YANA_ASPNA
ID YANA_ASPNA Reviewed; 1779 AA.
AC G3Y419;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=6-methylsalicylic acid synthase {ECO:0000303|PubMed:24684908};
DE Short=6MSAS {ECO:0000303|PubMed:24684908};
DE EC=2.3.1.165 {ECO:0000269|PubMed:24684908};
DE AltName: Full=Non-reducing polyketide synthase yanA {ECO:0000303|PubMed:24684908};
DE AltName: Full=Yanuthone D biosynthesis cluster protein A {ECO:0000303|PubMed:24684908};
GN Name=yanA {ECO:0000303|PubMed:24684908};
GN Synonyms=pks48 {ECO:0000303|PubMed:24684908}; ORFNames=ASPNIDRAFT_44965;
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 BIOTECHNOLOGY.
RX PubMed=11031048; DOI=10.1021/jo0006831;
RA Bugni T.S., Abbanat D., Bernan V.S., Maiese W.M., Greenstein M.,
RA Van Wagoner R.M., Ireland C.M.;
RT "Yanuthones: novel metabolites from a marine isolate of Aspergillus
RT niger.";
RL J. Org. Chem. 65:7195-7200(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24684908; DOI=10.1016/j.chembiol.2014.01.013;
RA Holm D.K., Petersen L.M., Klitgaard A., Knudsen P.B., Jarczynska Z.D.,
RA Nielsen K.F., Gotfredsen C.H., Larsen T.O., Mortensen U.H.;
RT "Molecular and chemical characterization of the biosynthesis of the 6-MSA-
RT derived meroterpenoid yanuthone D in Aspergillus niger.";
RL Chem. Biol. 21:519-529(2014).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of yanuthone D, a fungal isoprenoid
CC epoxycyclohexenone that acts as an antibiotic against fungi and
CC bacteria (PubMed:24684908). The first step of the pathway is the
CC synthesis of 6-methylsalicylic acid (6-MSA) by the polyketide synthase
CC yanA (PubMed:24684908). 6-MSA is then converted to m-cresol by the
CC decarboxylase yanB (PubMed:24684908). The cytochrome P450 monooxygenase
CC yanC then catalyzes the oxidation of m-cresol to toluquinol
CC (PubMed:24684908). Epoxidation of toluquinol is then performed by the
CC short chain dehydrogenase yanD, with the help of yanE, and a further
CC prenylation by yanG leads to 7-deacetoxyyanuthone A (PubMed:24684908).
CC The next step is the hydroxylation of C-22 of 7-deacetoxyyanuthone A by
CC the cytochrome P450 monooxygenase yanH to yield 22-deacetylyanuthone A
CC (PubMed:24684908). O-Mevalon transferase yanI then attaches mevalon to
CC the hydroxyl group of 22-deacetylyanuthone A to produce yanuthone E
CC (PubMed:24684908). Finally, the FAD-dependent monooxygenase yanF
CC oxidizes the hydroxyl group at C15 of yanuthone E to form yanuthone D
CC (PubMed:24684908). Furthermore, several branching points in the pathway
CC lead to the production of yanuthones F and G from 7-deacetoxyyanuthone
CC A; yanuthones H and I from 22-deacetylyanuthone A; and yanuthone J from
CC yanuthone E (PubMed:24684908). {ECO:0000269|PubMed:24684908}.
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:24684908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12241;
CC Evidence={ECO:0000269|PubMed:24684908};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:24684908}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DISRUPTION PHENOTYPE: Loses the ability to produce yanuthones D and E
CC (PubMed:24684908). {ECO:0000269|PubMed:24684908}.
CC -!- BIOTECHNOLOGY: Yanuthone D is an antibiotic against C.albicans,
CC methicillin-resistant S.aureus (MRSA), and vancomycin-resistant
CC Enterococcus (PubMed:11031048). {ECO:0000269|PubMed:11031048}.
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; ACJE01000012; EHA22196.1; -; Genomic_DNA.
DR AlphaFoldDB; G3Y419; -.
DR SMR; G3Y419; -.
DR STRING; 380704.G3Y419; -.
DR PRIDE; G3Y419; -.
DR EnsemblFungi; EHA22196; EHA22196; ASPNIDRAFT_44965.
DR VEuPathDB; FungiDB:ASPNIDRAFT2_1123159; -.
DR HOGENOM; CLU_000022_35_3_1; -.
