ATPKS_ASPNA
ID ATPKS_ASPNA Reviewed; 1854 AA.
AC G3XNF4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=PKS-NRPS hybrid synthetase ATPKS {ECO:0000303|PubMed:32159958};
DE EC=2.3.1.- {ECO:0000269|PubMed:32159958};
DE AltName: Full=Pyrophen biosynthesis cluster protein ATPKS {ECO:0000303|PubMed:32159958};
GN Name=ATPKS {ECO:0000303|PubMed:32159958}; ORFNames=ASPNIDRAFT_41846;
OS Aspergillus niger (strain ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 /
OS NCTC 3858a / NRRL 328 / USDA 3528.7).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=380704;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 / NCTC 3858a / NRRL
RC 328 / USDA 3528.7;
RX PubMed=21543515; DOI=10.1101/gr.112169.110;
RA Andersen M.R., Salazar M.P., Schaap P.J., van de Vondervoort P.J.I.,
RA Culley D., Thykaer J., Frisvad J.C., Nielsen K.F., Albang R., Albermann K.,
RA Berka R.M., Braus G.H., Braus-Stromeyer S.A., Corrochano L.M., Dai Z.,
RA van Dijck P.W.M., Hofmann G., Lasure L.L., Magnuson J.K., Menke H.,
RA Meijer M., Meijer S.L., Nielsen J.B., Nielsen M.L., van Ooyen A.J.J.,
RA Pel H.J., Poulsen L., Samson R.A., Stam H., Tsang A., van den Brink J.M.,
RA Atkins A., Aerts A., Shapiro H., Pangilinan J., Salamov A., Lou Y.,
RA Lindquist E., Lucas S., Grimwood J., Grigoriev I.V., Kubicek C.P.,
RA Martinez D., van Peij N.N.M.E., Roubos J.A., Nielsen J., Baker S.E.;
RT "Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015
RT versus enzyme-producing CBS 513.88.";
RL Genome Res. 21:885-897(2011).
RN [2]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND PATHWAY.
RX PubMed=32159958; DOI=10.1021/acs.jnatprod.9b00989;
RA Hai Y., Huang A., Tang Y.;
RT "Biosynthesis of Amino Acid Derived alpha-Pyrones by an NRPS-NRPKS Hybrid
RT Megasynthetase in Fungi.";
RL J. Nat. Prod. 83:593-600(2020).
CC -!- FUNCTION: PKS-NRPS hybrid synthetase; part of the gene cluster that
CC mediates the biosynthesis of pyrophen and campyrone B, which represent
CC a class of fungal amino acid-derived alpha-pyrone natural products
CC (PubMed:32159958). The first step of pyrophen biosynthesis is catalyzed
CC by the PKS-NRPS hybrid synthetase ATPKS that uptakes and condensates L-
CC phenylalanine and malonyl-CoA in order to produce
CC desmethyldesacetylpyrophen (PubMed:32159958). Although the A domain
CC does not discriminate between 2 enantiomeric phenylalanines, the
CC downstream KS domain must play a gate keeping role to stereoselectively
CC accept the L-phenylalanyl-S-phosphopantetheine (Ppant)-T domain
CC intermediate for chain elongation (PubMed:32159958). The resulting
CC amino acid derived diketide is off-loaded through lactonization to
CC yield the alpha-pyrone intermediate desmethyldesacetylpyrophen
CC (PubMed:32159958). The cluster-specific O-methyltransferase (OMT) then
CC methylates desmethyldesacetylpyrophen to desacetylpyrophen, which is
CC further acetylated to pyrophen by an endogenous yet unidentified N-
CC acetyltransferase (PubMed:32159958). ATPKS has relaxed substrate
CC specificity to activate and extend branched-chain amino acid L-leucine
CC to produce small amounts of campyrone B (PubMed:32159958).
CC {ECO:0000269|PubMed:32159958}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:32159958}.
CC -!- DOMAIN: The architecture of ATPKS is the following one: adenylation
CC (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase
CC (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain,
CC and thioester reductase (TE) domains. {ECO:0000305|PubMed:32159958}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; ACJE01000002; EHA27898.1; -; Genomic_DNA.
DR AlphaFoldDB; G3XNF4; -.
DR SMR; G3XNF4; -.
DR STRING; 380704.G3XNF4; -.
DR EnsemblFungi; EHA27898; EHA27898; ASPNIDRAFT_41846.
DR VEuPathDB; FungiDB:ASPNIDRAFT2_1115863; -.
DR HOGENOM; CLU_000022_1_2_1; -.
