LDRQAVSGLL GTASRVAISN IPYSKTIYER
     EIVNAVEASK NIPKLERESE WLAAALQASQ EHSSLCAFDL AELAQLAGYR VECSWARQYS
     QRGGLDAVFY CGGSGTDSER RTLFRFPTDH EGRPCHVLST NPLEQQRKSK LRGDLEQLLR
     SKLPSYMVPQ AIKILDKMPV NHTGKIDRSM LSESLQQKAP PTARKRLPST APERAMQQIW
     SKVLSIESSQ IGLDDGFIKL GGNSLSAMKV VSMAREEGIR LEVADMFHHS TTSIAHLLQT
     AAAGVSESGA ALPGVTSDRL LSDLARYDCT IAMAQSEAAN KRLSATSHGG IRDTRLTVVL
     TGANGFIGTQ ILRQLLDHGR FSRVIAIVRG TSASKARQRA IDAAKNAQWW SEFYSSELEV
     WRGDLALPRL GLGKENWNTL ADGTVDVFIH NGASVHFMKS YSALQAANVE STAQVLRVAA
     ENPSMRVVYV SSARCCDPEL EREEDVAKAL ADRPNGYTTT KFIAEALVKR AAARGLGRRD
     QFAVVSPGLV VGTPTEGVAN ADDWLWRMTA ACIRVGVVNG EESDNWIPIA DAAATATTVI
     ETSLGRSSGI VTQVKGGLTM GEFWETLRAI GYTLRGEDSS TCMAAIRQDV EKNRDTHPLG
     ALSDMLQDLA DTARSQWADS WRTGGLSSPA RLKLALVKSA GFLSKVGVLP LPDGNDEPAQ
     ARENLRAFTR SGG