ORSA_EMENI
ID ORSA_EMENI Reviewed; 2103 AA.
AC Q5AUX1; C8V4V0;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Orsellinic acid synthase {ECO:0000303|PubMed:19666480};
DE Short=OAS {ECO:0000303|PubMed:19666480};
DE EC=2.3.1.- {ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687};
DE AltName: Full=Non-reducing polyketide synthase orsA {ECO:0000303|PubMed:20174687};
DE AltName: Full=Orsellinic acid/F9775 biosynthesis cluster protein A {ECO:0000303|PubMed:19666480};
GN Name=orsA {ECO:0000303|PubMed:19666480}; ORFNames=AN7909;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP INDUCTION.
RX PubMed=19448638; DOI=10.1038/nchembio.177;
RA Bok J.W., Chiang Y.M., Szewczyk E., Reyes-Dominguez Y., Davidson A.D.,
RA Sanchez J.F., Lo H.C., Watanabe K., Strauss J., Oakley B.R., Wang C.C.,
RA Keller N.P.;
RT "Chromatin-level regulation of biosynthetic gene clusters.";
RL Nat. Chem. Biol. 5:462-464(2009).
RN [4]
RP IDENTIFICATION OF THE ORS CLUSTER, INDUCTION, FUNCTION, DISRUPTION
RP PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19666480; DOI=10.1073/pnas.0901870106;
RA Schroeckh V., Scherlach K., Nuetzmann H.W., Shelest E., Schmidt-Heck W.,
RA Schuemann J., Martin K., Hertweck C., Brakhage A.A.;
RT "Intimate bacterial-fungal interaction triggers biosynthesis of archetypal
RT polyketides in Aspergillus nidulans.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14558-14563(2009).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, DOMAIN, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20174687; DOI=10.1039/b904541d;
RA Sanchez J.F., Chiang Y.M., Szewczyk E., Davidson A.D., Ahuja M.,
RA Elizabeth Oakley C., Woo Bok J., Keller N., Oakley B.R., Wang C.C.;
RT "Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of
RT Aspergillus nidulans.";
RL Mol. Biosyst. 6:587-593(2010).
RN [6]
RP INDUCTION.
RX PubMed=23892751; DOI=10.1128/aem.01578-13;
RA Nuetzmann H.W., Fischer J., Scherlach K., Hertweck C., Brakhage A.A.;
RT "Distinct amino acids of histone H3 control secondary metabolism in
RT Aspergillus nidulans.";
RL Appl. Environ. Microbiol. 79:6102-6109(2013).
RN [7]
RP INDUCTION.
RX PubMed=23841751; DOI=10.1111/mmi.12326;
RA Bok J.W., Soukup A.A., Chadwick E., Chiang Y.M., Wang C.C., Keller N.P.;
RT "VeA and MvlA repression of the cryptic orsellinic acid gene cluster in
RT Aspergillus nidulans involves histone 3 acetylation.";
RL Mol. Microbiol. 89:963-974(2013).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of orsellinic acid, as well as of the
CC cathepsin K inhibitors F9775 A and F9775 B (PubMed:19666480,
CC PubMed:20174687). The non-reducing polyketide synthase orsA produces
CC orsellinic acid by condensing acetyl-CoA with 3 malonyl-CoA units
CC (PubMed:19666480, PubMed:20174687). Further modifications by the
CC decarboxylase orsB and the tyrosinase-like protein orsC lead to the
CC production of F9775 A and F9775 B (PubMed:20174687). The functions of
CC orsD and orsE remain unclear since only orsB and orsC are required to
CC convert orsellinic acid into F9775 A and F9775 B (PubMed:20174687).
CC {ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 2 H(+) + 3 malonyl-CoA = 3 CO2 + 4 CoA +
CC orsellinate; Xref=Rhea:RHEA:62972, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16162, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384;
CC Evidence={ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62973;
CC Evidence={ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687}.
