ID   TCPP_CLAP2              Reviewed;        2049 AA.
AC   M1WCQ3;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2013, sequence version 1.
DT   25-MAY-2022, entry version 34.
DE   RecName: Full=Nonribosomal peptide synthetase tcpP {ECO:0000303|PubMed:27390873};
DE            Short=NRPS tcpP {ECO:0000305};
DE            EC=6.3.2.- {ECO:0000305|PubMed:27390873};
DE   AltName: Full=Thioclapurine biosynthesis protein P {ECO:0000303|PubMed:27390873};
GN   Name=tcpP {ECO:0000303|PubMed:27390873}; ORFNames=CPUR_02680;
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 [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   [2]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=27390873; DOI=10.1371/journal.pone.0158945;
RA   Dopstadt J., Neubauer L., Tudzynski P., Humpf H.U.;
RT   "The epipolythiodiketopiperazine gene cluster in Claviceps purpurea:
RT   dysfunctional cytochrome P450 enzyme prevents formation of the previously
RT   unknown clapurines.";
RL   PLoS ONE 11:E0158945-E0158945(2016).
CC   -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC       that mediates the biosynthesis of an unusual class of
CC       epipolythiodioxopiperazines (ETPs) lacking the reactive thiol group
CC       important for toxicity (PubMed:27390873). Firstly, L-tyrosine is
CC       prenylated by tcpD, before undergoing condensation with L-glycine in a
CC       reaction catalyzed by the NRPS tcpP leading to the diketopiperazine
CC       (DKP) backbone (PubMed:27390873). Afterwards the alpha-carbon of
CC       tyrosine is oxidized by the cytochrome P450 tcpC to form a hydroxyl
CC       group (PubMed:27390873). However, in contrast other ETP biosynthesis
CC       pathways studied so far, tcpC is not able to bishydroxylate the DKP at
CC       both alpha-carbon positions, but hydroxylates the alpha-carbon of the
CC       tyrosine part and the nitrogen of the glycine part (PubMed:27390873).
CC       The next steps involve an alpha,beta-elimination reaction catalyzed by
CC       tcpI, a methylation by the methyltransferase tcpN the action of the
CC       four enzyme cascade tcpG/K/J/I (PubMed:27390873). Due to a
CC       dysfunctional cytochrome P450 monooxygenase tcpC, the pathway leads to
CC       the biosynthesis of probable non-toxic metabolites lacking the reactive
CC       thiol group (PubMed:27390873). {ECO:0000269|PubMed:27390873}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:27390873}.
CC   -!- INDUCTION: Expression is positively regulated by the thioclapurine
CC       cluster-specific transcription factor tcpZ (PubMed:27390873).
CC       {ECO:0000269|PubMed:27390873}.
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, epimerase (E) domains
CC       (responsible for L- to D-amino acid conversion) are present within the
CC       NRP synthetase (By similarity). NRPS10 has the foolowing architecture:
CC       A-T-C-A-T-C (PubMed:27390873). {ECO:0000250|UniProtKB:Q4WMJ7,
CC       ECO:0000305|PubMed:27390873}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; CAGA01000011; CCE28989.1; -; Genomic_DNA.
DR   AlphaFoldDB; M1WCQ3; -.
DR   SMR; M1WCQ3; -.
DR   STRING; 1111077.M1WCQ3; -.
DR   PRIDE; M1WCQ3; -.
DR   EnsemblFungi; CCE28989; CCE28989; CPUR_02680.
DR   VEuPathDB; FungiDB:CPUR_02680; -.
DR   eggNOG; KOG1176; Eukaryota.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_0_5_1; -.
DR   OrthoDB; 4243at2759; -.
DR   Proteomes; UP000016801; Unassembled WGS sequence.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 2.
DR   Gene3D; 3.30.559.10; -; 2.
DR   Gene3D; 3.40.50.12780; -; 2.
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; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE   2: Evidence at transcript level;
KW   Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW   Repeat.
