SIRP_LEPMC
ID SIRP_LEPMC Reviewed; 2176 AA.
AC Q6Q883;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=Nonribosomal peptide synthetase sirP {ECO:0000303|PubMed:15387811};
DE Short=NRPS sirP {ECO:0000305};
DE EC=6.3.2.- {ECO:0000305|PubMed:15387811};
DE AltName: Full=Sirodesmin biosynthesis protein P {ECO:0000303|PubMed:15387811};
GN Name=sirP {ECO:0000303|PubMed:15387811};
OS Leptosphaeria maculans (Blackleg fungus) (Phoma lingam).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Leptosphaeriaceae;
OC Leptosphaeria; Leptosphaeria maculans species complex.
OX NCBI_TaxID=5022;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP INDUCTION.
RX PubMed=15387811; DOI=10.1111/j.1365-2958.2004.04215.x;
RA Gardiner D.M., Cozijnsen A.J., Wilson L.M., Pedras M.S., Howlett B.J.;
RT "The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus
RT Leptosphaeria maculans.";
RL Mol. Microbiol. 53:1307-1318(2004).
RN [2]
RP FUNCTION.
RX PubMed=18272357; DOI=10.1016/j.mycres.2007.08.017;
RA Fox E.M., Howlett B.J.;
RT "Biosynthetic gene clusters for epipolythiodioxopiperazines in filamentous
RT fungi.";
RL Mycol. Res. 112:162-169(2008).
RN [3]
RP FUNCTION.
RX PubMed=19762440; DOI=10.1099/mic.0.033886-0;
RA Kremer A., Li S.M.;
RT "A tyrosine O-prenyltransferase catalyses the first pathway-specific step
RT in the biosynthesis of sirodesmin PL.";
RL Microbiology 156:278-286(2010).
RN [4]
RP FUNCTION.
RX PubMed=21038099; DOI=10.1007/s00253-010-2956-x;
RA Zou H.X., Xie X., Zheng X.D., Li S.M.;
RT "The tyrosine O-prenyltransferase SirD catalyzes O-, N-, and C-
RT prenylations.";
RL Appl. Microbiol. Biotechnol. 89:1443-1451(2011).
RN [5]
RP FUNCTION.
RX PubMed=24083562; DOI=10.1021/cb400691z;
RA Rudolf J.D., Poulter C.D.;
RT "Tyrosine O-prenyltransferase SirD catalyzes S-, C-, and N-prenylations on
RT tyrosine and tryptophan derivatives.";
RL ACS Chem. Biol. 8:2707-2714(2013).
RN [6]
RP DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=20507539; DOI=10.1111/j.1364-3703.2007.00433.x;
RA Elliott C.E., Gardiner D.M., Thomas G., Cozijnsen A., Van de Wouw A.,
RA Howlett B.J.;
RT "Production of the toxin sirodesmin PL by Leptosphaeria maculans during
RT infection of Brassica napus.";
RL Mol. Plant Pathol. 8:791-802(2007).
RN [7]
RP FUNCTION.
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 sirodesmin PL, an
CC epipolythiodioxopiperazine (ETP) characterized by a disulfide bridged
CC cyclic dipeptide and that acts as a phytotoxin which is involved in the
CC blackleg didease of canola (PubMed:15387811, PubMed:18272357,
CC PubMed:19762440). SirD catalyzes the O-prenylation of L-tyrosine (L-
CC Tyr) in the presence of dimethylallyl diphosphate (DMAPP) to yield 4-O-
CC dimethylallyl-L-Tyr, and therefore represents probably the first
CC pathway-specific enzyme in the biosynthesis of sirodesmin PL
CC (PubMed:19762440, PubMed:21038099, PubMed:24083562). 4-O-dimethylallyl-
CC L-Tyr, then undergoes condensation with L-Ser in a reaction catalyzed
CC by the non-ribosomal peptide synthase sirP to form the diketopiperazine
CC (DKP) backbone (PubMed:18272357). Further bishydroxylation of the DKP
CC performed by the cytochrome P450 monooxygenase sirC leads to the
CC production of the intermediate phomamide (PubMed:27390873). This step
CC is essential to form the reactive thiol group required for toxicity of
CC sirodesmin PL (PubMed:27390873). The next steps of sirodesmin
CC biosynthesis are not well understood yet, but some predictions could be
CC made from intermediate compounds identification (PubMed:18272357).
