PKFA_EMENI
ID PKFA_EMENI Reviewed; 2193 AA.
AC Q5B8A0; A0A1U8QK04; C8VI76;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 128.
DE RecName: Full=Non-reducing polyketide synthase pkfA {ECO:0000303|PubMed:22510154};
DE Short=NR-PKS pfkA {ECO:0000303|PubMed:22510154};
DE EC=2.3.1.- {ECO:0000269|PubMed:22510154};
DE AltName: Full=Aspernidine A biosynthesis cluster protein pkfkA {ECO:0000303|PubMed:23706169};
GN Name=pkfA {ECO:0000303|PubMed:22510154}; ORFNames=ANIA_03230;
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).
RN [4]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, FUNCTION, AND PATHWAY.
RX PubMed=23706169; DOI=10.1021/ol401187b;
RA Yaegashi J., Praseuth M.B., Tyan S.W., Sanchez J.F., Entwistle R.,
RA Chiang Y.M., Oakley B.R., Wang C.C.;
RT "Molecular genetic characterization of the biosynthesis cluster of a
RT prenylated isoindolinone alkaloid aspernidine A in Aspergillus nidulans.";
RL Org. Lett. 15:2862-2865(2013).
RN [5]
RP INDUCTION.
RX PubMed=25701285; DOI=10.1534/genetics.115.174342;
RA Oiartzabal-Arano E., Garzia A., Gorostidi A., Ugalde U., Espeso E.A.,
RA Etxebeste O.;
RT "Beyond asexual development: modifications in the gene expression profile
RT caused by the absence of the Aspergillus nidulans transcription factor
RT FlbB.";
RL Genetics 199:1127-1142(2015).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of aspernidine A, a prenylated
CC isoindolinone (PubMed:23706169). The starting point of the biosynthesis
CC of aspernidin A is the production of orsellinaldehyde by the non-
CC reducing polyketide synthase pkfA, via condensation of one acetyl-CoA
CC starter unit with 3 malonyl-CoA units (PubMed:22510154). Hydroxylation,
CC methylation of one of the phenol groups, and prenylation, presumably
CC catalyzed by the prenyltransferase pkfE, would be needed to yield
CC aspernidine D (Probable). Subsequently, the cytochrome P450
CC monooxygenase pkfB is responsible for hydroxylation of aspernidine D to
CC yield aspernidine E (PubMed:23706169). The dehydrogenase pkfF may be
CC responsible for further oxidation of aspernidine E to form a dialdehyde
CC intermediate which is further transformed in a series of steps, some of
CC which are enzyme-mediated, to generate aspernidine A (Probable). The
CC possibility that additional enzymes outside of the cluster are involved
CC in aspernidine A biosynthesis cannot be excluded (Probable).
CC {ECO:0000269|PubMed:22510154, ECO:0000269|PubMed:23706169,
CC ECO:0000305|PubMed:23706169}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + AH2 + 3 H(+) + 3 malonyl-CoA = A + 3 CO2 + 4 CoA
CC + H2O + orsellinaldehyde; Xref=Rhea:RHEA:64520, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:155863;
CC Evidence={ECO:0000269|PubMed:22510154};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64521;
CC Evidence={ECO:0000269|PubMed:22510154};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22510154, ECO:0000269|PubMed:23706169}.
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 domain, a
CC acyl carrier protein (ACP) domain, a methyltransferase domain and a
CC reductive NADPH-binding domain that is required for NADPH-dependent
CC product release. {ECO:0000305|PubMed:22510154}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of Aspernidine A.
CC {ECO:0000269|PubMed:23706169}.
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; AACD01000054; EAA63131.1; -; Genomic_DNA.
DR EMBL; BN001306; CBF83139.1; -; Genomic_DNA.
DR RefSeq; XP_660834.1; XM_655742.1.
DR AlphaFoldDB; Q5B8A0; -.
DR SMR; Q5B8A0; -.
DR STRING; 162425.CADANIAP00009832; -.
DR EnsemblFungi; CBF83139; CBF83139; ANIA_03230.
DR EnsemblFungi; EAA63131; EAA63131; AN3230.2.
DR GeneID; 2874277; -.
DR KEGG; ani:AN3230.2; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_2_1; -.
DR InParanoid; Q5B8A0; -.
DR OMA; VEITAYC; -.
