ACUA_ASPA1
ID ACUA_ASPA1 Reviewed; 1749 AA.
AC A0A1L9WN37;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=6-methylsalicylic acid synthase acuA {ECO:0000303|PubMed:26374386};
DE Short=6MSAS {ECO:0000303|PubMed:26374386};
DE EC=2.3.1.165 {ECO:0000269|PubMed:26374386};
DE AltName: Full=Aculin biosynthesis cluster protein A {ECO:0000303|PubMed:26374386};
DE AltName: Full=Non-reducing polyketide synthase acuA {ECO:0000303|PubMed:26374386};
GN Name=acuA {ECO:0000303|PubMed:26374386}; ORFNames=ASPACDRAFT_1904397;
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, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26374386; DOI=10.1002/cbic.201500210;
RA Petersen L.M., Holm D.K., Gotfredsen C.H., Mortensen U.H., Larsen T.O.;
RT "Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus
RT Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A.";
RL ChemBioChem 16:2200-2204(2015).
CC -!- FUNCTION: 6-methylsalicylic acid synthase; part of the gene cluster
CC that mediates the biosynthesis of aculins (PubMed:26374386). The
CC pathway begins with the synthesis of 6-methylsalicylic acid by the
CC polyketide synthase (PKS) acuA via condensation of acetate and malonate
CC units (PubMed:26374386). The 6-methylsalicylic acid decarboxylase acuB
CC then catalyzes the decarboxylation of 6-methylsalicylic acid to yield
CC m-cresol (also known as 3-methylphenol) (Probable). These first
CC reactions occur in the cytosol (By similarity). The intermediate m-
CC cresol is then transported into the endoplasmic reticulum where the
CC cytochrome P450 monooxygenase acuC converts it to m-hydroxybenzyl
CC alcohol, which is further converted to gentisyl alcohol by the
CC cytochrome P450 monooxygenase acuD (Probable). Gentisyl alcohol is
CC further oxidized by the oxidoreductase acuE that probably catalyzes
CC hydroxylation of the aromatic ring (Probable). The aromatic system
CC might then be opened by oxidation through a Baeyer-Villiger type of
CC oxidation, which could be catalyzed by acuF, with the carboxylic acid
CC at C-1 subsequently reduced to an aldehyde by acuG (Probable).
CC Subsequently, a hemiacetal is formed, before the dehydrogenase acuH
CC would reduce the double bond between C-4 and C-6 (Probable). Finally,
CC keto-enol tautomerism results in formation of aculinic acid, which
CC exists as two diastereomers (both R/S configurations at C-1) by non-
CC enzymatic hemiacetal formation (Probable). The carboxypeptidase acuI
CC could be involved in the linking of aculinic acid to an aculene A
CC moiety produced by the aculene biosynthesis cluster and which leads to
CC the production of aculin A (Probable). AcuI may also be involved in the
CC attachment of proline to aculinic acid to form epi-aculins A and B
CC (Probable). {ECO:0000250|UniProtKB:A0A075TRC0,
CC ECO:0000269|PubMed:26374386, ECO:0000305|PubMed:26374386}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 3 H(+) + 3 malonyl-CoA + NADPH = 6-
CC methylsalicylate + 3 CO2 + 4 CoA + H2O + NADP(+);
CC Xref=Rhea:RHEA:12240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36658, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.165;
CC Evidence={ECO:0000269|PubMed:26374386};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12241;
CC Evidence={ECO:0000269|PubMed:26374386};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26374386}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A0A075TRC0}.
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:26374386}.
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DR EMBL; KV878982; OJJ97578.1; -; Genomic_DNA.
DR RefSeq; XP_020053918.1; XM_020198807.1.
DR AlphaFoldDB; A0A1L9WN37; -.
DR SMR; A0A1L9WN37; -.
DR STRING; 690307.A0A1L9WN37; -.
DR EnsemblFungi; OJJ97578; OJJ97578; ASPACDRAFT_1904397.
DR GeneID; 30972621; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_1904397; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0050641; F:6-methylsalicylic acid synthase activity; IEA:UniProtKB-EC.
