ID   PYIA_MAGGR              Reviewed;         409 AA.
AC   A0A4P8WAD3;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   31-JUL-2019, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=O-methyltransferase pyiA {ECO:0000303|PubMed:31099577};
DE            EC=2.1.1.- {ECO:0000305|PubMed:31099577};
DE   AltName: Full=Pyrichalasin H biosynthesis cluster protein A {ECO:0000303|PubMed:31099577};
GN   Name=pyiA {ECO:0000303|PubMed:31099577};
OS   Magnaporthe grisea (Crabgrass-specific blast fungus) (Pyricularia grisea).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Magnaporthales; Pyriculariaceae; Pyricularia.
OX   NCBI_TaxID=148305;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RC   STRAIN=NI980;
RX   PubMed=31099577; DOI=10.1021/acs.orglett.9b01344;
RA   Wang C., Hantke V., Cox R.J., Skellam E.;
RT   "Targeted gene inactivations expose silent cytochalasans in Magnaporthe
RT   grisea NI980.";
RL   Org. Lett. 21:4163-4167(2019).
RN   [2]
RP   FUNCTION.
RX   PubMed=31644300; DOI=10.1021/acs.orglett.9b03372;
RA   Wang C., Becker K., Pfuetze S., Kuhnert E., Stadler M., Cox R.J.,
RA   Skellam E.;
RT   "Investigating the function of cryptic cytochalasan cytochrome P450
RT   monooxygenases using combinatorial biosynthesis.";
RL   Org. Lett. 21:8756-8760(2019).
RN   [3]
RP   FUNCTION.
RX   PubMed=32039410; DOI=10.1039/c9cc09590j;
RA   Hantke V., Skellam E.J., Cox R.J.;
RT   "Evidence for enzyme catalysed intramolecular [4+2] Diels-Alder cyclization
RT   during the biosynthesis of pyrichalasin H.";
RL   Chem. Commun. (Camb.) 56:2925-2928(2020).
CC   -!- FUNCTION: O-methyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of the mycotoxin pyrichalasin H, a tyrosine-derived
CC       cytochalasan that inhibits the growth of rice seedlings, but also
CC       inhibits lymphocyte capping and actin polymerization and alters cell
CC       morphology (PubMed:31099577) (Probable). Pyrichalasin H is indicated as
CC       the responsible agent for the genus-specific pathogenicity of M.grisea
CC       toward crabgrass (PubMed:31099577). The first step in the pathway is
CC       catalyzed by the O-methyltransferase pyiA which methylates free
CC       tyrosine to generate the precursor O-methyltyrosine (PubMed:31099577).
CC       The hybrid PKS-NRPS pyiS, assisted by the enoyl reductase pyiC, are
CC       responsible for fusion of the O-methyltyrosine precursor and the
CC       polyketide backbone (PubMed:31099577). The polyketide synthase module
CC       (PKS) of pyiS is responsible for the synthesis of the polyketide
CC       backbone and the downstream nonribosomal peptide synthetase (NRPS)
CC       amidates the carboxyl end of the polyketide with the O-methyltyrosine
CC       precursor (PubMed:31099577). As the NRPS A-domain demonstrates
CC       substrate tolerance, pyiS can also use phenylalanine, tyrosine and even
CC       para-chlorophenylalanine as amino acid precursor, which leads to the
CC       production of novel cytochalasans, including halogenated cytochalasans
CC       (PubMed:31099577). Because pyiS lacks a designated enoylreductase (ER)
CC       domain, the required activity is provided the enoyl reductase pyiC
CC       (PubMed:31099577). Reduction by the hydrolyase pyiE leads to 1,5-
CC       dihydropyrrolone, which is substrate for dehydration and intra-
CC       molecular Diels-Alder cyclization by the Diels-Alderase pyiF to yield
CC       the required isoindolone-fused macrocycle (PubMed:32039410). The
CC       tailoring cytochrome P450 monooxygenases piyD and piyG catalyze the
CC       hydroxylation at C-18 and C-7, respectivily, whereas the short-chain
CC       dehydrogenase/reductase pyiH reduces the carbonyl at C-21 in
CC       preparation for the transfer of an acetyl group by the
CC       acetyltransferase pyiB (PubMed:31099577). These 3 reactions whose order
CC       is not clear yet, lead to the production of O-methylpyrichalasin J, a
CC       deacetylated pyrichalasin H (PubMed:31099577). Finally, pyiB to
CC       converts O-methylpyrichalasin J into the final product pyrichalasin H
CC       via acetylation of C-21 (PubMed:31099577).
CC       {ECO:0000269|PubMed:31099577, ECO:0000269|PubMed:32039410,
CC       ECO:0000305|PubMed:31644300}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31099577}.
CC   -!- DISRUPTION PHENOTYPE: Leads to the loss of pyrichalasin H production,
CC       but accumulates the tyrosine and phenylalanine analogs of pyrichalasin
CC       H, called magnachalasin H and cytochalasin H.
CC       {ECO:0000269|PubMed:31099577}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. Cation-independent O-methyltransferase family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR   EMBL; MK801691; QCS37511.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A4P8WAD3; -.
DR   SMR; A0A4P8WAD3; -.
DR   Proteomes; UP000515153; Genome assembly.
DR   GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR016461; COMT-like.
DR   InterPro; IPR001077; O_MeTrfase_dom.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF00891; Methyltransf_2; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS51683; SAM_OMT_II; 1.
PE   3: Inferred from homology;
KW   Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW   Transferase.
FT   CHAIN           1..409
FT                   /note="O-methyltransferase pyiA"
FT                   /id="PRO_0000449451"
FT   REGION          1..46
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..43
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        317
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT   BINDING         271
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ   SEQUENCE   409 AA;  45694 MW;  9FB375240610AC9E CRC64;
     MASQDGTTEL LSQSVNSTCI PGSTYHVDRG RASSASTPPT SPPLSEVDYT PLLESTQEPR
     HEYTQLAHSL VKAMADYVGH LQEENLPMPS LEPAAQVHGG LKVQGGVAAR DTVVKLAQKI
     VAMTMDPEMK LFISSLQFHF CSSLKVAIDL RVHELDECFR ASSRQADALA LARYREPHEA
     DTLGFGLAFN TTANFWEVLA RDTEGKRSQR FNRAMRAVNI NALEVIPRIY PFNRIGGNGL
     LVDVGGGLGQ VARAIMATNQ GSRLQRCIVQ DVCAADDVLE EVLESNRKLG VELQRHDFFD
     KQPVTGASIY FFRHIFHDWP DRACVKILKQ IVQAMGRDSR LLICDQVVDD EPSIPATLYD
     IDMWTLFGGK ERNRSEWEAL FRAADERLYI KKVWTTTEAP TTILEVCLW