AR283_ARTOA
ID AR283_ARTOA Reviewed; 1761 AA.
AC G1XU04;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=6-methylsalicylic acid synthase {ECO:0000303|PubMed:26422178};
DE Short=6-MSAS {ECO:0000303|PubMed:26422178};
DE EC=2.3.1.165 {ECO:0000269|PubMed:26422178};
DE AltName: Full=Arthrosporol biosynthesis cluster protein AOL_s00215g283 {ECO:0000303|PubMed:26422178};
GN ORFNames=AOL_s00215g283;
OS Arthrobotrys oligospora (strain ATCC 24927 / CBS 115.81 / DSM 1491)
OS (Nematode-trapping fungus) (Didymozoophaga oligospora).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Orbiliomycetes;
OC Orbiliales; Orbiliaceae; Orbilia; Orbilia oligospora.
OX NCBI_TaxID=756982;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24927 / CBS 115.81 / DSM 1491;
RX PubMed=21909256; DOI=10.1371/journal.ppat.1002179;
RA Yang J., Wang L., Ji X., Feng Y., Li X., Zou C., Xu J., Ren Y., Mi Q.,
RA Wu J., Liu S., Liu Y., Huang X., Wang H., Niu X., Li J., Liang L., Luo Y.,
RA Ji K., Zhou W., Yu Z., Li G., Liu Y., Li L., Qiao M., Feng L., Zhang K.-Q.;
RT "Genomic and proteomic analyses of the fungus Arthrobotrys oligospora
RT provide insights into nematode-trap formation.";
RL PLoS Pathog. 7:E1002179-E1002179(2011).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=26422178; DOI=10.1021/acs.jafc.5b04244;
RA Xu Z.F., Wang B.L., Sun H.K., Yan N., Zeng Z.J., Zhang K.Q., Niu X.M.;
RT "High trap formation and low metabolite production by disruption of the
RT polyketide synthase gene involved in the biosynthesis of arthrosporols from
RT nematode-trapping fungus Arthrobotrys oligospora.";
RL J. Agric. Food Chem. 63:9076-9082(2015).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27723963; DOI=10.1021/acs.jafc.6b03241;
RA Xu Z., Chen Y., Song T., Zeng Z., Yan N., Zhang K., Niu X.;
RT "Nematicidal key precursors for the biosynthesis of morphological
RT regulatory arthrosporols in nematode-trapping fungus Arthrobotrys
RT oligospora.";
RL J. Agric. Food Chem. 64:7949-7956(2016).
RN [4]
RP FUNCTION.
RX PubMed=28475838; DOI=10.1021/acs.jafc.7b01290;
RA Song T.Y., Xu Z.F., Chen Y.H., Ding Q.Y., Sun Y.R., Miao Y., Zhang K.Q.,
RA Niu X.M.;
RT "Potent nematicidal activity and new hybrid metabolite production by
RT disruption of a cytochrome P450 gene involved in the biosynthesis of
RT morphological regulatory arthrosporols in nematode-trapping fungus
RT Arthrobotrys oligospora.";
RL J. Agric. Food Chem. 65:4111-4120(2017).
CC -!- FUNCTION: 6-methylsalicylic acid synthase; part of the gene cluster
CC that mediates the biosynthesis of arthrosporols, metabolites that
CC possess a novel hybrid carbon skeleton consisting of a polyketide-
CC derived epoxycyclohexenol combined with a terpenoid-derived monocyclic
CC sesquiterpenol substructure. Arthrosporols B and C are two dehydration
CC derivatives of arthrosporol A. All of the arthrosporols shared the same
CC epoxycyclohexenol moiety, and the difference among them only occurred
CC in the monocyclic sesquiterpenol substructure (PubMed:26422178,
CC PubMed:27723963). The pathway begins with the biosynthesis of 6-
CC methylsalicylic acid (6-MSA), the first precursor of the polyketide-
CC derived epoxycyclohexenol in arthrosporols, by the polyketide synthase
CC (PKS) AOL_s00215g283 via condensation of 1 acetate and 3 malonate
CC units. AOL_s00215g283 performs a series of programmed reactions
CC including Claisen condensation, dehydration, reduction, and cyclization
CC to yield 6-MSA (PubMed:26422178). The 6-methylsalicylic acid
CC decarboxylase AOL_s00215g281 then catalyzes the decarboxylation of 6-
CC methylsalicylic acid to yield m-cresol (PubMed:27723963). The
CC arthrosporols precursor m-cresol might be a versatile precursor for
CC other pathways (PubMed:27723963). The cytochrome P450 monooxygenase
CC AOL_s00215g282 then acts as a m-cresol hydrolase that converts m-cresol
CC to arthrosporols, in combination with other arthrosporols cluster's
CC enzymes such as the cytochrome P450 AOL_s00215g280 (PubMed:27723963,
CC PubMed:28475838). {ECO:0000269|PubMed:26422178,
CC ECO:0000269|PubMed:27723963, ECO:0000269|PubMed:28475838}.
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:26422178};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12241;
CC Evidence={ECO:0000269|PubMed:26422178};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26422178}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of arthrosporol A
CC (PubMed:26422178, PubMed:27723963). Displays significant increases in
CC the trap formation and the nematicidal activity (PubMed:26422178).
CC {ECO:0000269|PubMed:26422178, ECO:0000269|PubMed:27723963}.
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DR EMBL; ADOT01000316; EGX43547.1; -; Genomic_DNA.
