AT325_ASPTN
ID AT325_ASPTN Reviewed; 3890 AA.
AC Q0D159;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Hybrid PKS-NRPS synthetase ATEG_00325 {ECO:0000303|PubMed:21236704};
DE EC=2.3.1.- {ECO:0000305|PubMed:21236704};
DE EC=6.3.2.- {ECO:0000305|PubMed:21236704};
DE AltName: Full=Isoflavipucine biosynthesis cluster protein ATEG_00325 {ECO:0000303|PubMed:21236704};
GN ORFNames=ATEG_00325;
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 IDENTIFICATION, FUNCTION, INDUCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=21236704; DOI=10.1016/j.chembiol.2010.12.011;
RA Gressler M., Zaehle C., Scherlach K., Hertweck C., Brock M.;
RT "Multifactorial induction of an orphan PKS-NRPS gene cluster in Aspergillus
RT terreus.";
RL Chem. Biol. 18:198-209(2011).
CC -!- FUNCTION: PKS-NRPS hybrid synthetase; part of the gene cluster that
CC mediates the biosynthesis of isoflavipucine (PubMed:21236704). The PKS
CC part of the PKS-NRPS ATEG_00325 probably assembles a triketide from an
CC acetyl starter and two malonyl-CoA extender units (PubMed:21236704).
CC The poly-beta-keto intermediate would then be fused to the leucine unit
CC by the NRPS part (PubMed:21236704). The resulting amide would be
CC liberated from the PKS-NRPS through reductive release of the linear
CC PKS-NRPS product from the enzyme complex (PubMed:21236704). Further
CC steps in isoflapucine synthesis include a cyclization step, an
CC oxidation step, a hydrolysis step involving a trans-amidation, and an
CC additional oxidation step, leading to flavipucine (PubMed:21236704).
CC Formation of isoflavipucine from flavipucine requires an unusual
CC rearrangement (PubMed:21236704). Alternative rearrangement reactions
CC could build up rubrobramide, representing a branching of flavipucine
CC biosynthesis (PubMed:21236704). The enzymes involved in the post-PKS-
CC NRPS steps have not been identified yet, but the putative oxygenases
CC ATEG_003329 and ATEG_00330 encoded by the cluster could play a role
CC (PubMed:21236704). {ECO:0000269|PubMed:21236704}.
CC -!- INDUCTION: Expression is inhibited by various sugars, including
CC glucose, fructose, mannose, and ribose (PubMed:21236704). Expression is
CC repressed by the carbon catabolite repressor creA (PubMed:21236704).
CC Expression is increased at alkaline pH in a pacC dependent manner, but
CC glucose repression dominates the effect of alkalization
CC (PubMed:21236704). Nitrogen sources such as amino acids Asn or Gln can
CC also activate expression (PubMed:21236704). Finally, expression is
CC positively controled by the cluster-specific regulator ATEG_00326
CC (PubMed:21236704). {ECO:0000269|PubMed:21236704}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module (PubMed:21236704). 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 (PubMed:21236704). Thus, an NRP
CC synthetase is generally composed of one or more modules and can
CC terminate in a thioesterase domain (TE) or reductase domain (R) that
CC releases the newly synthesized peptide from the enzyme
CC (PubMed:21236704). ATEG_00325 contains also a ketoacyl synthase domain
CC (KS), an acyl transferase domain (AT), a dehydratase domain (DH), a
CC methyltransferase (MT) domain, a ketoreductase domains (KR), and an
CC acyl carrier (ACP) domain (PubMed:21236704). ATEG_00325 has the
CC following architecture: KS-AT-DH-MT-KR-ACP-C-A-T-R/C (PubMed:21236704).
CC The DH, MT and KR domains seem not to contribute to biosynthesis
CC (PubMed:21236704). {ECO:0000269|PubMed:21236704}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of isoflavipucine and
CC dihydroisoflavipucine (PubMed:21236704). {ECO:0000269|PubMed:21236704}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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; CH476594; EAU38971.1; -; Genomic_DNA.
DR RefSeq; XP_001210411.1; XM_001210411.1.
DR SMR; Q0D159; -.
DR STRING; 33178.CADATEAP00006020; -.
DR EnsemblFungi; EAU38971; EAU38971; ATEG_00325.
DR GeneID; 4355077; -.
DR VEuPathDB; FungiDB:ATEG_00325; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_5_1; -.
DR OMA; GYPPISE; -.
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:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
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; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
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; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 2: Evidence at transcript level;
KW Isomerase; Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Repeat; Transferase.
