ID   PYTE_ASPTE              Reviewed;         263 AA.
AC   P9WEZ2; A0A5M3YUD2;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Reductase pytE {ECO:0000303|PubMed:32077283};
DE            EC=1.-.-.- {ECO:0000305|PubMed:32077283};
DE   AltName: Full=Pyranterreones biosynthesis cluster protein E {ECO:0000303|PubMed:32077283};
GN   Name=pytE {ECO:0000303|PubMed:32077283};
GN   ORFNames=ATETN484_0003083400, g7169;
OS   Aspergillus terreus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=33178;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=TN-484;
RA   Kanamasa S., Takahashi H.;
RT   "Aspergillus terreus TN-484 whole genome shotgun sequence.";
RL   Submitted (OCT-2019) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, DISRUPTION
RP   PHENOTYPE, AND PATHWAY.
RC   STRAIN=MEFC01;
RX   PubMed=32077283; DOI=10.1021/acs.jnatprod.9b01140;
RA   Tang S., Zhang W., Li Z., Li H., Geng C., Huang X., Lu X.;
RT   "Discovery and characterization of a PKS-NRPS hybrid in Aspergillus terreus
RT   by genome mining.";
RL   J. Nat. Prod. 83:473-480(2020).
CC   -!- FUNCTION: Reductase; part of the gene cluster that mediates the
CC       biosynthesis of pyranterreones, a family of antioxidative compounds
CC       (PubMed:32077283). The first step of pyranonigrins biosynthesis is
CC       performed by the hybrid PKS-NRPS synthetase pytA that condenses 4
CC       malonyl-CoA units ato the acetyl starter unit by the modular PKS of
CC       pytA (PubMed:32077283). The acyl chain is then connected to an L-serine
CC       through the amide bond by the modular NRPS of pytA (PubMed:32077283). A
CC       tetramic acid is formed and released from the PKS-NRPS pytA to give
CC       pyranterreone 5 with the help of the thioesterase pytI
CC       (PubMed:32077283). Pyranterreone 5 could be methylated by pytC to
CC       afford pyranterreone 6 (Probable). Both pyranterreones 5 and 6 are
CC       subsequently oxidized by the FAD-linked oxidoreductase pytB and the
CC       cytochrome P450 monooxygenase pytD to form the fused gamma-pyrone core,
CC       resulting in pyranterreones 7 and 11, respectively (PubMed:32077283).
CC       The hydroxy group at C-8 of pyranterreones 7 and 11 are dehydrated by
CC       the aspartyl protease pytH to form a delta-7 double bond to give
CC       pyranterreones 3 and 1, 2 accordingly (PubMed:32077283). The exo-
CC       methylene of pyranterreone 3 could be reduced into a pendant methyl by
CC       reductase pytE to provide pyranterreone 4, also known as cordylactam
CC       (Probable). Pyranterreone 4 can be reconverted to pyranterreone 3
CC       through pytB-catalyzed dehydrogenation or further oxidized to
CC       pyranterreones 9 and 10 (Probable). {ECO:0000269|PubMed:32077283,
CC       ECO:0000305|PubMed:32077283}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32077283}.
CC   -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC       transcription factor pytR. {ECO:0000269|PubMed:32077283}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of pyranterreone 4, but
CC       accumulates pyranterreone 3. {ECO:0000269|PubMed:32077283}.
CC   -!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
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DR   EMBL; BKZM02000003; GES59608.1; -; Genomic_DNA.
DR   EMBL; MN699961; QIH14019.1; -; Genomic_DNA.
DR   AlphaFoldDB; P9WEZ2; -.
DR   VEuPathDB; FungiDB:ATEG_00912; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR   InterPro; IPR016040; NAD(P)-bd_dom.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF13460; NAD_binding_10; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   2: Evidence at transcript level;
KW   Oxidoreductase.
FT   CHAIN           1..263
FT                   /note="Reductase pytE"
FT                   /id="PRO_0000450470"
SQ   SEQUENCE   263 AA;  28441 MW;  22277527169CB314 CRC64;
     MSSSKPTIAF FGATGGSTIS CLAPALKAGY RCAALARTPS RLRDLLVQRG VSESTIADNL
     TIVSGTATDL QPVKQTLQMG RPASDMADLI VSGIGGKLIM SNPLSPTLDN PTICQDVVRN
     ILTAIRELRD TGTTKAPFLI TLSTTGISEV KRDLPIAMMP MYHWMLKVPH DDKKVMERLI
     VDDAERDPAA RALGGYVIVR PSLLTDGDRD KGGDLKKIRV GVEEAPAVGY TISREDVGRW
     VFEHLVKKGR ESEYAGKAVT ITY