PYIG_MAGGR
ID PYIG_MAGGR Reviewed; 504 AA.
AC A0A4V1FW34;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Pyrichalasin C-7 hydroxylase {ECO:0000303|PubMed:31099577};
DE EC=1.-.-.- {ECO:0000305|PubMed:31099577};
DE AltName: Full=Cytochrome P450 monooxygenase pyiG {ECO:0000303|PubMed:31099577};
DE AltName: Full=Pyrichalasin H biosynthesis cluster protein G {ECO:0000303|PubMed:31099577};
DE Flags: Precursor;
GN Name=pyiG {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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxin pyrichalasin H, a tyrosine-
CC derived cytochalasan that inhibits the growth of rice seedlings, but
CC also inhibits lymphocyte capping and actin polymerization and alters
CC cell morphology (PubMed:31099577) (Probable). Pyrichalasin H is
CC indicated as the responsible agent for the genus-specific pathogenicity
CC of M.grisea toward crabgrass (PubMed:31099577). The first step in the
CC pathway is catalyzed by the O-methyltransferase pyiA which methylates
CC free tyrosine to generate the precursor O-methyltyrosine
CC (PubMed:31099577). The hybrid PKS-NRPS pyiS, assisted by the enoyl
CC reductase pyiC, are responsible for fusion of the O-methyltyrosine
CC precursor and the polyketide backbone (PubMed:31099577). The polyketide
CC synthase module (PKS) of pyiS is responsible for the synthesis of the
CC polyketide backbone and the downstream nonribosomal peptide synthetase
CC (NRPS) amidates the carboxyl end of the polyketide with the O-
CC methyltyrosine precursor (PubMed:31099577). As the NRPS A-domain
CC demonstrates substrate tolerance, pyiS can also use phenylalanine,
CC tyrosine and even para-chlorophenylalanine as amino acid precursor,
CC which leads to the production of novel cytochalasans, including
CC halogenated cytochalasans (PubMed:31099577). Because pyiS lacks a
CC designated enoylreductase (ER) domain, the required activity is
CC provided the enoyl reductase pyiC (PubMed:31099577). Reduction by the
CC hydrolyase pyiE leads to 1,5-dihydropyrrolone, which is substrate for
CC dehydration and intra-molecular Diels-Alder cyclization by the Diels-
CC Alderase pyiF to yield the required isoindolone-fused macrocycle
CC (PubMed:32039410). The tailoring cytochrome P450 monooxygenases piyD
CC and piyG catalyze the hydroxylation at C-18 and C-7, respectivily,
CC whereas the short-chain dehydrogenase/reductase pyiH reduces the
CC carbonyl at C-21 in preparation for the transfer of an acetyl group by
CC the acetyltransferase pyiB (PubMed:31099577). These 3 reactions whose
CC order is not clear yet, lead to the production of O-methylpyrichalasin
CC J, a 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:31099577}.
CC -!- DISRUPTION PHENOTYPE: Leads to the loss of pyrichalasin H production,
CC but accumulates novel cytochalasans, all lacking a hydroxyl group at C-
CC 7. {ECO:0000269|PubMed:31099577}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK801691; QCS37514.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4V1FW34; -.
DR SMR; A0A4V1FW34; -.
DR Proteomes; UP000515153; Genome assembly.
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; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..504
FT /note="Pyrichalasin C-7 hydroxylase"
FT /id="PRO_0000449435"
FT BINDING 449
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"
SQ SEQUENCE 504 AA; 57662 MW; 647784166A085A71 CRC64;
MLNSAACIVL AITAVLGRMI YTHFYSNTCA AMKRALAHIP ELHFEEDDTP ERYRTETRSL
VRKGYERYLQ YGIPFQMRNP VSELGNQVVL PVKYLEEVKR APRSLYSFEA FSEKVFLLKY
IDAPRQTDAL LYAVKLDINK NMDHILNGLW DETQVLLKET VPVTGQITIP GGELACNIIA
RTMSYVLVGP SLCRNPEWTK IAIEATFALV AGTQGLRDRY SPGWRWLARF QRSSEKLGEV
REKAMELIKP LHEERMKALK DDSGQFRNFY DTIFWTMNKR KVDRSLRAIV DQQLFLTLAS
IHTTAGTLQS ILCDWLAHPE YHDEILAEIN ERLAAFKGAG GKWTQQEVNE MKKLDSFMKE
STRVNPVGCM TVQRYAQRTH TFSDGFVLPA GTIFQFPSDA VHHDPKLFPD PEKFDGHRFL
RLREKDANAY HYGYVSDTTL NWGAGTHACP GRFLATYVLK FAFIALITQY DLSFPEGTGK
PGYFYFDNSV RIDPTAKLDI KKSS
