PYTG_ASPTN
ID PYTG_ASPTN Reviewed; 333 AA.
AC Q0CZG6;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=FAD-dependent monooxygenase pytG {ECO:0000303|PubMed:32077283};
DE EC=1.-.-.- {ECO:0000305|PubMed:32077283};
DE AltName: Full=Pyranterreones biosynthesis cluster protein G {ECO:0000303|PubMed:32077283};
GN Name=pytG {ECO:0000303|PubMed:32077283}; ORFNames=ATEG_00918;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of pyranterreones, a family of antioxidative
CC compounds (PubMed:32077283). The first step of pyranonigrins
CC biosynthesis is performed by the hybrid PKS-NRPS synthetase pytA that
CC condenses 4 malonyl-CoA units ato the acetyl starter unit by the
CC modular PKS of pytA (PubMed:32077283). The acyl chain is then connected
CC to an L-serine through the amide bond by the modular NRPS of pytA
CC (PubMed:32077283). A tetramic acid is formed and released from the PKS-
CC NRPS pytA to give pyranterreone 5 with the help of the thioesterase
CC pytI (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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:32077283}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
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 most pyranterreones,
CC but accumulates high amounts of pyranterreone 5.
CC {ECO:0000269|PubMed:32077283}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; CH476594; EAU39564.1; -; Genomic_DNA.
DR RefSeq; XP_001211004.1; XM_001211004.1.
DR AlphaFoldDB; Q0CZG6; -.
DR SMR; Q0CZG6; -.
DR STRING; 341663.Q0CZG6; -.
DR EnsemblFungi; EAU39564; EAU39564; ATEG_00918.
DR GeneID; 4355681; -.
DR VEuPathDB; FungiDB:ATEG_00918; -.
DR eggNOG; KOG2614; Eukaryota.
DR HOGENOM; CLU_1004639_0_0_1; -.
DR OMA; TWIENAT; -.
DR OrthoDB; 462247at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..333
FT /note="FAD-dependent monooxygenase pytG"
FT /id="PRO_0000450472"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 38..39
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 234..236
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 294..298
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 333 AA; 36581 MW; 5B6521774032A4AB CRC64;
MSATTLPNVS VAIIGAGIGG LTLGAFLRRL GIPFVILERT AVLTPLGAGI SLAPNCLAAL
EQLGLYETIR QNAQELRGIN VYREKRCWGT IDFGLAKQWF GYNVLSIERY EFHRYLYEAA
GGAGVVQLGW DVARIEGLEN ADGDLRVISA DGREVHTDIV VGADGIRSVT RRILSRSMGL
QPENTIRFTG RVHMSGYTKP LSHLSTTDLG IGHWMLYNDC ILTTWPCKEN RQWFIGVKAA
PPDEKSPDRS VWKGATSDTV NAVYGSRFHP FGEDGTVEAS MYAIPAPAIA GNSRDDKLSI
IPNASSLATS SRKPTSRTWF GAEWRSWVMV YRT