FT CHAIN 1..3890
FT /note="Hybrid PKS-NRPS synthetase ATEG_00325"
FT /id="PRO_0000438997"
FT DOMAIN 2299..2377
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3457..3536
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 7..441
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 552..857
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 942..1105
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1341..1535
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2058..2201
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2271..2292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2427..2449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2474..2904
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 2938..3337
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255"
FT REGION 3574..3803
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2274..2292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2337
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3496
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3890 AA; 422881 MW; 0453C45205A2B9BB CRC64;
MSSNEPIAII GSSCRFAGGA SSPSKLWDLL LKPKDLSKPP PESRFNLEGF YHPNAEQHGN
TNIHGSYFLE EDPRCFDTVF FNISPKEAEA IDPQQRILLE VVYEAMEAAG LTLQGLQGSD
TSVYAGLMIR DYMDVQVRDP DFFSQYMVTG TSSALNANRI SYFFDWHGPS LTVDTACSSS
LVAVHQAVQG LRAGESRVAC VTGSNLLLGP ELFISASNMH MLSSRSKMWD VSAEGYARGD
GFASFMLKTL SNAIADGDHI EAIIRETGVN SDGRTKGITL PSPQAQADLI RDTYRRAGLD
LSNPNDRCQY FEAHGTGTQA GDPREASAIH DAFFGAEGDD NKTGPKLVVG SIKTIVGHTE
GTAGMAGMLK ALLAIRHRVI PPNLHFNNLN PSVAPFYDRL TVPTESIPWP VVAPGTPLRA
SVNSFGFGGT NAHAIVESYE PDNRSSITGQ NDGIVLPLVL SAHSDKALAS VVENYAAFLR
QTQQTLCLRD LAWTLHSRRS NLPVKAAFSG LSASDIAQQM QDRLESVRNT PGTELGIRSP
AIASKKPSLL GVFTGQGAQW PTMGKHLIEN SRTFRETIER LEKSLSELDD GPDWSLKGEI
LAQKAQSRVA EAALSQPLCT AIAIALVDLL HASGVSFTAV VGHSSGEIGA AYAAGVVTAE
EAMKIAYYRG KYAKLAKGEH GAKGGMLAVG MGFNEAKEFC DQPAFKSRLG VAASNSPTSV
TLSGDLDVVR EAKELLDARK TFARMLQVDT AYHSHHMLPC ADPYVSSLNA SRIQPNEPAK
SSCSWISSVY GSEGDPTAEE LSATYWRDNM AQAVLFSQAL ERAMIECGPF DAVLEVGPHP
ALKGPASQTL RELSDGPLPY FGVLDRKRND VVAFGDALAS LWLHFGPSAV DFEGYAAASG
PEDLPPPKLV KDLPAYPWDH SQIYWRESRL SREFRTRASP PHELLGHPLP AGSSEDGLRW
RNILRIEEVP WIGDHRFQGQ ALLPTSAFCS MAVDAALKLA AGSVDPVADG IELHDLVIHN
AVSIPDGSQG VEIITSIQRL EVTNHPLDAE VTVLFGPPDG SKVLKKAASA RVILLHANSV
DEPATLQARE KNLSSIDVPQ FYQSIALVEG CIQTAYAAFS APGDASLRPV FLPQKIERMS
LRLPSVSSSD SWLIIDSFVT GVEKATPNTS PAFHADIEVA DSVSGKLLVE IEGVTISSFS
PTSAADDREL FLQTVWKPVV SEGLSVGNEQ RKVANQAALD MEHQSILYLE NLLANNLYLS
GHLSQEFEWL LQLNLPSHSK GRQHNDGAED VSHLDDFETL RAVAKNLPEL IRGRLPGADI
ERQLQAFVET NSVFTRIKVG LHTLIDQIAH RFAHLNVLEI APAHLSPSFD AFNDLVESIS
SYTLVTNSPS KDVAKYGKKL KHIGVEALHS DPSAIASALS GQKHDVVIAS YLLNGQTASF
