PYIC_MAGGR
ID PYIC_MAGGR Reviewed; 369 AA.
AC A0A4P8W733;
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=Trans-enoyl reductase pyiC {ECO:0000303|PubMed:31099577};
DE EC=1.-.-.- {ECO:0000305|PubMed:31099577};
DE AltName: Full=Pyrichalasin H biosynthesis cluster protein C {ECO:0000303|PubMed:31099577};
GN Name=pyiC {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: Trans-enoyl reductase; 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 (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 -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31099577}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- DISRUPTION PHENOTYPE: Results in the complete abolition of pyrichalasin
CC H and deacetylated pyrichalasin H production.
CC {ECO:0000269|PubMed:31099577}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; MK801691; QCS37515.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8W733; -.
DR SMR; A0A4P8W733; -.
DR Proteomes; UP000515153; Genome assembly.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..369
FT /note="Trans-enoyl reductase pyiC"
FT /id="PRO_0000449432"
FT BINDING 52..55
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 137..144
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 195..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 213
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 260..261
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 280..284
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 349..350
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 369 AA; 40287 MW; 7B36EF34DBA600AD CRC64;
MQTSNYGSLP TSRSAVVLGN DERLRIERHL PLPALRPNEV LVQVKAVAIN PCDYKMHQRF
PCPGAVDGCD FAGVIVGVGP EVLKFGLGDR VCGAVHGSNP LRPESGSFTD YMTSESEFTL
KIPAGLSFEQ AVGMGVTGIG TLGMALFRTL QLPGSLDRPA TKPRTVLVHG GSSSVGTMAI
QLLRLLGHVP IATCSPKNFA LARRFGAEEV FDYNSPDCAA AIKAYTKNTL SYILDPFTDA
KSVDLCYKAM GRAGGRYCCL EMYPEYVLQR KSIKVGFVMG PLLLGHRLAL SQGYERDEDP
EMRAFGVEWY KDVQKMLDRG LLKRHPIKLL GDSFEALIEG VEMLQRKEVS GEKLVVALDS
EQSKPVLTK
