ADAA_ASPNC
ID ADAA_ASPNC Reviewed; 1793 AA.
AC A2QX22;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Non-reducing polyketide synthase adaA {ECO:0000303|PubMed:21866960};
DE Short=NRPKS adaA {ECO:0000303|PubMed:21866960};
DE EC=2.3.1.- {ECO:0000269|PubMed:21866960};
DE AltName: Full=2-acetyl-2-decarboxamidoanthrotainin biosynthesis cluster protein A {ECO:0000303|PubMed:21866960};
GN Name=adaA {ECO:0000303|PubMed:21866960}; ORFNames=An11g07310;
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, DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21866960; DOI=10.1021/ja206906d;
RA Li Y., Chooi Y.H., Sheng Y., Valentine J.S., Tang Y.;
RT "Comparative characterization of fungal anthracenone and naphthacenedione
RT biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like
RT cyclization catalyzed by a dimanganese thioesterase.";
RL J. Am. Chem. Soc. 133:15773-15785(2011).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the linear tetracyclic TAN-1612
CC neuropeptide Y receptor antagonist (PubMed:21866960). The decaketide
CC backbone of TAN-1612 is synthesized by the non-reducing polyketide
CC synthase adaA via condensation of one acetyl-CoA starter unit with 9
CC malonyl-CoA units. The FAD-dependent monooxygenase adaC then performs
CC hydroxylation at C2 while the polaketide chain is still attached to the
CC NRPKS adaA (PubMed:21866960). The alpha-hydroxylation step at C2
CC appears to be crucial for the following C18-C1 Claisen cyclization and
CC release of the C9-hydroxyl version of TAN-1612 from the NRPKS adaA, two
CC steps performed by the lactamase-like protein adaB (PubMed:21866960).
CC Finally, the O-methyltransferase adaD performs the C9 O-methylation to
CC complete the biosynthesis of TAN-1612 (PubMed:21866960).
CC {ECO:0000269|PubMed:21866960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 9 H(+) + holo-[ACP] + 9 malonyl-CoA = 3-(2,4-
CC dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-tetrahydroanthracene-
CC 2-carboxyl-[ACP] + 9 CO2 + 10 CoA + 2 H2O; Xref=Rhea:RHEA:64088,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16518, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:149687; Evidence={ECO:0000269|PubMed:21866960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64089;
CC Evidence={ECO:0000269|PubMed:21866960};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:A0A0K0MCJ4};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:21866960}.
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; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000305|PubMed:21866960}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM270243; CAK40778.1; -; Genomic_DNA.
DR RefSeq; XP_001394705.1; XM_001394668.1.
DR AlphaFoldDB; A2QX22; -.
DR SMR; A2QX22; -.
DR PaxDb; A2QX22; -.
DR EnsemblFungi; CAK40778; CAK40778; An11g07310.
DR GeneID; 4984951; -.
DR KEGG; ang:ANI_1_2242094; -.
DR VEuPathDB; FungiDB:An11g07310; -.
