ENCA_ASPFU
ID ENCA_ASPFU Reviewed; 1775 AA.
AC Q4W944;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Atrochrysone carboxylic acid synthase {ECO:0000305|PubMed:22492455};
DE Short=ACAS {ECO:0000305|PubMed:22492455};
DE EC=2.3.1.- {ECO:0000305|PubMed:22492455};
DE AltName: Full=Endocrocin synthesis protein A {ECO:0000303|PubMed:22492455};
DE AltName: Full=Non-reducing polyketide synthase encA {ECO:0000303|PubMed:22492455};
GN Name=encA {ECO:0000303|PubMed:22492455}; ORFNames=AFUA_4G00210;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=20379952; DOI=10.1055/s-0030-1249779;
RA Gautam R., Karkhile K.V., Bhutani K.K., Jachak S.M.;
RT "Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free
RT radical scavenging effects of Rumex nepalensis.";
RL Planta Med. 76:1564-1569(2010).
RN [3]
RP FUNCTION.
RX PubMed=22492455; DOI=10.1128/aem.07710-11;
RA Lim F.Y., Hou Y., Chen Y., Oh J.H., Lee I., Bugni T.S., Keller N.P.;
RT "Genome-based cluster deletion reveals an endocrocin biosynthetic pathway
RT in Aspergillus fumigatus.";
RL Appl. Environ. Microbiol. 78:4117-4125(2012).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23592999; DOI=10.1371/journal.ppat.1003289;
RA Berthier E., Lim F.Y., Deng Q., Guo C.J., Kontoyiannis D.P., Wang C.C.,
RA Rindy J., Beebe D.J., Huttenlocher A., Keller N.P.;
RT "Low-volume toolbox for the discovery of immunosuppressive fungal secondary
RT metabolites.";
RL PLoS Pathog. 9:E1003289-E1003289(2013).
RN [5]
RP INDUCTION.
RX PubMed=26242966; DOI=10.1111/1462-2920.13007;
RA Throckmorton K., Lim F.Y., Kontoyiannis D.P., Zheng W., Keller N.P.;
RT "Redundant synthesis of a conidial polyketide by two distinct secondary
RT metabolite clusters in Aspergillus fumigatus.";
RL Environ. Microbiol. 18:246-259(2016).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of endocrocin, a simple anthraquinone
CC interesting for many biotechnological applications (PubMed:22492455,
CC PubMed:23592999). The pathway begins with the synthesis of atrochrysone
CC thioester by the polyketide synthase (PKS) encA (PubMed:22492455). The
CC atrochrysone carboxyl ACP thioesterase encB then breaks the thioester
CC bond and releases the atrochrysone carboxylic acid from encA
CC (PubMed:22492455). The atrochrysone carboxylic acid is then converted
CC to endocrocin anthrone which is further oxidized into endocrocin by the
CC anthrone oxygenase encC (PubMed:22492455). The exact function of encD
CC has not been identified yet, but it negatively regulates endocrocin
CC production, likely through the modification of endocrocin itself
CC (PubMed:22492455). {ECO:0000269|PubMed:22492455,
CC ECO:0000269|PubMed:23592999}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8 H(+) + holo-[ACP] + 8 malonyl-CoA = atrochrysone carboxyl-
CC [ACP] + 8 CO2 + 8 CoA + 2 H2O; Xref=Rhea:RHEA:64232, Rhea:RHEA-
CC COMP:9685, Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:64479, ChEBI:CHEBI:149712;
CC Evidence={ECO:0000305|PubMed:22492455};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC Evidence={ECO:0000305|PubMed:22492455};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22492455}.
CC -!- TISSUE SPECIFICITY: Endocrocin is specifically produced in conidia.
CC {ECO:0000305|PubMed:23592999}.
CC -!- INDUCTION: Expression is positively regulated by the transcription
CC factors brlA and laeA (PubMed:26242966). {ECO:0000269|PubMed:26242966}.
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: Abolishes the production of endocrocin
CC (PubMed:22492455, PubMed:23592999). Leads to attenuated virulence in a
CC toll-deficient Drosophila invasive aspergillosis model
CC (PubMed:23592999). {ECO:0000269|PubMed:22492455,
CC ECO:0000269|PubMed:23592999}.
CC -!- BIOTECHNOLOGY: Endocrocin and related anthraquinones compounds have
CC interesting activities for medicinal uses, including anti-inflammatory
CC activity (PubMed:20379952). {ECO:0000269|PubMed:20379952}.
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DR EMBL; AAHF01000017; EAL84397.1; -; Genomic_DNA.
DR RefSeq; XP_746435.1; XM_741342.1.
DR AlphaFoldDB; Q4W944; -.
DR SMR; Q4W944; -.
DR STRING; 746128.CADAFUBP00009780; -.
DR PRIDE; Q4W944; -.
DR EnsemblFungi; EAL84397; EAL84397; AFUA_4G00210.
DR GeneID; 3503726; -.
