EPAA_ASPNC
ID EPAA_ASPNC Reviewed; 2617 AA.
AC A2QTE9;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Non-reducing polyketide synthase epaA {ECO:0000303|PubMed:30384904};
DE Short=NR-PKS epaA {ECO:0000303|PubMed:30384904};
DE EC=2.3.1.- {ECO:0000269|PubMed:30384904};
DE AltName: Full=Pestalamide A biosynthesis cluster protein A {ECO:0000303|PubMed:30384904};
GN Name=epaA {ECO:0000303|PubMed:30384904}; ORFNames=An09g01860;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, FUNCTION, DOMAIN, AND PATHWAY.
RX PubMed=30384904; DOI=10.1016/j.micres.2018.10.004;
RA Wang B., Li X., Yu D., Chen X., Tabudravu J., Deng H., Pan L.;
RT "Deletion of the epigenetic regulator GcnE in Aspergillus niger FGSC A1279
RT activates the production of multiple polyketide metabolites.";
RL Microbiol. Res. 217:101-107(2018).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of nigerpyrone and its derivatives
CC carbonarone A and pestalamide A (PubMed:30384904). The biosynthesis
CC pathway begins with the polyketide assembly by epaA to form
CC phenylacetyl triketide precursor from successive condensation of two
CC malonyl-CoA, presumably with one phenylacetyl-CoA starter unit produced
CC by the phenylacetyl-CoA ligase epaB (PubMed:30384904). For the
CC nigerpyrone biosynthesis, the reactive polyketide chain is released as
CC an aldehyde through the R-domain. A nonenzymatic cyclization and
CC dehydration may create nigerpyrone (PubMed:30384904). For the
CC biosynthesis of carbonarone A and pestalamide A, an extra methyl group
CC is added through the C-methyltransferase domain. Several further steps
CC involving the dehydrogenase orf1, the cytochrome P450 monooxygenase
CC orf2 and the FAD-dependent monooxygenase orf3 are required to form a
CC carbonarone A precursor which is converted to carbonarone A via
CC cyclization (PubMed:30384904). The O-acetyltransferase epaC could
CC catalyze the transfer of 2-methylsuccinyl-CoA, a common intermediate in
CC the ethylmalonyl-CoA pathway, to generate the final product pestalamide
CC A (Probable). {ECO:0000269|PubMed:30384904,
CC ECO:0000305|PubMed:30384904}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30384904}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit, a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone, a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA, a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone, an acyl-carrier protein (ACP) that serves
CC as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm, a methyltransferase domain and a reductive
CC NADPH-binding domain that is required for NADPH-dependent product
CC release. {ECO:0000305|PubMed:30384904}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of nigerpyrone,
CC carbonarone A and pestalamide A. {ECO:0000269|PubMed:30384904}.
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DR EMBL; AM270194; CAK40124.1; -; Genomic_DNA.
DR AlphaFoldDB; A2QTE9; -.
DR SMR; A2QTE9; -.
DR PaxDb; A2QTE9; -.
DR EnsemblFungi; CAK40124; CAK40124; An09g01860.
DR VEuPathDB; FungiDB:An09g01860; -.
DR HOGENOM; CLU_000022_6_2_1; -.
DR Proteomes; UP000006706; Chromosome 1L.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR041068; HTH_51.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2617
FT /note="Non-reducing polyketide synthase epaA"
FT /id="PRO_0000446154"
FT DOMAIN 1653..1727
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30384904"
FT REGION 95..231
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT REGION 375..793
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT REGION 902..1193
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT REGION 1310..1589
