ID   SIRM_LEPMC              Reviewed;         414 AA.
AC   Q6Q880;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=O-methyltransferase sirM {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000255|PROSITE-ProRule:PRU01020};
DE   AltName: Full=Sirodesmin biosynthesis protein M {ECO:0000303|PubMed:15387811};
GN   Name=sirM {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.
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: O-methyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of sirodesmin PL, an epipolythiodioxopiperazine (ETP)
CC       characterized by a disulfide bridged cyclic dipeptide and that acts as
CC       a phytotoxin which is involved in the blackleg didease of canola
CC       (PubMed:15387811, PubMed:18272357, PubMed:19762440). SirD catalyzes the
CC       O-prenylation of L-tyrosine (L-Tyr) in the presence of dimethylallyl
CC       diphosphate (DMAPP) to yield 4-O-dimethylallyl-L-Tyr, and therefore
CC       represents probably the first pathway-specific enzyme in the
CC       biosynthesis of sirodesmin PL (PubMed:19762440, PubMed:21038099,
CC       PubMed:24083562). 4-O-dimethylallyl-L-Tyr, then undergoes condensation
CC       with L-Ser in a reaction catalyzed by the non-ribosomal peptide
CC       synthase sirP to form the diketopiperazine (DKP) backbone
CC       (PubMed:18272357). Further bishydroxylation of the DKP performed by the
CC       cytochrome P450 monooxygenase sirC leads to the production of the
CC       intermediate phomamide (PubMed:27390873). This step is essential to
CC       form the reactive thiol group required for toxicity of sirodesmin PL
CC       (PubMed:27390873). The next steps of sirodesmin biosynthesis are not
CC       well understood yet, but some predictions could be made from
CC       intermediate compounds identification (PubMed:18272357). Phomamide is
CC       converted into phomalizarine via oxidation, probably by sirT
CC       (PubMed:18272357). Further oxidation, methylation (by sirM or sirN) and
CC       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   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. Cation-independent O-methyltransferase family. COMT
CC       subfamily. {ECO:0000255|PROSITE-ProRule:PRU01020}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY553235; AAS92548.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q6Q880; -.
DR   SMR; Q6Q880; -.
DR   OMA; MMMTANG; -.
DR   GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.10; -; 1.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR031725; ASMT_dimerisation.
DR   InterPro; IPR016461; COMT-like.
DR   InterPro; IPR001077; O_MeTrfase_dom.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   Pfam; PF16864; Dimerisation2; 1.
DR   Pfam; PF00891; Methyltransf_2; 1.
DR   SUPFAM; SSF46785; SSF46785; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS51683; SAM_OMT_II; 1.
PE   3: Inferred from homology;
KW   Methyltransferase; S-adenosyl-L-methionine; Transferase; Virulence.
FT   CHAIN           1..414
FT                   /note="O-methyltransferase sirM"
FT                   /id="PRO_0000437723"
FT   ACT_SITE        321
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT   BINDING         270
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ   SEQUENCE   414 AA;  46556 MW;  74A882574C169386 CRC64;
     MDNELDNLIS LLQKSKASLK EKHGDRIRSI FAAHHSGSIL PKEDKSLYDK CLATVDLLDE
     VQQMLTPPLH TLIDGFFGFI NSKTLLCAVE FGIPDALSQG PKSIEQLASS SPQGELSPHR
     LTQVLRTLTG IGIFNYDKTS KLYSNNATSD LITTAHWSKW VYWTKFYPTE FYDMMRFLPD
     HIKANASRTA AQSNYNTDME FYEYLSNSGL AKEFHRVLGA GATAQLPGMI SDFPWDTLGD
     ETVLDLGTGS GEFLFQLLEN YPRMRGAFMD IPSTISRIQA ECEQPGGRFS GVRDRVAGFH
     AGNFLDEVPA SVVYTIKWCL HNWSDEDTIK ILQNIRRAIV VKPEARLLII ESVLEDGRTG
     RPARYGDIIM MATCNGKERD IENWQAVCEQ SGWEVVKSWA LRNSIPSCLE LRPI