CC Phomamide is converted into phomalizarine via oxidation, probably by
CC sirT (PubMed:18272357). Further oxidation, methylation (by sirM or
CC sirN) and reduction steps convert phomalizarine to deacetyl sirodesmin
CC (PubMed:18272357). Finally, acetyltransferase sirH probably acetylates
CC deacetyl sirodesmin to produce sirodesmin PL (PubMed:18272357).
CC {ECO:0000269|PubMed:19762440, ECO:0000269|PubMed:21038099,
CC ECO:0000269|PubMed:24083562, ECO:0000269|PubMed:27390873,
CC ECO:0000305|PubMed:15387811, ECO:0000305|PubMed:18272357}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:15387811}.
CC -!- INDUCTION: Expressed during canola infection (PubMed:20507539).
CC Expression is co-regulated with the other genes from the sirodesmin
CC cluster and corresponds with sirodesmin production (PubMed:15387811).
CC {ECO:0000269|PubMed:15387811, ECO:0000269|PubMed:20507539}.
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:15387811). {ECO:0000250|UniProtKB:Q4WMJ7,
CC ECO:0000305|PubMed:15387811}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of sirodesmin PL
CC (PubMed:15387811, PubMed:20507539). Decreases the number of lesions and
CC the efficiency in colonizing stems during infection of canola
CC (PubMed:20507539). {ECO:0000269|PubMed:15387811,
CC ECO:0000269|PubMed:20507539}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; AY553235; AAS92545.1; -; Genomic_DNA.
DR AlphaFoldDB; Q6Q883; -.
DR SMR; Q6Q883; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.30.559.10; -; 2.
DR Gene3D; 3.40.50.12780; -; 2.
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; 2.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 3.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 2: Evidence at transcript level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Repeat; Virulence.
FT CHAIN 1..2176
FT /note="Nonribosomal peptide synthetase sirP"
FT /id="PRO_0000437700"
FT DOMAIN 534..610
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1570..1646
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2106..2176
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 16..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..434
FT /note="Adenylation 1"
FT /evidence="ECO:0000255"
FT REGION 643..1073
FT /note="Condensation 1"
FT /evidence="ECO:0000255"
FT REGION 1094..1474
FT /note="Adenylation 2"
FT /evidence="ECO:0000255"
FT REGION 1661..2070
FT /note="Condensation 2"
FT /evidence="ECO:0000255"
FT MOD_RES 571
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1606