CC -!- INDUCTION: Expression is induced by an intimate physical interaction of
CC the fungal mycelia with the bacterium Streptomyces hygroscopicus
CC (PubMed:19666480). Expression is repressed by VeA and MvlA via histone
CC 3 acetylation by the SAGA/ADA complex (PubMed:23892751,
CC PubMed:23841751). {ECO:0000269|PubMed:19666480,
CC ECO:0000269|PubMed:23841751, ECO:0000269|PubMed:23892751}.
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 -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein (By similarity).
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of orsellinic acid,
CC lecanoric acid and F-9775A/B (PubMed:19666480, PubMed:20174687).
CC {ECO:0000269|PubMed:19666480, ECO:0000269|PubMed:20174687}.
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DR EMBL; BN001302; CBF73505.1; -; Genomic_DNA.
DR EMBL; AACD01000135; EAA59563.1; -; Genomic_DNA.
DR RefSeq; XP_681178.1; XM_676086.1.
DR AlphaFoldDB; Q5AUX1; -.
DR SMR; Q5AUX1; -.
DR STRING; 162425.CADANIAP00003928; -.
DR ESTHER; emeni-q5aux1; Thioesterase.
DR PRIDE; Q5AUX1; -.
DR EnsemblFungi; CBF73505; CBF73505; ANIA_07909.
DR EnsemblFungi; EAA59563; EAA59563; AN7909.2.
DR GeneID; 2868938; -.
DR KEGG; ani:AN7909.2; -.
DR VEuPathDB; FungiDB:AN7909; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_4_1; -.
DR InParanoid; Q5AUX1; -.
DR OMA; TFHDDAD; -.
DR OrthoDB; 68112at2759; -.
DR BioCyc; MetaCyc:MON-21843; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0022900; P:electron transport chain; IEA:GOC.
DR GO; GO:1900557; P:emericellamide biosynthetic process; IMP:AspGD.
DR GO; GO:1900611; P:F-9775A biosynthetic process; IMP:AspGD.
DR GO; GO:1900614; P:F-9775B biosynthetic process; IMP:AspGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:1900815; P:monodictyphenone biosynthetic process; IMP:AspGD.
DR GO; GO:1900584; P:o-orsellinic acid biosynthetic process; IMP:AspGD.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR GO; GO:0045461; P:sterigmatocystin biosynthetic process; IMP:AspGD.
DR GO; GO:1900590; P:violaceol I biosynthetic process; IMP:AspGD.
DR GO; GO:1900593; P:violaceol II biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
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; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..2103
FT /note="Orsellinic acid synthase"
FT /id="PRO_0000438572"
FT DOMAIN 1640..1716
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1741..1815
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 17..232
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:20174687"
FT REGION 351..785
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:20174687"
FT REGION 881..1197
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:20174687"
FT REGION 1303..1579
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:20174687"
FT REGION 1592..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1722..1743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1809..1838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1849..2082