DR RefSeq; XP_011127787.1; XM_011129485.1.
DR AlphaFoldDB; G1XU04; -.
DR SMR; G1XU04; -.
DR STRING; 13349.G1XU04; -.
DR EnsemblFungi; EGX43547; EGX43547; AOL_s00215g283.
DR GeneID; 22898694; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_35_3_1; -.
DR InParanoid; G1XU04; -.
DR OMA; HRRFWRT; -.
DR OrthoDB; 19161at2759; -.
DR PHI-base; PHI:5276; -.
DR Proteomes; UP000008784; Unassembled WGS sequence.
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: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: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; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
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; 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 SMART; SM00827; PKS_AT; 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.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1761
FT /note="6-methylsalicylic acid synthase"
FT /id="PRO_0000445288"
FT DOMAIN 1686..1761
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:26422178"
FT REGION 21..446
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26422178"
FT REGION 554..870
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26422178"
FT REGION 918..1187
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26422178"
FT REGION 1399..1587
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26422178"
FT REGION 1654..1680
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 190
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 641
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1721
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1761 AA; 190417 MW; 888A70565BBB315A CRC64;
MTSTPATSLG DMDHEYNQDD IAIIGMACRL AGGIQSIEQF WNAILSKKDA SGEIPEMRWE
PYFRRDSRNA EILKKTTSRG YFLDRLENFD ASFFGISPLE AELMDPQQRI ALEVTWEALE
HAGISVTSLA GSDTAVFMGV NSDDYSRLLL EDVPGVEAWM GIGTAFCGIP NRISYTLDLH
GPSTAVDAAC ASGLVAVHHG RQALLAGESK LAIVGGVNAL IGPGLTRVLD EAGAVTPEGR
CRSFDDSASG YGRGEGASVL VLKRLSEAII DGDKVLAVLK GSAVGQDGKT NGIMSPNQVA
QEEVARKALS VARVDPLSVA FVEAHATSTP VGDPCEVAAI ASVYGSGAGR PKDLPCKIGS
VKPNVGHLEA GAGSTSLIKA VLAVSNGIFP PQANFQTPNR KMDWDNNSLE VIRGVSDWVQ
DRKRAGICSY GYGGTVAHAV IEQAPAPNFG PEDQVGDVVY ADAAPYLLFW SAPQSQRLRE
TAAQLASWVG ETEQPLADIA NTLAYRRSQH QHRCAVVADN REEAVKLLEL GSQNADSPWM
IKEKVSNYGK KGAVWVFSGH GAHWTDMGKE LLASEPAFYG AVSSIDNIVR DILNFSPLEA
LENGDLKTTD KQQVLTYAMQ VGLSAVLRSK GAQPAAVIGH SVGEIAASVT AGCLTIQEGA
FIVSQRAKLY RLVAGRGAMI LVDLSPEDAV KELEEQGQTG AVAVAIHSSP NTCVLSGGIE
AINELEQSLK DKHIQARRVK TDVAFHSPVL NELAEPLLEL ISGHIKPQQP KIRLYSTSLT
QARGDNLRDE KYWIDNMIQP VLLTNAVKAA LEDDFGIFLE VSSHPIIAHS INETIIEADS
DGVIFPTLRR DKPSRKCILF ALGKLHCHGA PIDLRANFSG DWTRDVPTTV WKHNPFWRKV
GTGSLQPNKS VTHDVKSHVL LGAKHQVVGS DTTMWTTTLD ESTRPFPGSH PLHGTEIVPA
AVLLNTFLHT GEEYNALKDV ILRVPVAMSA PRNIQIVKEQ GRVRIVSRLQ ASEGENNNTE
SSWLTHTTGH VANNEWSKSS LDISATKKKL PSVKPSFATD YLASVGVPDM GFPWKVTEHY
GEGDEMLSRV DTAPESSEKS IPWDVSSWAP ILDAATSIGS SIFYKEPVLR MPAQIDEVAI
TPGSIPKVAY IHTTVETGMW RVNVAILNEE GHEVAHINGM RFSAVEGTPG ASGSVESLVH
QMSWPPAKLE EEGFQLKNVV FVSEQSDRVA AYIQDLQKRK VSTTVVPNPA GLEEQNLSSE
GTIVAYLPSG SDLEEDTAKF SSTFCSEVLD IAKLLVNQKS PSKLWCITQG LFEAFSPSSL
SQGPLVGLSR IIASEHPEVW GGLVDTDDES FPLQAVKYVK SVDVISVRDS VARVARLRPV
PRSKIVTGRE KTFTPTAEGT YLITGGLGAL GLETAKWMVE SGARRLILVS RRGLPPRRKW
VDSNDDSAIS TIRKLERLGA SIHVVAADIS KPDGAERLEQ ALDLLDLPSI SGVVHAAGVL
EDQLVAETTK ESFDRVLAPK VSGAMALHQL FPPKTLEFFV LFSSCGQLLG FPGQASYASG
NAFLDTFADF RRNQGDNIVS FLWTSWNGLG MASSTEYINA ELEAKGITSV SRDEAFRAWE
HAIKHDIHQA VVLRALPVEE NGIPPLPILD EIAPRKRAES SGTEAVSKGE VSEKAPVPKS
GPELKEYLQN AISECVAKTL RLPSAADVDP STALTEMGMD SVMTVSLRKH LQTSLKVTVP
PTLIWGHPTV NHLVKWFEEK I