SEEALRQFRK VLKAGGYLVL VEPTQEYVWS RIFLGVLLGS ASNSDHGRDI GHHVSSVSLD
GLLRKVGFSG IDSLLPRDAN GPGDAISLFV TQALDETIDL LRHPLQPSAL GILDGRRVLV
VGGKTLQTSR LWHNIASILR PWTKEVHCIE SFEALEEKDS TGIAGAIVLT DLDEPASKLL
TTKSYQAISG LFAQAPHVLW VTQGALEANP EQAASIGLGH FLAQEHSSVH SQFLNLDTVE
ESEYKILGSF MRLLIPGIHD PQESRLWTTE TEISVKNGRV FIPRVFPARG LNDRLNSHWR
PIIQSANTLN DTTSLSASGS LHAATFTAQH FSSSSSAERR PILRTTQSIP IAINVSNGIY
LYLSAGQVDD VGDVLAFTDT MSSRAPALAT WKVPPAESGP VELSNILELT ANVLVAQHIF
DSLPAGNSVL LEPSYTLATI INELTKGADK KVHFLTTAAR EETGSVTWTT IPPLASKRHI
LSALPPCPKL FFDLSPKPNR LSSRIVSLLP VDCALVGPGE LFQLSSEGAE EVSTPWLQHV
LLTVASSAVK LSRKATYPSS STLILSDLLE HGIRNANAVT VVDWTQQTSV PVTVEPLEPS
QFLSPAGTYV LIDIEQPLIQ SIADWLIANG VRSLVAINSD IGERNGRELL DELKVKRLKV
DLANLHDVKD VFDGLTKVTG VIYGGASAAM ANFGEDDAPL QTLQNVEQSA HNLTTILENQ
EVGFFIILSS LQKDRAPVNA YFTSLAAHWK QRRLPTAVLS LESQVHSDPE GPFTHLSESD
VHYALTEAIS SAQSQNDVSA IWTGVKRLPR DIPASSQWSW LSKPLFAHYT QREQEAEPGS
SQGEAQSMVQ RLAASKSHEE ASLVIQEFFL TRLAVMLTLS QESLSSSNDL TSLGVDSLSA
SDIRAWFLKE LDVDVSILKI LGGSTIADLC NEVAAGLTLQ IGSQEEAESQ PAVNSPEPVT
AAPVPEQPTV ERHVESQEPV VEAAVVASSS DSSSEGTMTP PSSRGINTPH TEITNLQLES
VKSKACTAVQ RREKMSFSQN RLWFPSAYLE QETPFNCTTS YTLTGPLDTA RLENAFQRLI
QRHESFRTAF YTDEVSGAAM QRVLASSPFQ LRTMLGNKDD MQRVFRQIAN YHFDLSVADT
LVATLISHGP KDHTIVFGYH HIIMDGVSWQ ITLNDLARFY ESDNPELPQL SQYIEFSVKQ
RQLVSSGAHD AKLSYWRKEF PSAPPLLPLF PFAKVGARKA LTRYDTLDYI YDVDVSLVSK
IKKASLAAKT TTFHFYLAAF VVLLNRFLEI DDVCLGIIDA NRSDKTFLNT VGFLLDMLPL
RLKVNKKERF VHTLRNTRAK AYNALEHSGV PLETILKELQ VPTSATNTPL FQVLMNYRMG
ALRAPQMGDA KMNFLDYEDA KAPFDLAISI DEKDDGTGML TFSMQDYMYD WEGAELLVKT
YVHLLDTLAT DSSQRINEVS LFDESLVNQS MVAGTGPVTG LDWAGTETIS QRVDAMTAQR
PDGVAVKDLN GKARTYAETQ ARVYALASSL QQAGITSGAR VAVYCEPTVD TVALVLAIYR
VGAAYIPLDV RNSHERLADV VRECKPTLIL YHGATKHTLV DVAGDGQDAL DIDTVPQSAA
PIPDVSKLSD PAVILYTSGS TGKPKGIMLT HANLSLQFAS ISSALDLTDR DVVLQQSALG
FDASLSQMFM ALTNGGTLIH GSNRGDPVDL AALIEREGVT LTLIMISEMS ALLQYGSDIL
SRCQSWRIAL CGGEAFTVNL LRKFRDLNLP NLELYNAYGP TEASIMSSLG KVAYRRTDWG
DGSVVPVGPP LPNYGVYVLD ENFQPCPLGW PGELCICGPG VAEGYVGLPE LTSSKFQPDQ
LRKPQGPSYD GWVRVYRTGD KARLLQDGSF VFLGRMDGDS QVKLRGIRIE LNDISNSIVK
TSKEAIVDAA TIVKGTTSQT LVSFVVFAPA KVVDLERSNS SASAYLRQVI QSLPLPVYMR
PAIAVPLERL PFTERGKLDT KALAAIPIQE DEETVNEELS ETEQKLKQVW QDILSEQGMS
LEIRRQSDFF SVGGNSLMLM RVRAKMLEVF GVSVPLAELF QASTLETLAS RLDGNKTAES
DNIVWNEETA LDVSLPPAIA HPRDHPEKDL SVILTGSTGF LGRAIVRQLI ADPRISTIHC
LAVRPGRTLP EELVGSSKVI VYTGDLAAKR LGLSAPQAQE IFSSAAAIIH NGAEVSHMKS
YHSLRPTNVD STRQLVELAL RSSIDSAVRT PAFHYVSTAG VGHLLGIPAF PEQSVSSSPP
PVDGSDGYVA AKWASERILE QASERLGLPV FIHRPSNITG PDVGDRDIIH NVWRWSEVLR
AVPDLVAAGA KGAFDFVGVE TCAKGITDTL FVQASAGHLA YIHQSGENVI PVEEFGECLQ
RNGGADVELV PFDQWVDKAV QAGLDDLVAS FLRGTKGAFQ MPFLPKGLRQ
