ACRA_ASPA1
ID ACRA_ASPA1 Reviewed; 2429 AA.
AC A0A1L9WQM9;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Highly reducing polyketide synthase acrA {ECO:0000303|PubMed:32234543};
DE EC=2.3.1.- {ECO:0000269|PubMed:32234543};
DE AltName: Full=Acurin A biosynthesis cluster protein A {ECO:0000303|PubMed:32234543};
GN Name=acrA {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_48;
OS Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=690307;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT "Comparative genomics reveals high biological diversity and specific
RT adaptations in the industrially and medically important fungal genus
RT Aspergillus.";
RL Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN [2]
RP FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, PATHWAY, AND INDUCTION.
RX PubMed=32234543; DOI=10.1016/j.fgb.2020.103378;
RA Wolff P.B., Nielsen M.L., Slot J.C., Andersen L.N., Petersen L.M.,
RA Isbrandt T., Holm D.K., Mortensen U.H., Noedvig C.S., Larsen T.O.,
RA Hoof J.B.;
RT "Acurin A, a novel hybrid compound, biosynthesized by individually
RT translated PKS- and NRPS-encoding genes in Aspergillus aculeatus.";
RL Fungal Genet. Biol. 139:103378-103378(2020).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the cluster that
CC mediates the biosynthesis of acurin A, a highly reduced polyketide
CC coupled to a serine via a peptide bond (PubMed:32234543). The
CC activities of the highly reducing polyketide synthase acrA and the
CC nonribosomal peptide synthetase acrB are collectively responsible for
CC the synthesis of the acurin A core structure with a heptaketide
CC backbone produced by acrA covalently fused to a L-serine by acrB
CC (PubMed:32234543). After the formation of the PK-NRP hybrid product, it
CC is detached from acrB by reductive release to set up the formation of
CC the lactam ring by aldol condensation (Probable). The hydrolyase acrC
CC then catalyzes water loss to generate a double bond in the ring
CC (Probable). This double bond is probably reduced, which is followed by
CC three oxidations at C-22 to generate the carboxylic acid moiety,
CC involving probably the FAD-binding monooxygenase acrE and the
CC cytochrome P450 monooxygenases acrD and acrF (Probable). Finally, a
CC last methylation step performed by the O-methyltransferase acrG leads
CC to the production of acurin A (Probable). {ECO:0000269|PubMed:32234543,
CC ECO:0000305|PubMed:32234543}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:32234543}.
CC -!- INDUCTION: Expression is positively regulated by the acurin A cluster-
CC specific transcription regulator acrR. {ECO:0000269|PubMed:32234543}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase (MT)
CC domain responsible for the incorporation of methyl groups; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:32234543}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of acurin A.
CC {ECO:0000269|PubMed:32234543}.
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DR EMBL; KV878980; OJJ98486.1; -; Genomic_DNA.
DR RefSeq; XP_020054826.1; XM_020202047.1.
DR AlphaFoldDB; A0A1L9WQM9; -.
DR SMR; A0A1L9WQM9; -.
DR EnsemblFungi; OJJ98486; OJJ98486; ASPACDRAFT_48.
DR GeneID; 30975861; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_48; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase 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:0032259; P:methylation; 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; -; 1.
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; 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; IPR013217; Methyltransf_12.
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; IPR029063; SAM-dependent_MTases_sf.
