PYIE_MAGGR
ID PYIE_MAGGR Reviewed; 463 AA.
AC A0A4P8W7Y2;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 25-MAY-2022, entry version 9.
DE RecName: Full=Hydrolase pyiE {ECO:0000303|PubMed:31099577};
DE EC=3.7.1.- {ECO:0000305|PubMed:32039410};
DE AltName: Full=Pyrichalasin H biosynthesis cluster protein E {ECO:0000303|PubMed:31099577};
GN Name=pyiE {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, AND 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: Hydrolyase; part of the gene cluster that mediates the
CC 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:32039410}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q93NG6}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC family. {ECO:0000305}.
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DR EMBL; MK801691; QCS37512.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8W7Y2; -.
DR SMR; A0A4P8W7Y2; -.
DR ESTHER; maggr-pyie; Duf_1100-S.
DR Proteomes; UP000515153; Genome assembly.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF12697; Abhydrolase_6; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 3: Inferred from homology;
KW Hydrolase; Reference proteome.
FT CHAIN 1..463
FT /note="Hydrolase pyiE"
FT /id="PRO_0000449475"
FT REGION 350..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 252
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q4WZB3"
SQ SEQUENCE 463 AA; 50233 MW; EE54BC55DE21E89B CRC64;
MHKFFPRSGF FDFETVRILG TACYGGADVA EVLEAVGEIK SDDAASWEEA WRRQSWWAEA
LADQAREGGD REAARRAYLR ASNYARASGY MYVSDLGAEG GNAPPTQDPR ALPVAEKVGR
LFRKALALME GEVRALSIPC GAQALPGLLY LPPPGKRIPG RDKIPVLVFL GGADSCQEEL
YYLYPAAGPG LGYAVLTFDG PGQGIVLRKH GLRVRPDWEV VTSSVLDYLE AYSAQHPGLE
LDMKAIAVSG ASMGGYYALR SAVDRRVKAC VSIDPFYDMW DFGTAHVSPL FISAWTSGII
SSGFVDKLMT VVSRLWFQMK WEIALTGTLF GLSSPSQILL NMKNYTLSGK SDGSRANGKK
SHSPTDGGGV ESDSFLSEVR CPVFLSGAGK SLYLDVDSHT RRCYDGLTGV AAKDKELWVP
ESEGQGSLQA KMGALALCNQ KTFQFLDKVL GVQRVPLDVS AHI
