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 02-DEC-2020, entry version 8. 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). 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, followed by CC dehydration and intra-molecular Diels-Alder cyclization by the Diels- CC Alderase pyiF then yield the required isoindolone-fused macrocycle CC (Probable). The tailoring cytochrome P450 monooxygenases piyD and piyG CC catalyze the hydroxylation at C-18 and C-7, respectivily, whereas the CC short-chain dehydrogenase/reductase pyiH reduces the carbonyl at C-21 CC in 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:0000305|PubMed:31099577, 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}. 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; MK801691; QCS37511.1; -; Genomic_DNA. DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR InterPro; IPR016461; COMT-like. DR InterPro; IPR001077; O_MeTrfase_dom. DR InterPro; IPR029063; SAM-dependent_MTases. 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; S-adenosyl-L-methionine; Transferase. FT CHAIN 1..409 FT /note="O-methyltransferase pyiA" FT /id="PRO_0000449451" FT ACT_SITE 317 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020" FT BINDING 271 FT /note="S-adenosyl-L-methionine" 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 //