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; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
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; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
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 PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2429
FT /note="Highly reducing polyketide synthase acrA"
FT /id="PRO_0000450413"
FT DOMAIN 2351..2428
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:32234543"
FT REGION 7..439
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT REGION 541..861
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT REGION 931..1229
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT REGION 1388..1577
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT REGION 2065..2235
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT MOD_RES 2388
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2429 AA; 263753 MW; 2DDD4445E9C160F8 CRC64;
TGTPEPIAIV GMGCRFPGGA NTPSKLWDLL CAKRDVQRRI PTDRFHVDAF YDRDGERAGC
LNVREAYTLD EDIRQFDAAF FKTNALEAEA MDPQQRLLLE TVYEALESAG GVMEDLHGSD
TAVYVGVMTG DYHELLLRDP EDMPKYMATG TARSILSNRI SYFFDWTGPS MTIDTACSSS
LVAVHEAVQA LRQGRSTLAC AAGANLILGP EMMISESKLH MLSPTGRSRM WDAGADGYAR
GEGFAAVMLK TLSQAVADGD YVYGVIRETG VNSDGRTNGI TLPGADSQTA LIRQTYARAG
LDIDSQRCQY FEAHGTGTAA GDPIEARAIY NAFFASSSEQ AETPLYVGSV KTAVGHLEGT
AGLAGLVKAV EAVRRGVIPP NMLFESLNPE IQPFYHRLAV PTDTIPWPEV REGEPRRASV
NSFGFGGTNA HAIIESYDNP HRRPSSATSS LYTPLVLSAN SESSLRGQVE ALHAFLSTTD
TPVQHILHTL QTRRSQHPVR ATFSAPDRDT LSTALSKAVA SDSTLGTRVD KRPAKPRILA
VFTGQGAQWP TMGREILRAS PLAQRTLSTL QSALDTLPDG PDWLLSTEIL ADKDTSRLAS
ASVAQPLCTA VQILVVDLLR LAGITPSVVV GHSSGEIAAA YAAGMISAAE AIRIAYYRGV
HASLARGQNG QRGGMMAVGM SYDEATEFCE ENFAERIEVA ASNAPSSVTL SGDEDAIAEA
KAILDERGVF ARPLRVDTAY HSAHMIPCSE PYLDSLAACE IAPQEAREGC VWVSSVHGAR
MEGYRVDTLT GEYWNDNMVS PVMFSTAVEM ALSEEAACDV AIEIGAHPAL KGPFTQTAKQ
VAAAASSATP LPYSGTLSRG QHDIEALSET LGYLWLHLGA KAVAFPAYTS AFTDALPQWV
PDLPRYSWDH RQSFWRESTK SANFRSRLPR HPLLGVRSTE DLDQEMRWAI TLRTQELPWL
EGHKVEGQVI YPAAAYLVMA MEAAHNLVGE GLSVQMLELF DVEIANAIPL PEDGKGVEVQ
FTLVPSPGNA KSETKTAQWA CYARTAGTGK SSWRSNARGT VRVVLGPAAD EDLPPRNPPT
GVFHEVKTER FYEALTAIGL HYTGPFRGLD SVHRRSGTAM ATATQIPAAE LGVPIHPAVL
DAAFQTLFAA YCWPEDGSLR APFVPTGLQS LRIVNRDLVQ ASAQLTVDAA ITHSSGTTII
ADLDLYSPAA AGLIQLQGLR CSSLTPPGPR DYKELYTQTA WEVDLSSGLA ALSSVSDSDS
PSNLALVDLS ERLAYYYLRH LNTTIPRSAV PQMEWHHQRI FEWIDHLFPL VTSGKHPTIR
PEWSTDTKPH LLALASQYPD SVDLQLIRAV GEHLPAVVRG EAWMLEHMVA NDTLDRFYKF
GLGFARANGY MGRVAGQIAH RYPRSRILEI GAGTGGATKG ILEALDGRFE RYTFTDISTG
FFEAAATQFE RWAGKMSYRA LDVEKELSSQ GWDGEEAGFD VIVASNVLHA TKSLRKTMEN
VRRLLKPGGF LLLLEVTSEI VRVKLMMAGL PGWWLGGEDG RRYGPTITVE QWDTLLKETG
FAGVDHVVND FVDESKYMTS VMVTQAVDAD VRLLREPLSA GWTLPPVTVV GGQKGLAGRV
VEALGSAGSV QLVENLEGLF VQPDISVTSL VILEDFDHPV LEDFTPCKLE ALQRALPECR
QLLWVSGQCR EKNPYGNMAI GLCRAIAAEQ PHIQFQHLDI EDAVDAGAAK AVTEALVRLV
FASQTRLATK NVLWTCEPEL VRENGQWLVP RIVPDKRLND QLNARKMVVQ GMATSEEKLE
LVKQAERYVL SPALPSVVEK DGAVEVKVTH ALVNAVQLDQ GSVCVVSGNL LSKPDVQVIA
CTNSVRSVVT VSEEMVFPAE NASPPLLQTV AFGLVADEWL HGLSSSDVLV LHQADEQLGR
VLRSKAAEAG VKVVDVRTHA YASERSIRAQ IPPSTKLLVD FAQSSVQWER ILPAQCKIRS
YGDAIAPGTS IADTANLNTS QLQRAISWAQ QQQPADTALE TIPAAELATT PTPSYHAILS
FSPSTTIPTI TRPVNPALLF RPDRTYLLVG CTGGLGQSLC RWMVLNGARH LALTTRNRTR
ISTTWLADLA QLGANVQLFE ADVADMASLT AIHQTITTGM PPIAGIANAA MVLSDRSFGE
LKHTDFTTVF GPKVLGTKNL DTLFHSQKLD FFIMFSSLAS IVGNRGQSNY VAANLFMSTV
AAQRRARGLA ASVFHIGMVL GVGYVSTTGV YETTLRQYKY MPIAEPEFWD MFAQAIVIGH
PTLAGGHAPE MITGLHRHSL REEVAKAFWA ENPRFSLHTL VEESQTVVVD AASAKQVPLA
EAVAEAETLE EVDGVIQEAF VVKMERMLQA AKGSIERGQP LINLGVDSLI AVEIRSWFLK
ELEVDMPVLK LVGGMSVGEL CREAASEVL