DR Proteomes; UP000009038; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase 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:0009058; P:biosynthetic process; IEA:UniProt.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 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; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 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; 2.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 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; PS50075; CARRIER; 2.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1854
FT /note="PKS-NRPS hybrid synthetase ATPKS"
FT /id="PRO_0000452989"
FT DOMAIN 523..598
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1776..1851
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 24..423
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000250|UniProtKB:E9F8M3, ECO:0000255"
FT REGION 620..1057
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:E9F8M3, ECO:0000255"
FT REGION 1162..1496
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000250|UniProtKB:E9F8M3, ECO:0000255"
FT REGION 1536..1556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 558
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1811
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1854 AA; 199422 MW; 1088B2D13E4CACD7 CRC64;
MVPEDDQNLT DDPSKLGHNV VSLFDQTQTR YSPKAAIVCG EHTLTYGALA SDSDRLACLL
LSRGISRGHV VALALDRTPD LIMFILGVLK AGATYVPVDP ALPPERVNQM LDDEALRLVI
VSPVSTKGGA GTGRYDYGNK AVCCTTSELQ DQMRYQADKR PAVDIQPDDI AYILYTSGST
GKPKGVEIHH AAICNYALSV HQRPGCTDQD RVLFKSTISF DMAAFEIYVP LLCGATVVQA
QAHDIRDPRA LMHLIDRHSV TFSVATPTIL QMMLDSGWCG TPGFSKLVTG GEALSPRLAE
RLTACVEEVW NLYGPTETTA SVAAWKVQVG EDILIGTPNP NTRLYVLDAD LQPVPVGSTG
ELYISGAGVA RGYRNNPERT KAAFLPDPFW EGHTMYKSGD LACFLDSRRL AVIGRADTQI
KIRGQRIDPG DVEASITAHA DIANAVVVNR DERLVAYCIR KPGVGSAEVP LAKLLRPWLE
DRLPGYMVPS FFVEVDRFPS TLNGKVDLRA LPDPISTITP AKIPASTLTQ QLLAIWTDVL
GHGQIGMQDS FFHIGGNSAS IIQIQTKLEK LLGRPVPVPK LYEHFTIANL AAYLSDQTQT
NEVTEETKNP AGNDTTGEDI AVISMACRLP GDIHTPEELW KALISGTDAV TRVPEERWDA
DAIYDPDPEA RGKSYSTGGG FVRDAMDFDA QFFGISPREA RAIDPAQTMI LETCWEGFER
AGYGTKSLRG SQTGVFIGTG NSSVDDGQLS AAGTEKFEGH LGLGTAPSSL SGRVAYALGL
EGPTMTLDAG CAASLVATHV ACSALRQGEC DMAVAGGVTF LPSPGLHIEF SRIRVASPDG
RSRPFSADAA GMGLGEGASA VVLKRLSDAQ RDNDHIHAII RGSAVNHGGR GASMTAPSGP
GQKRVVRAAL AAARLKPYDI DYVEAHGTGT RLGDPVEASA LAEVFSSSRD DITGPLRIGS
SKSNIAHTQA AAGLAGLIKV ALAMQHTMLP QTLHSSQPSP LIDWVGGKLQ LLQRPMAWLP
RTNDPTAPRR AGINSFGLSG TNAHAIIEEP PRAHSNANGA DDDDNDDNAR LPLPLPFLLS
AYTSEALRQQ AQKLCNHLSS ATAQTKLSDV SYSLATTRTH FPRRIILAAQ DKTELMGRLA
SIIDNGVPAT ADNNKTARVA MLFSGQGTER ARMGKGLAER HLVFRNTVSH IAELFESVLE
KPLLDVMWAE PESEAASLLR RTDYAQPAIF TLQVALWRLW QSWGVQPAVV LGHSVGEIAA
AHVAGIMNLA DACRLVAARG KLMHALPESG SMVALEAGVD EVTSAIEQLS ARDRVSIASI
NTPTQVVASG EMDVIDKLAA YFEAQNRSSK ILKTSRAFHS HHLDESMLAL LRAVAETIVF
QEQTLPIVST VTGKLAEPGQ LSSADYWVRQ ARNPVLFAEG MQTLADQGAN CFVELGPAST
LCGMGASCLD GDLSQTSKVA GREGAKNLVW LHSLNPKSDD ALVIHNSLSD LHIRKVEIDW
AAFFKDIGGR RIQLPTYAFQ RHRYWLDGLR PIYSDKSSGQ PSGQSPSGCP QPTGQIQVGW
HTIDASSQYS NSTWGLLCPA SDAPWMSPVK EALLHAGKQP VTVNQLAEAK AMSGVLCFWE
SDSEDDMISK ASEQLQTVSR MKFSPWVVWV TRGAVGAGNM GEASLWGVMR SARVKYPQLC
LRIVDLEGDV NIATATKLCS ILMMSTEPEC VVLGERVLVP RMQFQMQAQV QEVQKHSKLC
VNGQETTNGA TAAADPNGTD SFENKIRMAG PEERAMMLQG LVRGITAKAL GVATAEEVDM
HQGFMDVGVG SLGAIQMRKE LSAQTGVKLP ANLTRVYPDP ISLSDALQKQ VEGQ