FT   CHAIN           1..2049
FT                   /note="Nonribosomal peptide synthetase tcpP"
FT                   /id="PRO_0000437701"
FT   DOMAIN          497..573
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1550..1625
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          13..395
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          605..913
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          1071..1452
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255"
FT   REGION          1662..2044
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         534
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1585
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2049 AA;  226754 MW;  01A3E7289AD4E694 CRC64;
     MATVPVSVHD LIRHHAEAHP EALAISKNED QITYGELYAA STRIAQLLAD QGVEKGDVVP
     LLGSRCLEMI ACTLAIFMIG ATLVPMEAGS WSEARIQTVL DALEYKTLLV TADGDVRRRK
     TIDYHEIQRA MTGGNGWDCG NAKVPINGPE SVRDVAYIIF TSGTTGNPKG VKVTHQSLLN
     YVWPAHANAP FNLGVGPSDT SLLLFSVAFD AFYGVLLSTL CNGGHVLLSE PSTFIDDAKK
     CTLLPATPTL LGTISDVSPY SNVRGIFLGG ETPTPDVVRK WWTPSRSMWN AYGPTETTVS
     VTMAELRPDV PIVLGEPIRN SKIIILDSNL EEATQGEICV LGSTVLALGY YKNQAQTDDK
     FVLWNNERIY RTGDMAKWTE NGLKFLGRKD QLIKNRGFLI NLEADVIPAI LSQNNVETAT
     VLMHRQRLIA FVTPLTVNGD LVRQEMARRF DQFLVPDEIQ SRDQLPQTIN GKVDNRALYD
     ELVQRDTVGV ASNAPIATAD TKLSALMNTM SEALTIPAQM IRPELSFTDV GGNSLLAIKM
     LSALRQKGLS LSMSSLFLLP TISEISNHII EFDASVSHDD DDQQAADLAG CGKSLSLPGA
     TRSAREITMT DVQRGMIRST LHDAPTGYML ITISLHQNAR DIHPSRLSNA VSQVLGRHDI
     FCSSFDLVRG TISVNDRYQH DWETRALDGS PMSQAIADES ELLNQRARMS DTSNEFFRPV
     NAFRLLLGEN SESVLLWLVH HALVDGWSVG KLLNDFRAQL LTEHSQAAQQ SQFSQYTAAL
     TPHLEKVHEP AELFWRESMA GLLDGTELKV GRLEDGASNG SRIEHECLSL GLSLEQTEIA
     ARALGFSPAV IFHAAWALLL SSYASEDAVV FGSVFSARSF HVPRIEEIVG PLINLCPFPV
     QVHALGSKMD LLSSVQSLLL QISEYQWSAS KILQDIASGS HARIFSTALF LEYDLPLYAS
     SDQHELAAWT YDRKDWPEFG LTLQVQCVGE HLGFRAVIKD PKYESPLASR LLGHFRNLCL
     FLLSPKISTL AEANDSMLEP TEMLCLTRTS TSLFTPYSGP PTLKQAFEIG VAAWPMSVAL
     ESLSGKLLYQ ELDDITNALA CSIRGLIRPR DVVALLSDGS QNWLLGVISI IKAGATYLPL
     DTKLPAQRME AMMETSGACL CVYPNASSLA AFSDLSKPRY LVYEHAAVKT MNGSSSDRLE
     DIVGPDDYAY IMFTSGSTGT PKGIRVTHRA TTSHLSFEPA RLHARPGRRH AQVFSPGFDV
     NIAEIFGTLC YGATLVLKDP ADPFAHLSRV DAAMITPSFL SVLSPTELQN LDSIYLIGEA
     VSQSLADRWS PGRVLYNFYG PCECTIAVAY TRLEIGRPVT LGKTIPRVGC YILDRLLRPV
     PMGVIGEICL YGVQTMEGYI GQNADEVTKR AFVQDPFRRP GERMYRTGDL AFWTENMEMR
     YVGRADHQVK VRGYRIELEE IENVIRRSDE NVSQSVAIVH QDTIYAFATP QGARIDQIQQ
     CLRQHLPSYA VPQLIIALEA FPTTPNQKLD RKALINLLAP VCSRENETTD HTELVVSQVW
     REVIGLDEEI ALSIDDDFLA IGGNSLRQIA AAQKICSKLG CRVPLSLFIT SRSIRSLAAS
     VKKHLAQQSL ASTTSVSLAE FSNQCQFLSS KLSYLEKEFL RMHKQASNPS SFNVVHRVRL
     QGDVDSLLLE RALRTVVSKH DILRASYVEV DGVPQRVIQT NTIQIDRIEC SDDVAKLHDY
     ISTKFELSGV LIRIALVERC GATDVVLVQH HIITDQVSVQ IFLTNLSMEY RALACRDESG
     QTICTSDHST NDYHVWALWR DSQLEQPPEN THCEFWRSQF GEKTESIRLV QHQKHPAGEF
     HSVPRRLKRN SSSGSIEVYL AAAALALQKV SRLNTIRLGV PFLDRLEPGT ENMMGVFLDA
     LPVCVQIEPH TDLPSLLSTI RTTLTSALAH AIPSFMIKDI VGLDSIFEVM IVYNRFEDRV
     TRNMSIPGVS ISVEAMRAQG AKFPLLIEFN EHVDHVTLEI EYSEDVLTPS SLSRFEQEIC
     NLLDPQIVV