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; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
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; 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; 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; 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; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Multifunctional enzyme; NADP; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1749
FT /note="6-methylsalicylic acid synthase acuA"
FT /id="PRO_0000450412"
FT DOMAIN 1671..1746
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..435
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 528..843
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 888..1160
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1169..1629
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT MOD_RES 1706
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1749 AA; 187960 MW; E8001C481487766A CRC64;
MACRVAGNNN NPEQLWQSLL QKKDASGEIP EMRWEPYLRR DSRNAKILKE TTSRGYFLDR
LEDFDGQFFG ISPKEAEQMD PQQRLSLEVT WEALENAGIT ARSLSGSDTA VFWGVNSDDY
SKLVLEDLPN VEAWMGIGTA YCGVPNRISY HLNLMGPSTA VDAACASSLV AVHHGVQAII
LGESKVAIVG GVNALCGPGL TRVLDKAGAV SSEGRCCSFD NDVKGYGRGE GAAAIVLKNL
SAAIKDGDHI MAVIKGTAVA QDGKTNGIMA PNAKAQQLVA HNALKVGNID PLTVGYVEAH
ATSTPLGDPT EVSAIAAVYG ADREPEAPCF IGSIKPNIGH LEAGAGAMGF IKAVMAVQKG
VLAPQANLTT LTKKIDWDNV GLKVVQQETK WPATDDVRRA AICSYGYGGT VSHAVIEQFN
FPETLDLKPG ASATNPTVLL LSGPQEKRLP IQARALRNWL QADGSQQDLQ RVAATLAVRR
DHHDYRAAIV VESKEDAIQA LGHLADGAND AWTSQSRVFG SGINRDVVWV FSGHGAQWAD
MGKELLQNPI FYQAVQPLDE IVEAEIGLSP IALLRSGEFE ASDHVQILTY IMQIGISAVL
HSHGVYPQAI IGHSVGEIAA SVVAGALTAE EGAVLITRRS VLYRQVMGQG GMILVNKPYA
EVAQELAGRE DLVVAIDSSP SSCVVAGSTE AVAEKAAEFK ERSIKTFTVR TDIAFHSPML
NQLVDPLMQS LEGSLAPTTP TRAKLYSTSL RDPRGSDLRD ATYWANNMVN PVHLTSAVQA
ALDDSYRVFL EVSSHPLVSH SINETIMDAG IEDYCMIPTL ARKKPSEKSI LHAVGQLHTR
GANVDWKSQL SGPWAGGLPN TSWMHKPTWR QIGAGPVSTS QTHDVEKHTL LGQRIGVAGT
DTVVYTTRLD NESKPFPGSH PLHGTEIVPA AGLVNTFVKA TGATVLNNVV LRVPVAINAP
RSVQIVAQRE DVKIMSRLIQ ENEGNNDDSS WVTHTTARWE SSSSSPVPAQ IDVEATKARI
GTRLRDEFSI DYLDKVGVSA MGFPWAVTEH YGNTKEMIAR VDAAPSVAAD AELPWDASSW
APILDAATSV GSTIFFNEPR LRMPAQIERV DIFTRANPPK VGWLYVQEAS DTALASHVSV
CDEAGNVVAK FTSMRFSEIE GTPGVSGSME SLVHQMAWPP AVPAEEPLPI NKLLLISQDV
PLREAYAATI SSSTQVTLLA NANDLIINRA ESLLTKETAI VYIPSQVSSL QDVPKSAETF
TWQLLELIKF VVNNALPVKI FVVTSNTGEG ETPTALAHAP LVGLSRVIAS EHPDQFGGLI
DTEVLTFPLT TMRYIQGADI IRIRDGVART MRLRSLPRHR LIQQQDQQQQ QPQLLPRPDG
TYLITGGLGA LGLEVADFLV TQGARRVILI SRRGLPPRRL WSKMEPSSPL APTITKILDL
EARGATIHVL PLDISQLTAA DALTTALDTL SLPPVRGVVH AAGVLDNELV LDTTPDAFAR
VLAPKITGGL VLNEVFPPQS VDFFILFSSC GQLVGFTGQS SYGAGNSFLD ALASHRQARG
DRGARAFQWT AWRALGMGAS TDFINAELAS KGITDVTADE AFAAWRHAAR YEGIDHAVVL
RALPLDADEP LPSPALADII VRRSASASAD SSPSSSPEKQ TIPTSGPELK AYLDKAIRGC
VAAVLHLPAA DEVDSKAALA DLGVDSVMTV TLRQKLQQAL RVKVPPTLTW SHPTVGHLVG
WFAEKVGKE
