PYTB_ASPTN
ID PYTB_ASPTN Reviewed; 807 AA.
AC Q0CZH0;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 25-MAY-2022, entry version 67.
DE RecName: Full=FAD-linked oxidoreductase pytB {ECO:0000303|PubMed:32077283};
DE EC=1.1.1.- {ECO:0000305|PubMed:32077283};
DE AltName: Full=Pyranterreones biosynthesis cluster protein B {ECO:0000303|PubMed:32077283};
DE Flags: Precursor;
GN Name=pytB {ECO:0000303|PubMed:32077283}; ORFNames=ATEG_00914;
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-linked oxidoreductase; 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; Evidence={ECO:0000305};
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 most pyranterreones,
CC but accumulates pyranterreones 9 and 10. {ECO:0000269|PubMed:32077283}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; CH476594; EAU39560.1; -; Genomic_DNA.
DR RefSeq; XP_001211000.1; XM_001211000.1.
DR AlphaFoldDB; Q0CZH0; -.
DR SMR; Q0CZH0; -.
DR EnsemblFungi; EAU39560; EAU39560; ATEG_00914.
DR GeneID; 4355677; -.
DR VEuPathDB; FungiDB:ATEG_00914; -.
DR eggNOG; KOG1515; Eukaryota.
DR HOGENOM; CLU_349150_0_0_1; -.
DR OrthoDB; 1049549at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 2.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF07859; Abhydrolase_3; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..807
FT /note="FAD-linked oxidoreductase pytB"
FT /id="PRO_5004170676"
FT DOMAIN 60..231
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 351
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 419
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 807 AA; 87872 MW; 7176D7B4DD6FB817 CRC64;
MRFLGIAAVA TFSTVVSAYP KSTALYNCVS SVFGPSAPQR IVTPNDTTYL DSRLGETIQF
DELPVLLAYA QESKEIAPLI RCAKTAGIKA VPRAGGHSFE AYSALNGTLI IDIAHLNYVN
VSDDRQTAVV GAGIRLGALY TALSEHGTSF IGGICPTVGL AGFLGSGGFN MQQRSQGLAV
EHVLAAKVVL ADGRTVVASP DTNPDLFFAI RGGGGGTYGI VVEFTLSLTS IPRSAMLMLS
WNDTASRFPA AKQYLDWAPK QIPEFMSQIN VYRDKVQVLG WYYGGTEDEL RSLVNASGLL
DIGKPAVVIA GGCNTDNARA FGYTTMECLP DGKVDVSILN VVPDPFSKVG NSTQFKWNEV
PKSTSMPVAD PWQRFHRMSK SFFVLKDNPL TDQTLQSLLD RIASLDAKSQ VWGEWHAWNI
STPSKGSGNA FAWREKAYAH LEFQIHGAPD DKERQSTYEN WLEDLESYLR PTVGGASYSG
YLDADISTDP LTSYYGGNVC KLVSVKRKTE NDYSSSTVEQ LFIDSDVNAR KITSRYPIPP
PDKSIKTEDI TLQDCWVRIY TPPSATSSGS VAVFIHGGGW IMGSPDIEDA TCRRICRCSG
MTVVSVGYRL APKFQFPTGL NDCVRATLWT LGHFPVSALV IMGGSAGANL AFGVALKLVD
AGLGEKVKGV LALVPATVHP DAVPADKRDQ YTAMHENANN TVNTLAAMDC FLDAYAAPPH
DKYFSVLLHP RLKDLKKVYL VECGTDTLRD DARLMRDALE EAGVPLMYDA YPGYPHYFWS
YPSPVLAEAS ESFHENMLQA LAWLDQE
