TPCC_ASPFU
ID TPCC_ASPFU Reviewed; 1782 AA.
AC Q4WQZ5;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 103.
DE RecName: Full=Atrochrysone carboxylic acid synthase {ECO:0000305|PubMed:26242966};
DE Short=ACAS {ECO:0000305|PubMed:26242966};
DE EC=2.3.1.- {ECO:0000305|PubMed:26242966};
DE AltName: Full=Non-reducing polyketide synthase tpcC {ECO:0000303|PubMed:26242966};
DE AltName: Full=Trypacidin synthesis protein C {ECO:0000303|PubMed:26242966};
GN Name=tpcC {ECO:0000303|PubMed:26242966};
GN Synonyms=tynC {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14560;
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 FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22319557; DOI=10.1371/journal.pone.0029906;
RA Gauthier T., Wang X., Sifuentes Dos Santos J., Fysikopoulos A., Tadrist S.,
RA Canlet C., Artigot M.P., Loiseau N., Oswald I.P., Puel O.;
RT "Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic
RT to lung cells.";
RL PLoS ONE 7:E29906-E29906(2012).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26278536; DOI=10.1007/s00253-015-6898-1;
RA Mattern D.J., Schoeler H., Weber J., Novohradska S., Kraibooj K.,
RA Dahse H.M., Hillmann F., Valiante V., Figge M.T., Brakhage A.A.;
RT "Identification of the antiphagocytic trypacidin gene cluster in the human-
RT pathogenic fungus Aspergillus fumigatus.";
RL Appl. Microbiol. Biotechnol. 99:10151-10161(2015).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND 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 trypacidin, a mycotoxin with
CC antiprotozoal activity and that plays a role in the infection process
CC (PubMed:26278536, PubMed:26242966). The pathway begins with the
CC synthesis of atrochrysone thioester by the polyketide synthase (PKS)
CC tpcC (PubMed:26242966). The atrochrysone carboxyl ACP thioesterase tpcB
CC then breaks the thioester bond and releases the atrochrysone carboxylic
CC acid from tpcC (PubMed:26242966). The decarboxylase tpcK converts
CC atrochrysone carboxylic acid to atrochrysone which is further reduced
CC into emodin anthrone (PubMed:26242966). The next step is performed by
CC the emodin anthrone oxygenase tpcL that catalyzes the oxidation of
CC emodin anthrone to emodin (PubMed:26242966). Emodin O-methyltransferase
CC encoded by tpcA catalyzes methylation of the 8-hydroxy group of emodin
CC to form questin (PubMed:26242966). Ring cleavage of questin by questin
CC oxidase tpcI leads to desmethylsulochrin via several intermediates
CC including questin epoxide (By similarity). Another methylation step
CC catalyzed by tpcM leads to the formation of sulochrin which is further
CC converted to monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes
CC the conversion of monomethylsulfochrin to trypacidin (PubMed:26242966).
CC Trypacidin is toxic for human pulmonary and bronchial epithelial cells
CC by initiating the intracellular formation of nitric oxide (NO) and
CC hydrogen peroxide (H(2)O(2)), thus triggering host necrotic cell death
CC (PubMed:22319557). The trypacidin pathway is also able to produce
CC endocrocin via a distinct route from the endocrocin Enc pathway
CC (PubMed:26242966). {ECO:0000250|UniProtKB:Q0CCY3,
CC ECO:0000269|PubMed:22319557, ECO:0000269|PubMed:26242966,
CC ECO:0000269|PubMed:26278536}.
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:26242966};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC Evidence={ECO:0000305|PubMed:26242966};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26242966, ECO:0000269|PubMed:26278536}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
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: Impairs the production of trypacidin and pathway
CC intermediates including questin (PubMed:26278536, PubMed:26242966).
CC Leads to enhanced phagocytosis ratio by macrophages and amoebae
CC (PubMed:26278536). {ECO:0000269|PubMed:26242966,
CC ECO:0000269|PubMed:26278536}.
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; AAHF01000005; EAL89339.1; -; Genomic_DNA.
DR RefSeq; XP_751377.1; XM_746284.1.
DR AlphaFoldDB; Q4WQZ5; -.
DR SMR; Q4WQZ5; -.
DR STRING; 746128.CADAFUBP00006997; -.
DR EnsemblFungi; EAL89339; EAL89339; AFUA_4G14560.
DR GeneID; 3509595; -.
DR KEGG; afm:AFUA_4G14560; -.
DR VEuPathDB; FungiDB:Afu4g14560; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR InParanoid; Q4WQZ5; -.
DR OMA; AAYGHKM; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
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: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; IMP:AspGD.
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; 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; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
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; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 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; SSF52151; SSF52151; 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; 1.
