LPSB_CLAPU
ID LPSB_CLAPU Reviewed; 1308 AA.
AC Q8J0L6;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=D-lysergyl-peptide-synthetase subunit 2 {ECO:0000303|PubMed:10071219};
DE Short=LPS2 {ECO:0000303|PubMed:10071219};
DE EC=2.3.1.- {ECO:0000269|PubMed:19139103};
DE AltName: Full=Ergot alkaloid synthesis protein ps2 {ECO:0000303|PubMed:14700635};
DE AltName: Full=Nonribosomal peptide synthetase 2 {ECO:0000303|PubMed:14700635};
GN Name=lpsB {ECO:0000303|PubMed:17720822};
GN Synonyms=cpps2 {ECO:0000303|PubMed:14700635};
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], FUNCTION, AND DOMAIN.
RC STRAIN=P1 / 1029/N5;
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 [2]
RP IDENTIFICATION IN THE EAS 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 [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.
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, 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, 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 [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: D-lysergyl-peptide-synthetase subunit 2; part of the gene
CC cluster 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 -!- 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). LpsB 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; AJ439610; CAD28788.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8J0L6; -.
DR SMR; Q8J0L6; -.
DR VEuPathDB; FungiDB:CPUR_04083; -.
DR BioCyc; MetaCyc:MON-17448; -.
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; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
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; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 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..1308
FT /note="D-lysergyl-peptide-synthetase subunit 2"
FT /id="PRO_0000439110"
FT DOMAIN 803..871
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 261..658
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 910..1299
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 835
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1308 AA; 143850 MW; 47551421976D299F CRC64;
MATPEKWRKY LEDYIPCSFP TFLDNEGADS KSFASVLVRL EHPYGRLMSF SNNCGVDVAV
VLNVAWGIVL QAYTGQDATC FAVIAESNLN IRPCRIRFTS DKVVSDILSA CQSPCSEKTG
DHDIPASHLS QDGGFLASEF FNTCIWGPMQ GSQMTSETQA ADMNRNALNL FDLVTRVEVP
RVEVDKSITR ITLTYKRGLM REHQALAVAK AMERAISEII SGKERLDQFC LLTSEDRRQM
SLWNMNLSDN SDARIETLIH EWCRRTPSAV AVCGWDGDFS YKELNELSTG VKHDLRHLGI
GPEVFVPILF EKSRWAVIAM LGVMKAGGAF ILLDPAHPPK RLRSICDKVS ARLVVSSVQQ
ADLAAGLAGH VVIVGGEVAT AGMAQHVGEH DDSMDCIAAP HNALYAVFTS GSTGTPKGVV
NSHSSFLAAM PVYLKALELD NNSRVFQFAS YAFDVTIFDA LMTLVAGGCV CVLSNADRSS
DLTSAIQHFG TTHLSVTPTV ARILDPQDFP SLKTIVLGGE LSASDELLKW VNNVRVIRLY
GASECTVMSI QCTSGPASSI KTINYETGNC CWVVNPQNHE QLRPLGAVGE LLVEGAVVGR
GYLDDASQTS ETFIEAPAWL QELRQGSSTV YKSGDLVRIA ADKSVQFVCR KSTQVKLRGQ
RIELGEVEHH VRLAIPSATE CVVELITIPD ASRPPMLMAF VLSDTDASTS SITARRNATS
DAVFAEPSAS FRSQIASITS KLRDALPSYM VPSVILPLRI MPLTGTDKIN RKLLRQLAAA
LSREDLQLYQ AQQTTYRAPS NDIEEAFQRF FAQALGLSLD QIGADDHFFS LGGDSLTAMR
LAAMARKAKF DLTVQNVFDH PELSELARHT KLVADESQEF PQPFTLIAGS KQGIVRDAAR
QCRLPSRVIE DVYPCTPLQK GLLAETMRDA AAFVAKIEVP LPRDVDLDRL RQAWAAVAKA
NPILRTRMIF SPSYGMLQVV VREDVPWIES DEVESQELVV VGRSLVQLIL RRRPSTALFL
HIHHAVYDGY SLPLMFAQLN NAYHGETLAF RPASAFIRYL ATMPDATDYW QSMCQGLESP
SFPALPHPSH RPHPDSKATH TVCVASPHAR EYTPNTHVRL AWAITQAHEQ GLLDVFYGTV
VSGRNAPVDQ IESMLIPTVA TVPCRITLDV DSPVRKILHR IQDVATRGIP FEQIGLAEIS
HLGKDAAHAC SFQTLLLMQP TAVEQNENDF FNTSTSDANY RADATYAINL FCTLENQDLS
VTALYDGNIV STDTMQRLLQ NLGKSMQEIH AAPRTLIGDI LKSLHSRL