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2140
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2176 AA; 241505 MW; E86AA7AD4D5136D8 CRC64;
MHITKDIDTI FHRSLEGLTG DDHSPESRRD FPMSQSSGCR NGTDATVCHI FERIASQFPE
SVAAEDGGRN ITYGELHYAS NHLANHLSQI GIQSGQKIVI ISNRSLEMIV ALLGIMKSGA
CVVPIDFETW SQDRIQTTLE TTQCRYAIST KCIEIPNQEL ILFQEGDLQH VLDNRRDQPA
SFSTRGFQLP SADDLAYTIF TSGTTSKPKG VMVPHSAIAH YVQQVSDEAP FNLNVQASSR
VLLVFSVAFD ACLGVVLSTI CNGGTLILAT SMNFATVATT CTILPLTPTI LSTLRPGAEY
DSIKSIFLGG ESPSPNLLRP WLNGERRIFN CYGPTETTCT SLIKEVLPDE PNHLRYTVAG
SSVVLLDGNL REVSEGEIAI SGPGLAVGYF NNQALTAEKF IVYKGVRHYL TGDYGRKTSF
GIDFLGRKDR VVKNRGFLIN LEAEVEAVIT NMKLANSAAA LMHEGRLIMF VTPETIDVSS
LRSRLLEIRD SFLVPDRIYA ICSFPITSNG KVDLASLRQL LQEEKFTGVA THQSSPSSNL
YVVLEGFSKV LGLPPSALCG SSSFLDNGGN SLSAVSLASH LRERGLSITV REIFESDTAQ
RICDTLSATI LSTSDSEEAD LESLRENVVR AGYPLTPRME VAYMTAIQVN MIQSTIKMPS
MNYIQLSITF DLSSGLFKPE VFRRAWEIIV QRHSILRATF IPALEATVIA ADPTMDWREQ
LVDSSEWDSA VADAREKILC SMAPLDAEYL KPRSIFRLIT EPKSRTEFIW TIHHSLVDGW
SIAVIMRDLQ CILSQEELPK VAQFTSVATV QKALAQRSLS RGKQQSWEEK MQNYIPAPRL
RLPKPQGWAR AARAERRQLL GVHRSQVQRF VQEYRVSDAS IFLASWALVL SKYLSTDRVL
FGVVLSGRNL PMAAVDQVVG PLLDTVPFPV NTTSTQSTAE FLRTIHGTLH EMNESPWEMK
LQKSSMGPES LETLVALQYD LPDSTWNVDP KTWPSPQSMK HNETTELPLH ILIDMQNGGD
LEARYLYDCS HFEAAMIDQM LSHFSNMLKA ILMHPTVELV KSSMMNQLEI NDLLYSSPHM
HDAYDGPQSL KQAFEEVVDT WPDAIAVESV SDSISYKELD HRSSAISNAL LPLVGPGQIV
GILSDGSVSW ITAILAVLKA GAAYCPIDIA LPEERIKVML RESRCSLLLC TTEDLCELWA
NHSDLTCFSI GRLLSETLQT PERLPERCSP HDPAAVIFTS GSTGVPKGIL LEHIGILSLL
DFPNARLRSG PGRRNAQFLS LGFDCCVNEV FATLCYGATL VLRDPLDPVQ HIKRVHATMC
TPSFLATLDV NDFPNLELIA LAGEPVPQKL VDTWGHNRVL LNVYSPSECT ISTVYPQLYP
GVQVTLGSPV PRQAIYILDK DLNPVPVGVP GEICISGIQV TRGYLNRPEE TLVKFLPNPF
QKGWRLYRSG DLGRLTNSHE IEYIGRIDNQ VKVRGFRIEL EEIESTIAAL NPEVRQAAVI
VVNDVLIGFV TPSSLDTLAI QAIISRHLPS YCRPSYFVAL DNMPMSSNQK IDRKKLVSMK
AERNHFTKVP IEGTTERIIQ EIWKDLIPEL GEVSALDNFL QIGGHSLLQA RLTRQLGMAL
GNRIPLRIVI QNPVLRDLAL AIDKHILDGG SEDISRGQPE QNTVLSHLEE EMYTVHMLSS
EPSAWNIPYI ARLTGPLNLA AFEASWNNII RSNSILRARY QIKDGILTRS ISTSISPVTR
RYCKVTDDAL LDIVNRAFDL ANDQPIRLDL CLDRPTMSYV VLNMSHMIGD RSTMGEILRL
LEEEYAQMIL NDNFNLHEPL SESLPYSVWT AMRRKREVDA GLTHVLQKSL NPSLINPPLF
GTFKQELACS AHRDKRIEGD LFSSLKNLRG RFKASGHQLA IAAIGLTLHR LSHREDFIIA
APIEDRTEAG TENMFGLFLD RLLIPLRFNL HSPHSADDLI HMVKSASEQA MANYIPFADL
KNVLGMVGKS HSLCEIMVTY HASDLQGPNL TGVDALGIPV QPKGVKFPLM LEFSEFPESI
GIDLAYDSHA IDNATMDEFE VQLMAAFRYL ADETCSSTCT TYPPRLFPLI WSQKDTNTVA
PISEDQEMID LVREAMAECV GLNRCDISCS RSFFELGGSS VDCLRLQDRL IKSGVSVSLS
SIIHLQTAEL IAGAVE
