TAZA_ASPTN
ID TAZA_ASPTN Reviewed; 2556 AA.
AC Q0CSA2;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Non-reducing polyketide synthase tazA {ECO:0000303|PubMed:35398258};
DE Short=NR-PKS tazA {ECO:0000303|PubMed:35398258};
DE EC=2.3.1.- {ECO:0000269|PubMed:23621425};
DE AltName: Full=Azaphilone biosynthesis cluster protein A {ECO:0000303|PubMed:35398258};
GN Name=tazA {ECO:0000303|PubMed:35398258}; ORFNames=ATEG_03432;
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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23621425; DOI=10.1021/ja401945a;
RA Chiang Y.M., Oakley C.E., Ahuja M., Entwistle R., Schultz A., Chang S.L.,
RA Sung C.T., Wang C.C., Oakley B.R.;
RT "An efficient system for heterologous expression of secondary metabolite
RT genes in Aspergillus nidulans.";
RL J. Am. Chem. Soc. 135:7720-7731(2013).
RN [3]
RP FUNCTION, DOMAIN, INDUCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=35398258; DOI=10.1016/j.fgb.2022.103694;
RA Sun W.W., Li C.Y., Chiang Y.M., Lin T.S., Warren S., Chang F.R.,
RA Wang C.C.C.;
RT "Characterization of a silent azaphilone biosynthesis gene cluster in
RT Aspergillus terreus NIH 2624.";
RL Fungal Genet. Biol. 160:103694-103694(2022).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of azaterrilone A and other azaphilones,
CC a class of fungal metabolites characterized by a highly oxygenated
CC pyrano-quinone bicyclic core and exhibiting a broad range of
CC bioactivities (PubMed:35398258). The first step of the pathway begins
CC with tazA that assembles one acetyl-CoA starter unit, five malonyl-CoA
CC units, and catalyzes a series of Claisen condensations, methylation,
CC PT-mediated cyclization, and finally releases the first hexaketide
CC precursor through the R-domain (PubMed:23621425, PubMed:35398258). The
CC tazA product then undergoes reduction on its terminal ketone and the
CC following pyran-ring formation by yet undetermined enzyme(s).
CC Dehydration and enoyl reduction, possibly involving the trans-enoyl
CC reductase tazE leads to the next intermediate. TazD is predicted as an
CC acetyltransferase and might catalyze the acetylation steps leading to
CC the synthesis of azaterrilone A. Azaterrilone A is not the final
CC product of the taz pathway and both the highly reducing polyketide
CC synthase tazB and the dual enzyme tazHJ catalyze late steps of the
CC pathway, leading to the production of the 2 final stereoisomers that
CC contain additional polyketide modification whose structures have still
CC to be determined (Probable). {ECO:0000269|PubMed:23621425,
CC ECO:0000269|PubMed:35398258, ECO:0000305|PubMed:35398258}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00258};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:35398258}.
CC -!- INDUCTION: Expression is positively regulated by the azaterrilone A
CC cluster-specific transcription factor tazR.
CC {ECO:0000269|PubMed:35398258}.
CC -!- DOMAIN: Multidomain protein; including an N-terminal starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a
CC acyl carrier protein (ACP) domain, a methyltransferase domain and a
CC reductive NADPH-binding domain that is required for NADPH-dependent
CC product release. {ECO:0000305|PubMed:35398258}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of azaphilone compounds.
CC {ECO:0000269|PubMed:35398258}.
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DR EMBL; CH476597; EAU36706.1; -; Genomic_DNA.
DR RefSeq; XP_001212610.1; XM_001212610.1.
DR STRING; 33178.CADATEAP00010355; -.
DR EnsemblFungi; EAU36706; EAU36706; ATEG_03432.
DR GeneID; 4318027; -.
DR VEuPathDB; FungiDB:ATEG_03432; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_2_1; -.
DR OMA; MGMEMAR; -.
DR OrthoDB; 13314at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
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; -; 2.
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; 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; 2.
