SIRC_LEPMC
ID SIRC_LEPMC Reviewed; 470 AA.
AC Q6Q881;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Cytochrome P450 monooxygenase sirC {ECO:0000303|PubMed:15387811};
DE EC=1.-.-.- {ECO:0000305|PubMed:15387811};
DE AltName: Full=Sirodesmin biosynthesis protein C {ECO:0000303|PubMed:15387811};
GN Name=sirC {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], AND FUNCTION.
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 FUNCTION, AND CATALYTIC ACTIVITY.
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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:15387811}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AY553235; AAS92547.1; -; Genomic_DNA.
DR AlphaFoldDB; Q6Q881; -.
DR SMR; Q6Q881; -.
DR PRIDE; Q6Q881; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 2.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 2.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..470
FT /note="Cytochrome P450 monooxygenase sirC"
FT /id="PRO_0000437706"
FT TRANSMEM 12..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 410
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 470 AA; 53860 MW; 20C9A1221D2B864E CRC64;
MESIVYETQP LLRGMVVGTI MLLCYRYGLA LSILQLYLNF MYRITNEKGK PLRGPEFSWP
DGQTVEKFLQ GGQKSFSWQA YGPLYRIWTV FRPEVVITRP EDVKAFFFDS HTHQKAASSN
AGWLFSQILG DCLGLINGER WSRVRHAFDP FFTRKISAQR LPHIMAAGEG YVNEVHQYDL
GGKQAASTIN LNAVDAFQRF PFFYVAEIIY GPLGITERVE LWKLAETHTN IFRRLVQGGI
HRYKATKFLS TSAYKETAHF VAAWRQFTLE LAQKQLREGR TSPLTDLMAE VEDGKVTLNE
VLHTIDESLF ANLDVTTHVL TWAIVLLGNH PDVQELVRSE IKANTNDLET YMNRKDTLLH
YSLLESLRVR PLLAFTIPES AQEDKVLSGY RVPKNIRYNL STFGFGPRKC LGQHMAENMI
KAILVPLLRQ FRFKLLADQY KNGEYKVDKT NWVTLSDVNL EMERVPSGGS
