PKHA_EMENI
ID PKHA_EMENI Reviewed; 2221 AA.
AC Q5BBP8; C8VLG0;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Non-reducing polyketide synthase pkhA {ECO:0000303|PubMed:22510154};
DE Short=NR-PKS pkhA {ECO:0000303|PubMed:22510154};
DE EC=2.3.1.- {ECO:0000269|PubMed:22510154};
DE AltName: Full=Pkh biosynthesis cluster protein B {ECO:0000303|PubMed:22510154};
GN Name=pkhA {ECO:0000303|PubMed:22510154}; ORFNames=ANIA_02032;
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 DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22510154; DOI=10.1021/ja3016395;
RA Ahuja M., Chiang Y.M., Chang S.L., Praseuth M.B., Entwistle R.,
RA Sanchez J.F., Lo H.C., Yeh H.H., Oakley B.R., Wang C.C.;
RT "Illuminating the diversity of aromatic polyketide synthases in Aspergillus
RT nidulans.";
RL J. Am. Chem. Soc. 134:8212-8221(2012).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the pkh gene
CC cluster that mediates the biosynthesis of 2,4-dihydroxy-6-[(3E,5E,7E)-
CC 2-oxonona-3,5,7-trienyl]benzaldehyde (PubMed:22510154). The highly
CC reducing polyketide synthase pkhB first produces the (2E,4E,6E)-octa-
CC 2,4,6-trienyl strater unit for the non-reducing polyketide synthase
CC pkhA (PubMed:22510154). This octatrienoyl starter is then loaded onto
CC the SAT domain of the NR-PKS pkhA to be condensed with 4 malonyl-CoA
CC units to yield 2,4-dihydroxy-6-[(3E,5E,7E)-2-oxonona-3,5,7-
CC trienyl]benzaldehyde (PubMed:22510154). {ECO:0000269|PubMed:22510154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,4E,6E)-octa-2,4,6-trienyl-[ACP] + AH2 + 3 H(+) + 4
CC malonyl-CoA = 2,4-dihydroxy-6-[(3E,5E,7E)-2-oxonona-3,5,7-
CC trienyl]benzaldehyde + A + 4 CO2 + 4 CoA + H2O + holo-[ACP];
CC Xref=Rhea:RHEA:64524, Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16617,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17499, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:64479, ChEBI:CHEBI:155862,
CC ChEBI:CHEBI:155872; Evidence={ECO:0000269|PubMed:22510154};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64525;
CC Evidence={ECO:0000269|PubMed:22510154};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:A0A0K0MCJ4};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22510154}.
CC -!- DOMAIN: Multidomain protein; including an N-terminal starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template (PT)
CC domain that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone, an acyl carrier protein (ACP) domain, and
CC a reductive NADPH-binding domain that is required for NADPH-dependent
CC product release. {ECO:0000305|PubMed:22510154}.
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DR EMBL; BN001307; CBF86046.1; -; Genomic_DNA.
DR RefSeq; XP_659636.1; XM_654544.1.
DR AlphaFoldDB; Q5BBP8; -.
DR SMR; Q5BBP8; -.
DR STRING; 162425.CADANIAP00008700; -.
DR EnsemblFungi; CBF86046; CBF86046; ANIA_02032.
DR EnsemblFungi; EAA64864; EAA64864; AN2032.2.
DR GeneID; 2875205; -.
DR KEGG; ani:AN2032.2; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_2_1; -.
DR InParanoid; Q5BBP8; -.
DR OMA; FERMACG; -.
DR OrthoDB; 13314at2759; -.
DR Proteomes; UP000000560; Chromosome VII.