DR BRENDA; 2.3.1.165; 518.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000009038; 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:0008168; F:methyltransferase 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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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; 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; 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 Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1779
FT /note="6-methylsalicylic acid synthase"
FT /id="PRO_0000436664"
FT DOMAIN 1703..1777
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 43..416
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 586..883
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 942..1218
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1384..1506
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 215
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 672
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1737
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1779 AA; 190967 MW; 0854FD515190DD11 CRC64;
MSASRSSTKF STPAEGSDNG KEFTTPATST EGHEVPDRPG DALADVAIIG MACRTPGDVR
SPDSLWQYLL KKGDASGSLP DWRWEPYRQR HPRNAALLAQ TTAKGYFLDD IDHFDAAFFS
ISPREAEQMD PQQRLALEVA WEALENAGIS PPQLAGSNTS VYMGVNSDDY AKLLLEDLPN
VDAHMGVGTA YCGIPSRISY ILDLMGPSVA LDAACASSLV AVHHARQAIR AGETDLAIAG
GVNALLGPGL TRVLDEAGAI STDGKCRSFD ETASGYGRGE GAGVVILKRL DKALADGDHV
LAVLKGSAVA SDGKTLGIMA PNARAQLLVA QKALAEAKVS ADSINYVEAH ATSTSLGDPT
ETNALAEVYG AGSGRSPSDP CYIGSIKPNI GHLEAGAGVM GLIKAVLVLR HGQVPPQANL
KTLNSKIAWN ENLLCPPREL VTLPCPGPIH PLRAAVASYG YSGTVSHAVL EAFAGHSEFA
ERLSQIPTGD DPSPVLLLIS APQARRVSAA AGALKQWLSE NEASISLKTV SSTLAQRRAH
HRYRHAIVAD SVPDAIAALD DVSKEAPNRW VIKDKIDSKA AKGPVWIFSG HGAQWADMGR
ELFESSPAFE EVVRNLEPII QDEVGFSAIE TLQKGCPDRS DVVQVMTFLM HLGIAAVLEI
ESGPPSAVVG HSLGEAAAAV VSGALTWREG ALVVCRRARL YRELMGQGAM ALVRVSAEEA
RTRIGRQTGV WVAIETSPSA CVLSGEVDAI KQLSDRWREE GIEVRMVASD VPFHTPMLER
LAKPLYESLR GELHPRVPNR ALFSTSQPDP RSEVLRDAQY WVTNMIQPVR LQSAIAAIAQ
DGFRALVEVS SHPIVTHSVV ETMGECTEDP VLVTPTMVRR QPALKSILAA TGRLHCFGCA
IKFIELDPNA PWNSSVPSTV WHHQPFYRAV SQTSASSQLE TTHDPAANNL LGKRIALWGT
EEVLYQTRLE EENRPFPGHH PLHGSEIVPA AVLLRTFLQA LTPRCVEQVS LQVPVVVSPA
RKVQIRHNTR NITITSCLEE SSSQEDGSWL VNTTAAVGAA NVVPSQSRMD LSELRKRLPQ
KLADSFSIDY LASVGVSAMG FPWQVTHHVA SDDEMLARVD ANPDNMGGMN DFLTSLMDAA
TSISSTLWHR QPLLRMPTSV RRVVAVHEIP IPRVVYIHCT KVASTSECTA DVTLTGEDGT
VLMEIQGMSF AGLEGESFSR KSTAGLVHQI QWPPAALVED PSEFSHIAFV TPDITDPRLE
QYQSQLDALA ITSSVHQAAS DLPLTSHTSL AVVYLPQTMT DVFDTATRSC NDLVSIIQTI
TAAASSTTRV FVLTAGTELG HSALLGLSRI IQAEHPDIWG SLIEVEDTFS LPLMAMRYVR
DADVIRIKDG VPRIARLRPL PSASSSLTPL TFSPASTYLI TGGLGALGLS VAHWMVTQGA
RRLLLLSRRA LPPRSTWSST HMNNPTIQSI LALERLGATV HCLPIDISLP MAASGLRSTL
ETLNLPSVAG VIHAAGIVSD QLVEQVTPDV LESVLAPKIK GALNLHDVFP PASLDFFVLF
SSCGQLLGFP GQASYASGNA FLDGLARSRR AQGDNAISLL WTTWRGMGMG QSANGAMEAE
LYARGITDIT PDEAFRAWSA VASTGGGGTD HAVIVRARVL EGGEPLPHPI LTDIATRKAE
VVNAGEHPAG SQEVKLSGRE LEQHLRDVIN GCVSKTLSVK EDEIDDAVAL AEMGMDSVMT
VNFRMTLQQT LKVPVGPTLI WKCPTVQHLV KHFTKELDA
