PYTA_ASPTN
ID PYTA_ASPTN Reviewed; 666 AA.
AC Q0CZH1;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Hybrid PKS-NRPS synthetase pytA {ECO:0000303|PubMed:32077283};
DE EC=2.3.1.- {ECO:0000305|PubMed:32077283};
DE EC=6.3.2.- {ECO:0000305|PubMed:32077283};
DE AltName: Full=Pyranterreones biosynthesis cluster protein A {ECO:0000303|PubMed:32077283};
DE Flags: Fragment;
GN Name=pytA {ECO:0000303|PubMed:32077283}; ORFNames=ATEG_00913;
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: Hybrid PKS-NRPS synthetase; 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 -!- 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 -!- DOMAIN: The N-terminal part acts as a polyketide synthase and includes
CC a ketosynthase (KS) domain that catalyzes repeated decarboxylative
CC condensation to elongate the polyketide backbone; a malonyl-CoA:ACP
CC transacylase (MAT) domain that selects and transfers the extender unit
CC malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to
CC enoyl groups; an enoylreductase (ER) domain that reduces enoyl groups
CC to alkyl group; a ketoreductase (KR) domain that catalyzes beta-
CC ketoreduction steps; and an acyl-carrier protein (ACP) that serves as
CC the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000250|UniProtKB:P9WEZ4}.
CC -!- DOMAIN: The C-terminal part acts as an NRP synthetase composed of
CC discrete domains (adenylation (A), thiolation (T) or peptidyl carrier
CC protein (PCP) and condensation (C) domains) which when grouped together
CC are referred to as a single module. Each module is responsible for the
CC recognition (via the A domain) and incorporation of a single amino acid
CC into the growing peptide product. PytA contains one module and
CC terminates in a thioesterase domain (TE) that releases the newly
CC synthesized peptide from the enzyme. {ECO:0000250|UniProtKB:P9WEZ4}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of pyranterreones.
CC {ECO:0000269|PubMed:32077283}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
CC -!- CAUTION: In A.terreus strain NIH2624, ATEG_00913 misses most of its
CC catalytic domains. This difference may be due to errors in the
CC sequencing or the automatic annotation of genome. The protein consists
CC of a highly reducing PKS module (KS-AT-DH-ER-KR-ACP), a single NRPS
CC module (C-A-PCP), and C-terminal TD domain.
CC {ECO:0000305|PubMed:32077283}.
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DR EMBL; CH476594; EAU39559.1; -; Genomic_DNA.
DR RefSeq; XP_001210999.1; XM_001210999.1.
DR AlphaFoldDB; Q0CZH1; -.
DR SMR; Q0CZH1; -.
DR STRING; 341663.Q0CZH1; -.
DR EnsemblFungi; EAU39559; EAU39559; ATEG_00913.
DR GeneID; 4355676; -.
DR VEuPathDB; FungiDB:ATEG_00913; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_16_6_1; -.
DR OMA; MLNDKDF; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
PE 2: Evidence at transcript level;
KW Ligase; Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN <1..>666
FT /note="Hybrid PKS-NRPS synthetase pytA"
FT /id="PRO_0000450466"
FT REGION <1..343
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32077283"
FT REGION 455..665
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32077283"
FT ACT_SITE 87
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 548
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT NON_TER 1
FT NON_TER 666
SQ SEQUENCE 666 AA; 72588 MW; 08C48957B198556A CRC64;
MDPQQRLLLE VVYEALEDAG ITLDEIQGSL TSVYCGCFTN DYNAMTTKDL EYYPKYTVTG
TGNSILANRI SYFYNLHGPS ATVDTACSSS LVCFHLGAQS LRDAEADISI VVGSALHFDP
NIFITMTDLG MLSTDGRCRH GDAAGSGYVR GEGIAAMVLK RQDRAQADGD HIRAVVRGTG
VNHDGRKQGI TLPSARAQAD LITSTYERAG LEPAETTYVE CHGTGTKAGD PRELRAVHEV
FCRHRPDTLH VGSVKTNIGH LEGASGIAGL MKATMALEKK IIPPNMHFST PNPEVDFKNW
KLEIPTEPKV WEMGRRTIPR RASINSFGYG GTNAHAILEE YNSFGSKTTA CQQPTVSLPP
ELAAMVERRP YLLPLTSHSE RAGELWAERL AQYLTENEAS VADVALSLST RRTMHRFRSF
AVSADMEKVI ERIRDPPPGA AWKSKLDTIP RIGFVFTGQG AQWFGMARSL LEQCPLFLQT
IRKCDRILQA LPSHRPTWSV EAELLKSQQD TMLGRTEYSQ PICTAVQLAL VDVLAHWGVK
PSGVVGHSSG ELAATYAAGL LSFENALVAA YYRGVHMGSG AAAPGSMPGA MMAVGMTEAE
VTAELEPYRG RIAIAAMNSP SSFTVSGDED AVVELQQALT DRKVFARRLQ VAQACVFVHS
LVIKRY