DR HOGENOM; CLU_000022_6_1_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
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 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; 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; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
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 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; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1793
FT /note="Non-reducing polyketide synthase adaA"
FT /id="PRO_0000446354"
FT DOMAIN 1716..1793
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:21866960"
FT REGION 16..250
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 391..824
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 923..1245
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 1312..1634
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:21866960"
FT REGION 1642..1714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1659..1712
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 561
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1753
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1793 AA; 195059 MW; 28CB0F259DB58DE0 CRC64;
MSGPTKLVFF GNEFPNDDLK ALFRGLHRHG KDRRFRQLAT FLEESTRVLQ NEVAQLPEPL
KKLVPHFENL MPLTEVDFRQ GPLGAAMESA LLTILELGMF IGHYEAEERV WDLSADRTTL
AGLSIGLLAA AGVALSTHLA EVVQNGAECV RVSFRLGVYV HDISRKLEAP QADGSLLSWA
HVVTGETASD LQEELSRYNT ETGTPELLKV FISAADKTSV SVSGPPSRIR AAFRASQRLR
YSKSLALPVY DGLCHAAHLY DEETIHRVLH PDGSVIPTSR PVQLALLSSR SGQPFEATTA
AELFRAISTE LLTGTIFLDN ITAGILDRTE RCADAPQCQI ETYRTSLVFK GLLKALEACF
PDRTISTTDL IPWVFQDYGA RQPKSYADSK LAIVGMACRM PGGANDLDLF WELLAQGRDT
HTTVPADRFD LETHYDPTGE TENATRTPFG NFIDQPGLFD AGFFNMSPRE AEQTDPMHRL
ALVTAYEALE MAGIVSGRTP SSNPKRIATF YGQASDDWRE LNASQNIGTY AVPGGERAFA
NGRINYFFKF GGPSFNLDTA CSSGLAAVQA ACSALWAGEA DTVLAGGLNI ITDPDNYAGL
GNGHFLSRTG QCKVWDQSAD GYCRADGVGS VVIKRLEDAE ADNDNILAVV LSAATNHSAE
AISITHPHAG AQKENYTQVL HQAAVNPLDI SYVELHGTGT QAGDAQEAES VLDIFAPRAH
RRRADQPLHL GAVKSNIGHG EAAAGIASLL KVLLMYQKNE IPAHIGIPTV INPAIPTDLE
QRQVYLPRTK TAWPRAAGQI RRAIVNSFGA HGGNTTLVLE DAPEKQVTVA REERSTHPVV
ISAKSKKSLA ANVETLLAYL DENPETDLGD LSYTTCARRM HHSWRLATAV SDIPALQKFL
RNAVSNDAVS QTRPIPTEAP HVVFTFTGQG AYYAGLAQGL FQALPFFRAE VRQLDHLSQR
LGFPSIVPVI LGEVEEGTAT ALVTQLSIVI VEIALARLWL LLLGIPAPHA VIGHSLGEYA
ALAVAGVLST ADALYLVGHR AQLIEEHCTP GSHAMLSVRA TIADIERLVG TGADAPTYEL
SCQNTHQDTV IGGSIQDLNA IREKLEPEGI KCVNVDVPFA FHTAQMDAVR ERLAKAVAAV
PFKTPSVPVL SPLLGSVVFD GKSINPEYIV RATREPVRFA TAIDAAQELG IVNSQTLWVD
IGPHPICASF VRSLVPGARI VSSCRRNEDN FATMAKSLCT LHLAGRTPSW AEYFRPDEQA
YSLLRLPKYR WNEVNYWIQY LGTWTLDKAH LKNGGSQKRT ITDVPSVSSL RTSLIHQVTE
ETVDKTTATL KAISDIQHPD FLEAVHGHTM NNCGVATSSI WTDMAMTVGE HLYRRLVPGT
DHVLMDLCDF EVQHAQVANT NSNTPQPLAL EAHLDLPTRH MSLAWYDVNA TTNQRADAPF
ATGSIKYPAD PTGAAWSIEW SRITHLIQGR IEALQHLAAE NKASTLSKPL AYALFKNVVD
YAPRYRGMDR VVIHDHEAFS DITLTTDRHG TWHTPPHWID SVSHLAGLVM NGSDASNTRD
FFYVTPGCGS CRMTEPLIAG GKYRNYVRMF PMPDEAHMYA GDLYILREDK IIGVVEQLKF
RRVPRLLMDR FFSPNKNAAA HAAPAPAPAA VPAVKKQPPT ETIQPQAPKT EQKQDQLQLP
NLASAAPSTA NSSSSPSSSG VATPTTEQEA PVADASAVTG VAGKCLELIA NETGLGVAEL
TADATFVQLG VDSLMSLVLS EKLRSEMGLE IKSSLFLECP TVGDLTGWLE QYC