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:20174687"
FT COMPBIAS 1612..1638
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1727..1742
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 525
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 973
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1676
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1775
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2103 AA; 225849 MW; 24941E20ABF74DB1 CRC64;
MAPNHVLFFP QERVTFDAVH DLNVRSKSRR RLQSLLAAAS NVVQHWTASL DGLERADIGS
FEDLVELAER QTTQTRGSIV ADLVLLTTVQ IGQLLVLAED DPAILSGHAG ARAIPMGFGA
GLVAAGVAAA ATSADGIVNL GLEAVSVAFR LGVELQRRGK DIEDSNGPWA QVISSATTIA
DLEQALDRIN ASLRPINQAY IGEVMTESTV VFGPPSTLDA LAKRPELAHA TITSPASALA
QVPLHGAHLP PISATMIAAS SSQQATELWK LAVEEVANKP IDVHQAVTAL IHDLHRANIT
DIVLTAIGAS TETSGIQSLL EKNGLAVELG QLSPTPRPYG NDLDSIPADA IAVVGMSGRF
PNSDTLDEFW RLLETATTTH QVIPESRFNV DDFYDPTRAK HNALLARYGC FLKNPGDFDH
RLFNISPREA MQMDPVQRML LMTTYEALEM AGYSPPTPAA PGDSEQAPPR IATYFGQTID
DWKSINDQQG IDTHYLPGVN RGFAPGRLSH FFQWAGGFYS IDTGCSSSAT ALCLARDALT
AGKYDAAVVG GGTLLTAPEW FAGLSQGGFL SPTGACKTYS DSADGYCRGE GVGVVILKRL
ADAVRSKDNV IAVIAGASRN CNAGAGSITY PGEKAQGALY RRVMRQAAVR PEQVDVVEMH
GTGTQAGDRV ETHAVQSVFA PSNGNQREKP LIVGALKANI GHSEAAAGII SLMKAILILQ
HDKIPAQPNQ PIKMNPYLEP LIGKQIQLAN GQSWTRNGAE PRYIFVNNFD AAGGNVSMLL
QDPPAFALPA PASGPGLRTH HVVVTSGRTA TAHEANRKRL HAYLSAHPDT NLADLAYTTT
ARRIHNVHRE AYVASSTSDL VRQLEKPLAD KVESAPPPAV VFTFTGQGAQ SLGMGGALYS
TSPTFRRLLD SLQSICEVQG LPTKFLNAIR GSGAEGATVT EVDMQVATVA LEIALARYWR
SLGIRPTVLI GHSLGEYAAL CVAGVLSASD ALALAFRRAT LIFTRCPPSE AAMLAVGLPM
RTVQYRIRDS AATTGCEVCC VNGPSSTVVG GPVAAIQALD EYLKSDGKVS TTRLRVQHAF
HTRQMDVLLD ELEASAAQVP FHAPTLPVAS TVLGRIVRPG EQGVFDANYL RRHTREPVAF
LDAVRACETE GLIPDRSFAV EIGPHPICIS LMATCLQSAK INAWPSLRRG GDDWQSVSST
LAAAHSAQLP VAWSEFHKDH LDTVRLISDL PTYAFDLKTF WHSYKTPAAA VSAASATPST
TGLSRLASTT LHAVEKLQRE EGKILGTFTV DLSDPKLAKA ICGHVVDESA ICPASIFIDM
AYTAAVFLEQ ENGAGAALNT YELSSLEMHS PLVLREDIEV LPQVWVEAVL DIKSNAVSVH
FKGQTSKGAV GYGSATMRLG QPDSAVRRDW SRIQSLVRAR VQTLNRSVRP REVHAMDTAL
FYKVFSEIVD YSAPYHAVQE AVIAADFHDA AVTLQLTPTA DLGTFTSSPF AVDALVHVAG
FLLNADVRRP KNEVHIANHI GSLRIVGDLS SPGPYHVYAT IREQDQKAGT SLCDVYTTDS
QDRLVAVCSD ICFKKLERDF FALLTGATRG RSTKPVAAAP AKSMAKRARQ LAPSPSPSSS
SGSNTPMSRS PTPSSVSDMV DLGTELLQAV AEQTGVSVAE MKSSPGTTFT EFGVDSQMAI
SILANFQRTT AVELPAAFFT NFPTPADAEA ELGGSALDDL EEDITKPTPS PEQTQARKQG
PAPSQHLLSL VAQALGLEAS DLTPSTTFDS VGMDSMLSIK ITAAFHAKTG IELPAAFFSA
NPTVGAAQEA LDDDAEEESA PAQTSTNPAK ETTIDSSRQH KLDAAVSRAS YIHLKALPKG
RRIYALESPF LEQPELFDLS IEEMATIFLR TIRRIQPHGP YLIGGWSAGS MYAYEVAHRL
TREGETIQAL IILDMRAPSL IPTSIVTTDF VDKLGTFEGI NRARDLPEDL SVKERAHLMA
TCRALSRYDA PAFPSDRQPK QVAVVWALLG LDNRPDAPIA SMGRPGLDIG KSMYEMNLDE
FERYFNSWFY GRRQQFGTNG WEDLLGDHIA VYTVNGDHFS MMCPPYASEV GDIVIETVTR
AVE