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: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; IPR013120; Far_NAD-bd.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
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; 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; PF07993; NAD_binding_4; 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 SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
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.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2221
FT /note="Non-reducing polyketide synthase pkhA"
FT /id="PRO_0000450876"
FT DOMAIN 1666..1743
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 104..237
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 406..830
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 905..1197
FT /note="Malonyl-CoA:ACP transacylase (MAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 1298..1612
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000305|PubMed:22510154"
FT REGION 1632..1665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1745..1796
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1850..2093
FT /note="NADPH-binding domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 1880..1899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1746..1760
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1761..1775
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1776..1796
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 268
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 576
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1703
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2221 AA; 241564 MW; 22F86FC84EFAF3D2 CRC64;
MKPSSNICQA TSFIFGGHIG PQTKNSLEKE IREVANGPNG GWILDTLAGM PRYWEAVTEK
IPEVASTMQG VQLLSDLESW FRIGSDSVDS LAPDAELPDL WLGILMVIIQ LDQYWRYLES
RFADRAVDDL QGELIKEEKV EAVGFCAGMI AAVAIASSHT RQEFKKYGAV ALRIAALMAI
LVGATEEWTK AMGKGRSVSF ATAWRTRKQG DDMARIISKL SPDAYISVIL DDSRATVTVS
ERLAPKLVRQ LRAAGVTAIQ LAFKGQLHSP TAERKRLTEA VVELCQSMPE LRYPVAARLA
LPINQVSGQE TDLVGMVLRS MLVNQLNWTS TTSMLTLNKE ELSRVEFGLD RPLPPPVVRA
FGAMLDYKEV DVPKHRQYDK GKEPVHDTES VQVAEPPLQE ADENVIAVVG MSIKVAGAND
LEEFQQMLKT GHSQHQLVTN DHITPNMMFR NKVPNRKWYG NFVRDPDAFD HKFFKKSPRE
SMAIDPQGRL SLEAAYQALE QSGYFNELTM TSAAEQERKK HVGVYVGVCS YEYDSNVHCH
PPSAFTTTGE LRSFIPGRIS HYFGWTGPSL TFDTACSSST VALHNACRDL LSGEVPAALC
GGVNILTSLQ WTQNLAAGSF ISPTGQCKPF DSGADGYCRG DGIAYVFLKK LSNAVADGNT
VLGTICSTGV NQNLNTTPLF VPNVPSLSTL FNEVIRKARI ARRDISLVEC HGTGTPVGDP
AEWQSIRNAV AGPRRDTVLP IGSVKGHVGH TEGASGLVSL IKVLMMMRGN FIPPQASFNT
MSPGIHAQPS DNMEVVTALR SWPGAQKVAL INNYGACGSN SSAIVAHSAH KPVKGPLSGG
QRLPFWISGL DARSIAAYST ALASYLHSQD QAASLADAKL ALAAKATKDT APSVGIVPVK
PERPVILCFG GQVSTFIGLD RAVYEGASVF RHHLDTCNAA ITSHSLESIY PDIFSSEPYQ
DTIKLQTALF AMQYASAKTW MDCGIAEKVV SVVGHSFGEI TALCVSGVLS LEDSVKLIAG
RAKLVQTAWG ADSGSMMAIE ADGAVVQDLL QESNARSDGT AGIACYNGPR SFTVAGSTKA
IDAFAATLPG KEVKSKRLNV TNAFHSALVE SIVDRLGEVG KEVTFHDAVI PIERATEHSG
DATLDWTFVG SHMRRPVFFN HAVQRLAEKY PDAIFLEAGS NSTITVMASR ALANPKSTHH
FQSISITNTN KGIARLTDAT VDLWKQGLRV SFWAHHRFQK DEYAQLLLPP YQFEKTRHWL
ELKSPIEQAM NIAKVQDGIA AQKGHVNNKS LEIWTFLGFQ KQKKKTKLAR FRINTSSDKY
QRLFATHVIA KTAPIAPATL EIDMAIETLF SLNPEWRQSG FSPVIRDMLS HSPMCADSTR
EYFLDLVPLN PTETEWQWTI QSTGTSSAND KHAEGRIAMY SSSDPAALQE FGRWERIVTY
AQCQAVLALG SQDEGVEALQ GRNVYRAFEE VVDFGSVYRG VKYIVGQEKG ESAGIVHKQH
SGDTWLDVPK ADCYGQIAGM YVNLLTDIPS SDMFVATGLE LVMRSPKAQT VTDGRENGPN
VWHVLARHAR QGEKAYVTDV FVFDASTGAL AEVILGLQYV RVPKATMSKI LARMTTDKSF
VRSTATASLL LPDRPQPHDG PITATVPRPA PPKATKTNVA KTEPVSSARN IAKEVCNVVA
NVSGIEASEL SLDSEMADLG IDSLMAMEVA REMENTFHCT LDSTETMVAT NIRDFAACVS
NALARSGGQD GASTSTESDA MLSDSEDEDT DSGISTPDDA SEITSKSHDP VSEPLTSTIL
NVDHGDVAAR NAEALRLVEA YTAGWDSRAV KDANNRIITT GSGDGAVVIV TGASGSLGSH
LVQALAERPD VSGVVCINRP VKDTPPDSRQ EEALSSRSIK LSPAAREKLQ VYGTDTSKAQ
LGLSKKEYNW LAQHGTHIIH NAWPMSATRP LKAFEPQLQV MRNMLDLARD MALGDEPRRI
GFQFVSSIGV TGLSNESPVL EQPVAFAATI PGGYNEAKWT CERMLTDTLR RHPQLFQAMV
ARPGQISGST ASGFWNPVEH FPFVVKSAHA LKVFPDLQGV LHWLPVDKAA SIMVDLLSIS
GSKGSGEVYP VYHVDNPVGQ LWKEMVTVLA ASLDIPPHGI VPFREWIQRV RQSSLPPAQN
PASMGLGFLE SHFERMACGG IVLDTQHSRE HSETMAAQGP VSAEVVRSYV SSWKAMGLLR
H