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 SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2556
FT /note="Non-reducing polyketide synthase tazA"
FT /id="PRO_0000456064"
FT DOMAIN 1620..1694
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:35398258"
FT REGION 16..270
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT REGION 400..772
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT REGION 876..1209
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT REGION 1257..1564
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT REGION 1830..2107
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT REGION 2180..2424
FT /note="NADPH-binding (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:35398258"
FT ACT_SITE 143
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 270
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT MOD_RES 1654
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2556 AA; 280182 MW; DDE553648E84A02D CRC64;
MAVANHEEAE ATTVLLFGPQ ALSFTEESFQ RIRVALNDTE NAWMRQVVEE LPECTSRVAK
QFPKLQATPA AKLQNSLRDW LRIDEGVAPA ASKSLPNALL TPLVVLDHLA QYSQYVQLAH
VETGLGTDRY GPQSRPTRNL GFCTGLLSAL AVSSASNKAE FRKYAAVAVR LAAVIGALVD
AEDAIGHHGE SKTFSAAYHS SKQESELQSI LQDFPEDADS TGNLQAYISV NYDEGRATIT
TSNRTAQAFQ QRLREAGITA QAIGLRGRFH YQGYQQDLAR LVEICDATPE LRLPDVTDAV
IPIHSLSGGG LITEGRLHHI ALREILVEQS QWGKTFDAMS RSSLANTQSL LVSFGFEKCV
PPSAMPRVGG QVVYMTDQRD ARLRLSAVKT PGEMVSEDEI AVIGMAIKVA GADDADEFWD
LNLTAESQHR EVPAERFTFE THWRTVDPAR KWYGNFVRDH DAFDHKFFQK SPREATTQDP
QQRIFLQSAY QAVEQSGYFN SLHADRNVGV SVITLDGMGM DTSLYPTLYQ VDSGECTAAL
AGGTNIMTSP LWFQNLAGAS FLSQTGPCKP FDAKADGYCR GEGVACVFLK KMTKAIEDGN
TIIGSIRSTA VYQNDNCTPI FVPNAPSLSG LFDDVVRKSG LSPKDITLVE AHGTGTPVGD
PAEWDSIRKT LGGRSVRSVP MPVGSVKGLI GHTECTSGVV ALIKVLLLIH YGIIPPQASF
QTLSPALKAT ADDMLEVCTK QTPWNVEYRA ALINNYGASG SNASMIVTQP PKLRGNGPFS
PPTDGGKYAF WLTGLDERSL RDYARRLSGF LASKKISSLS SLSFNAYRQS NRALPHGLIF
SSSSMEELQT QLTDFAKGNG KLSATTRKPV RPVILCFGGQ ISRFVGLDKA VYESIGTLRT
HLDRCDATLQ SLGLDGLYPG IFERSQVDDP VKLQTMLFAL QYSCAKCWLD CGLQPVAVVG
HSFGELTALC IAGVLTLRDS LQVVAMRAQL IKSSWGPDPG AMMAVEGNLA DVQTLLKNAE
RACPEETPAT VACFNGPTTF TLAGSTKAID AVSECISSVS VVRGKKLSVS NAFHSTLVEP
LKDQLGQLAE GMIFGEAKIR WERATENQTS ANIGPEFFAS HMRDPVYANH ALQRLHREFP
SAIWLEAGSN STITRMANKA LGFPAESYFA DINITSDSAS NTLTESFVNL WKEGLAIPHW
AHHCTQAPAY STLLLPPYQF EKSRHWLELK KPQAVQLIEL PSKAQQEELP TKLYTFVGYQ
DEGKRQARFR VNTMIKAYEE FVSGHLIVQT AAICPATLEV DITIEALFTL CPDFKATGLQ
PQVANVENLV PICVDPSRVL WLDLRATTSD FKSWEWQMVS TNEKGESKST HVKGQIIFQS
AAEAQAEFSR YERLVPHRRC TEILNDSDPD DVLQGRNMYK VFAEIVDYSE PYRGLRKLVG
KGTTSAGRVV KQRSGETWLD THISDCFSQV GGFWVNCMTD RSASDMYIAA GFESWIRRPG
STAAQDDPEK TSVWDVMACH VKASEKAYTT DIFIFDATSG LLSEIILGIN YSRLPKSTMS
KMLTKLTAPS ERRAQVDSPS MPASINAPPS ASEQAPVEPA PQTKESAPIA EPGAGGQSNS
KVPGIVVEVL AELSGVEPDA IKMSTKLADI GIDSLVGMEM VHDLESKCEC SLDMDEMAEV
VTVNDVVQCV HKTLGIEGGS AAQESEGNLT PASSGTQSPR SDPVSDTSLS DLEQLPRKES
DLELQLSASD VLGAFGETKK LTDQFITDFN CAGYMDNINP KQTQLCIALT IEAFEKLGCN
LRTAKAGEAL PRISHAPQHG RLTQYLYDML EHEGRLIDID GDRIVRTAVS VPHKSSKEIL
ASLEAAYPEH VCANRLAFFC GTRLVEVLEG KLDGVKLIFG NEEGRQLVAG LYGDTQLNRI
FYKQMEDILT RLISRIPRDS GPLRILEMGA GTGGTTKYLV PLLAKLGAPV EYTFTDLAPS
FVAAARRQYK AYPFMKFHAH DIEQEPAQDL LGTQHIIIAS NAVHATHSLT VSAKNMRKAL
RPDGFLMMLE MTQTVPWVDI IFGLLEGWWL FDDGRQHAIS PESRWEKDLQ SVGYGHIDWT
DGHLAENKLQ RIIIAMASGP QGGRLPLPAP PIAQSTSNIT ERATAVEGYV DRFTSGFAMQ
PLASAPGTTV RKDSAQCVLV TGATGSLGAH LVKELLGRSD VATVICLNRL SRGTNPEQRQ
YRSFEEKGLK LDSSQSAKLR IIETDTSKPL LGLSAEQYEE VAHMVTAIVH NAWPMSGARP
LRGFEAQFSV MRNLIDLARD AAYVSQTITF QFISSIAVVG HYPLWSRERN VPEERVGIES
ILPNGYGDAK YVCERMLDAT LHKYPDHFRA MGVRLGQVAG SSETGYWNSL EHLSFLVKSS
QTLRALPDFQ GELSWTPVDV VASTLADLVS YAAADFSAAS TVYPIYHIDN PVRQPWKEMI
SVLARALDIP PANVLPFPEW VRRVRRFPGS TEKDNPAFKL IDFLDDNFVR MSCGGLLLDT
RHTQQHSPTL AAQGPVSNQV AEGYIRYWKR TGFLAG