PE 2: Evidence at transcript level;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..1782
FT /note="Atrochrysone carboxylic acid synthase"
FT /id="PRO_0000437050"
FT DOMAIN 1704..1781
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 41..270
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 410..844
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 946..1266
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1331..1648
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1652..1703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 580
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1741
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1782 AA; 194340 MW; 40ADDE88312785DE CRC64;
MRPVDFTPSS ESPTAEKGMK VVYFGNELPQ DGIQGICRRL HTYTKDRRYP LLARFIEEST
WAVHDEVRQL HAAQKALVSP FESVLHLAEQ PELCRGPLCG SIEGVLLCVI QLGTFIGYYE
DSPNEYTFDS ANTYLTGLGL GLLASTAVSL SPTLADLPLA GAEVVRVAFR LGVLVADVSQ
NLQPADATGE RDSWAYVIPN VAPKEAEEEL AVIHTRENTP EASRIFISAI SRTSVTISGP
PARLRRLFRM SDFFRDRTFV ALPVYGGLCH AKHIYNSQHA RSVVQGPSIA ALDTRFIARY
PILSTGSGEP FPTATTATEL FEHVMTEILT QAIEWENVIQ GVVERAKLLS VSEVQVQVFR
NSHPVHDLLS ALETSLREGV EVAIKDLGPW ITRTRDEERP PPRGTAQSKI AIVGMSCRMP
SGATDTEKFW DILEQGLDVH RKIPPDRFDV DSHYDPAGKR VNASHTPYGC FIDEPGLFDA
PFFNMSPREA QQTDPMQRLA IVTAYEALER AGYVANRTRS SNKHRMGTFY GQASDDYREV
NSAQEISTYF IPGGCRAFGP GRINYFFKLW GPSFSIDTAC SSSLATIQAA CTALWNGDTD
TVVAGGMNVL TNSDAFAGLS HGHFLTKTPN ACKTWDCEAD GYCRADGVAS IVMKRLEDAE
ADNDNILGVI LGAATNHSAE AISITHPHAG AQSCLSRQVL RSAGIDPMDV SYVEMHGTGT
QAGDAEEIKS VSDVFAPAVK RRSSQQPVFI GAVKANVGHG EAVAGVTALV KVLLMFQKEA
IPPHVGIKNS INPGFPKDLD QRNLRIPYEK KPWPRRPGRK RIAMVNNFSA AGGNSTLAIE
EGPLRPKPAG AIDPRSSHLV TVSAKSKISL KGNLERLLSF LDAHPDVALS DLAYTTTARR
HHHNHRVAVA TSDIADLKAQ LCKTLESDSV NTLQPISATG PPPIAFAFTG QGSSYKSWDL
QLFQHSPYFR SQILHLDTLA QGQGFPSFVP AIDGSYPRDH AHCPVITQLA LVCTEIALAK
YWVSLGVTPD VVVGHSLGEY AALHIAGVLS ASDAIFLVGQ RACLLQERCQ PSSHQMMAVR
ASLEQIEQFA GSLPYEIACV NGPREMVLSG TREEMAAVAR LLEAEGFKCI VLEVAFAFHS
AQMDPILDEF EALAASGVVF QAPNLPVISP LLSKVVFDEH TIDSVYMRRA TRETVHFLSA
MKMAHKISTI DDATVWVEIG PHPVCVNFVR SSLPSTSVTV PSFRRGEDNW VTLTSSLGIL
HCAGVPVDWN EFHQPFERAL RLLDLPTYSW NEKTYWIQYQ GNWALTKGNT FYDDEAPQTK
ALAGLASELR TSTVQQIIHE QYDGAAGSVV MQSDLMQPDF LAAAYGHKMN GRGVVTSSIH
ADIAFTLGEY LYKKLNPNQE PHMNIANLEV VKALVAQENT KSPQLIQVSA STDNIRSRQA
HLKWHNVING SIEEPFASAT VYYEEASDWL ASWRPATHLV QGRIHALEQL AEDGVANRFT
RRMAYGLFAS SLVDYADKYR GMQSVVLHEL EAFADVVLTT EKGGTWTVPP YFIDSVAHLA
GFIMNVSDAN DTNANFCVTP GWSSMRFAAP LLPGSKYRSY VKMIPTVEDN NIYLGDVYIL
QDETIVGMVG GIKFRRYPRI LLNRFFSAPD ADARKSTPAT SAPAPAPPAG SEALQPKAAP
ASTPAAPASA DAPTTNGVKA AAEPDANSTA AKAIALVATE AGLGLSDLKD SASFSSLGID
SLMSLVISEK FRETLGVTVT GSLFLEYPTV GDLKSWLLEY YS