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT REGION 1600..1651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1728..1799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1970..2158
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT REGION 2240..2485
FT /note="NADPH-binding (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30384904"
FT COMPBIAS 1745..1799
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 132
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 250
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 539
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1687
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2617 AA; 287801 MW; E45F8C02FEDF16AB CRC64;
MVTTTRATNP TNTLLLFGPQ ALSFSTATFA DIHARVVQTS ENAWIKQTIT SLPGLWDALV
KEFPQYGALE GKQLLRDLDR WFETGTMEHA EPHLPNILLS PMVVITQLTE YVDYLKTMPH
AADQQTETVG FCTGLLTALA ASLASDIKGI RQYGAIAIKL AMIIGAVVDV QDITSPNGPS
KSLAVAWDSA ETQDRLNQII DQSPEVYISV EYDYNRATIT TAARSISSLQ QRLRNAGLIA
SEIGLRGRFH CACYKNDIEA LSKFCDSVPS LCLPDAAVLV LPTRSNDAGS FILSGKLHHC
ALRSILLDTS HWYQTLEVIR QSCLKSPSSM VVSFGPERCI PPSILKGLSS IVTTAAEYQP
SYLHRDPELC NPNEIAVIGM SCKVAGADDV DEFWDLLCKA ESQHQEVPKE RFGFESAFRE
VDPTRKWYGN FINEHDCFDH KFFKKSAREI AATDPQQRQM LQVAYQAVEQ SGYFTTPKSD
KDRKIGCYIG VCAADYEYNV ACHPPNAFMA TGNLKSFVAG KISHWFGWTG PGLCIDTACS
SSLVAVHQAC QAILTGDCTA ALAGGANIIT HPLWYQNLAA ASFLSPTGQC KPFDASADGY
CRGEGFAAVF LKKMSAAIAD GDMIIGSIKA TAVNQNQNCT PVFVPNAPTL SDLFRDVLDR
SQLTANQITV VEAHGTGTQV GDPAEYQSIR NVLGGPSRST PLLFGSVKGL VGHTECTSGA
VSLVKTLLMQ QHEAIPPQPS FDRLNPEIPV SESDNMQIAT RFSPWTAEYR AALINNYGAC
GSNASMVVAQ APRTEQRRSA TRRTSVVLDY PFRLCGSDDR ALRAYSERLL RFIASGIKDG
ISVADLAFNV CRQSNPTLDR SLAFACRTTQ EVEEKLRAFV AGNQGLIATS RSKTPREVIL
CFGGQISNYV GLDREVYDNV ALLRKHLAIC DAACRDLGVD SIFPGIFQKS PISDPVKLQT
ILFSTQYSSA KAWMDSGVRP VAAVGHSFGE LTALCATGIL SLADAMKMIV GRATVIRDFW
GEDKGSMIAV EADENRVQRL LAEAAKQCEL IHARAPTIAC VNGPTSYTLA GPVKSIDIVT
EVISKLSDSG PSIRSKRLKV TNAFHSTLVE PLMEELEKVG QHLTFNTPTM QLERAIKHYS
DATLTSDYVY DHMRNPVYFN QAVQRLAQQY PDSVWLEAGS NSTITSMASR ALGSPRSLHF
QAVNITSDDS WSMLITSTLS LWKQGISTNF WAYHAEQTYE YNPVLLPPYQ FEPSRHWMEL
KVPSSMNNGK VQCGARDEEG PPKTLWSLIE ASDKVARFQI NTAAPKYVEL VSGHVIANTA
PICPATVEVD IVVEALRSLR PDFMDSNLQP QVLAVTNQSP ICIDPNRSVW LECQAMDSNS
VWEWRIVSDS LQEPGTSSSA HVLGKLAFLS GQDEVKQQES EFMRLERLIG HQRCVDLLNT
TEADDIIQGR NIYTTFAGVV DYGEQYRGLK KIVGKGLESA GRVQKKPSEE SWLDAHLGDC
FSQVGGIWVN CMTDHNPDDM FIATGFEKWV RSPALRHGQP RSEIWDVLAC HHRSSEQTYL
TDIFIFDAEQ GALTEVILGI NYHKVAKASM SKILSRLSGT EAAPSSSTRA HPTSSSSPRL
PGPSVPEDKS QNETQPAGTN AVAKKKSEKS AQQNVLEKTR ALLAEISGLE PSEIEAETGL
ADIGIDSLMG MELARDLEAL FKCPLLGDEL ANVTTFQGLV EYVQSAVGVP TNGDEPDNTN
ADEVSEEDNL APSPSSSSSS TNLTEDSSLD QAETTTNISS YPGQTKTEKP AMPPASSKTL
ELSPSWVLEA FEESKRLTDH FIEQYRCANY VDTTLPKQTQ LCVALTVEAF EQLGCPIRTA
VAGQKLERII HIPKHAQLAQ YLYRLLSADA RLIDLTEDGR ITRTHMALPK PSDQILQDLL
RLYPDHEWAN RLAAFTGARL AEVLKGETDG LGLIFGTDEG RELVAGLYGD SLLNKLSYRQ
MEDIITRLAS RIPRDSGPLK ILEMGAGTGG TTKGMAPLLA RLGIPVEYTF TDLSGSFVAA
ARKKYQKEYP FMKFQVHDIE KPPSDQLRHS QHIVIASNAI HATHSLTDSS RHVREFLKTD
GFLMIVEMTQ PVHWVDIIFG LFDGWWLFAD GRDHAIASAG WWEKVFQSVG YGQVDWTDGH
RPEVQIQRVI IAFASGPRYG RQPLPPAPPP NLVPGSHASR QAAVNEYLDK YTKGFTLPAQ
TSNPDISNST SYWEKQCVLI TGATGSLGVH LVAAVAALDD VQTVICLNRR SPMDPDLRQQ
QAFERRGILL EAASMSKIRV LQTDSSKPQL GLTDEVYSSL VTSTTHIIHN AWPMTGKRPL
SGLEQQFQVM RNLLDLAAQC SSTRPANVPR IVFQFISSIA TVGYYPLWSG QTLVPETCMG
IESVLANGYG EAKYVCEQML DRTLHQYPDR FRAMAVRLGQ IAGSRTSGYW NPMEHLSFLF
KSAQTLQVFP DFTGDLCWTP VNDVAATLSD LLLLSPHSSS MTDQPIYHID NPVRQSWSEM
VPVLIDALGI PAQNVFPFAD WVCRVRAFPG QVEWDNPAAL LIDFLDDHFL RMSCGGLLLD
TKRACEHSPT LAAVGPVTAE LARKYIQSWK EMGFLNP