DR KEGG; afm:AFUA_4G00210; -.
DR VEuPathDB; FungiDB:Afu4g00210; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_0_1; -.
DR InParanoid; Q4W944; -.
DR OMA; IALCRLW; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:1900602; P:endocrocin biosynthetic process; IMP:AspGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
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; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
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; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..1775
FT /note="Atrochrysone carboxylic acid synthase"
FT /id="PRO_0000437047"
FT DOMAIN 1698..1775
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 29..258
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 394..824
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 921..1241
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1305..1626
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1672..1694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 564
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1735
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1775 AA; 194076 MW; 26F725DCAA4E1B11 CRC64;
MQGPSQLALF YFANGLPPDD IQDLFQRLRS QSKTESGWTL RAFVVQATNA LREEIRQLPH
HLRNPLTPLD NALDLAVVPD WRRGPLAGAL EGVLLCLIEI GSLIAYYERT PDPFKFSART
ACFTGIGTGL LAAAAAAASP TLADLPRLGA AAVRIALRMG VLVAETSQSV EAREPDAPAD
NWAAVVMDLD EDTVREELNL FNASTNNLGP SRLFISAGGT DNVTISGPPS KLRQVFRVSE
KLRSARYAQL PVYGGLCHAP HLYNCHHWTW IMEPINGAAF NQNMVDTAPL FSAGDDVPFE
ASTPRQLFES VVCDLLMGMI RWNRAVDGVV ELLGQTLPSE CQVYAFRPCA VVTGMVASGQ
VKLPHCQFQT HDLLGWTCHD DTDNGPTCRE DSSIAIVGMA CRFPGGANDL NQFWDLLEQG
ADVHRRVPAD RYDVESHTDT SGKSRNTSLT PFGCFIDQPG LFDAGFFDMS PREAMQTDPM
HRLALMTAYE ALEQAGFVPN RTESTHLKRI GTFYGQSCDD YREANAGQEV DTYYIPGGCR
AFAPGRINYF FKFSGPSFDC DTACSSSLAT IQMACTSLQH GDTNMAVAGG LNILTNSDGF
AGLSRGHFLS KTGGCKTFDC NADGYCRADG IGSIVLKRLD DAQRDNDHIF GIILAAATNH
SARAISITHP HAPSQAELYR DILTRAGVSP LDVDFIEMHG TGTQAGDSTE MESITSVFSP
GVPKRSRPLY IGSVKANVGH GEAAAGVMSL IKVLLVLQRQ AIPKHVGIKT ALNPRFPNLD
RLNVRIPHDQ VPWPRSPTRK RYALVNNFSA AGGNTSLLIE EPPVRPEPKA DPRAAFTVAV
SAKSKASLKN NLRSFLAYLE SQPSISLAHL SYTTTARRMH HNHRIAVHGS TLSSIMQELE
PYLPAVDTHR PVPNTPPSIA FVFSGQGSFY TGIARQLYEH HPGFRLQITR LHNICLSHGF
PSFRRAITGD LSNDGSEAEP IITHLTIVCV SIALCRLWET LGVKPCVVAG ASLGEFAALY
AAGVLSASDA IYLVGRRAQL LQELCTPNTH AMLAVRATVE QIRNVLAGQP YEVACINGSS
DITLSCSVAD IINLQLAIEQ HGYKCTRLDV PFAFHSAQMD PLLGPFEHIA RGVTFKAPNI
PVMSPSLGDC VFDGKTINAS YMCNVTRNPV KFVDALETAR GMDLVDAKTV WVEIGPHASY
SRFVGSAMPP GTATIASLNR NEDNWSTFAR SMAQLHNLGV DLNWHEWHAP FESELRLLTD
LPAYQWNMKN YWIQYNGDWM LRKDGKSSAA AASHPHQAIP PALRTSLVHR LVCESVQETR
VEVIVESDIL HPDFFEAMNG HRMNGCAVAT TAIHADIAFT LAKYLYSSIM PNSTDAPAIN
VKNMQVQHGL VARKDRSRPQ LIRIRGIADV TRGLVSLSWH LVDEQGRRVE ESFATAVAEF
GNHEAWLEEW SPMTHLVVSR IDVLQRLADD GTANRLSRDM VYMLFNNLVD YAEKYRGMQM
VVLHGLEAMA NVTLAAPEQS GGKWTVAPHY IDSVVHLAGF ILNGGNGLDP RRNFYVTPGW
KSMRFARPLV PGVRYQSYVK MMPIREQSGF YAGDVYILHE GQIVGLVGGI TFRTFPRSLI
NTFFSPPDTM THGGSQAGSV HQPACSERTL PVGPARQDSA ARETLCQGHG LSRTVMDSSD
SSPATTLTPP TLPSVAASTE SPIVHRAMAL IAAETAIELT ELSDETAFSS IGVDSLLSLV
LAEKFTAEFH LDFRSSLFLD CPTIGDLKAW LIDYC