DR OrthoDB; 13314at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
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: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; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..2193
FT /note="Non-reducing polyketide synthase pkfA"
FT /id="PRO_0000446353"
FT DOMAIN 1627..1701
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:22510154"
FT REGION 55..202
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 363..774
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 873..1171
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 1289..1577
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT REGION 1701..1737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1815..2136
FT /note="NADPH-binding (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:22510154"
FT ACT_SITE 127
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 249
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 521
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1661
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2193 AA; 241709 MW; E701A2911ED08CF7 CRC64;
MQGSSHTLLA FGPQSLSFDK RALIKLRGDI SSGRYGQWIQ DTIAGLPGFW TALSEALPEL
RELLPPQERL QDLDRLLNHS IDDIEEGLSI SNMILTPLVV LTHLTEYERY LATNQHTSDR
TTATGFCTGL LSTFAIASSR NDQELAKYGA VALRLAMLVG ALVDAEERRQ ELQGNGRSVS
YSIAWMSEEQ QQRLQEILGQ RHPETYLSVR YDRARATLTS SGRAAADLAQ ELREIGLTVA
QVRLQGRFHD PSESRKAYTD ALADLCNRTP ELQFAPTPAM SLAYPKIDNA SLHEVAVRSM
LVQHCDWYDT FKAAYPEVSS PARVVCFGSE RCIPPTLAKR TVKIESQHQA SDAFASLDQE
NMIAVVGMSI KTAGADDVDE FAQMLRTGTS QHQAIMEDDI NFNTPWRTDK GSRTWYSNLI
RDRSQFDHSF FKMSPREAAA MDPQHRLFLQ AAYQAVEQSG YFLEPGHNET KLPEDSVGVF
HVSCYDPNAY TATGNLRAFL AGRVSHHFGW TGPALTLDTA CSSSAVAIHL ACRSILSGEC
SAALAGGVAV MSSPFWFQNL GAASFLSPTG QCKPFDEKGD GYCRSEGIGC VMLKKMSAAV
ANNDQILGCI GASAVHQNQN CTAVVVPNKP SLAPLFKQVI SKSGLTPADI SLVEAHGTGT
AVGDPAEYAS IADALNVASR PSPLILGSVK GHIGHTEAAA GVVSLIKVLM MMNEGFIPPQ
ASHTRLSPRI TAATDKLRIS TSLRPWETDQ KAALVNSYGA SGSNTSMVIL QLPKRHTFPH
QGVTKDGLAQ PFWISGTNEV EITAYCARLA EYIRTRPTVR LDDLSFNLSR QCNRTLARQL
VFSCRSMSEL QAMLSRGASA EGSSKVVPTE RPVILCFGGQ VSTFVGLNRL VYENVGLLRR
YLDECDMAMT NMGLESIYPE IFSTSPVQDT VKLQCMLFAM QYSCARCWLD CGVSTRIAAV
VGHSFGELTA LSISGVLSVQ DTIKLVAGRA RLIRDQWGSD RGAMMAVEGD ESTIQQLLEE
ASQQTPSDHP ATIACYNGPR SFTLGGSTAA IEGVKETLLS KYPYIRHKRL NVTNAFHCSL
VGNIVEPLNQ LGEELTFNSP VIHIEHSSST PSTGARPSST FVADHLRKPV YFYHAIERLA
RAYPDSIWLE AGSNSTITTM AGRALRPTSD IVGQSHHHFQ ALNITHGGRG SDSLTETTLS
LWKEGLRVSF WQHHPVQKDQ YEHLILPPRQ FARTRHGLDI IAPKTDQGAA QQTGVPKPDG
LWTFVGYEDN NRSRPRFLIN SNSEKYLAMV EGHVMARTAA ICPAGLEVDM AIEALFSLQP
EWKERRLQPM LRDMVNSAPV CLDPIRKFWL QLSAADESCM LWDWNITSTR EGSSSSLLHV
KGSLQIRSPE DPLYRNDFAR LERLVPYRQC TDILALAGAQ PDDLDDEIHV LQGRNVYQGF
SDVISYTPLY RSLRRLVGRG NESAGCVIRK RSHETWLDVP LSECFMQTGG IWVSCMTDRS
PDDVFIATGC ELWMRSPSLA DVKEKGEDGT EKWHVLARHL RVSDKVYLTD VFVFDSRTGA
LTEVIMGTKF SRLPKTVMRK ILSDFHPGNP SVHEKDIVTA APKQPIIQAQ EIVLAEAPRK
HKSVQKRDIT GQVCQLLSSV SGIEPAKINQ NAELSDLGVD SLMAMELARE IEGVFKFSPD
HNDLLEATTV EKLTNYISSS IPGSSAASEN IDNHGSPNDT DSSGESDPAT PTVACSSTDD
FREPFIITSS RDEAEVLSLA ESDDTFLKSQ RPIVEMAKQN TDREEIAEQY VARYTAGFIP
PVSSRSSARE HSGNVVIITG ATGSLGSHLV ASFARDPSVR TVICLNRRSK TPGTLRQSQA
LSTRKLQLTE AESSKLRMLD GNTSEPHLGL AADEYTWLAR NATHIVHNAW PMSLARPIHT
FVPQFQALRN LLDLAREMAC NCSPNGMRVG FQFVSSISVV GSAAQQRVLE QRVDLRSSLP
IGYPEAKWVC ERMLDETLHR YPDHFRPMVV RPGQITGSSH TGCWPHTEHM PLLIKTAQTL
QAWPDLDGPL HWVPVDTVAQ TMVDLLLPGI ESDSNQTGTT LNKSEPDAYP VYHIDNPVGQ
PWKEMTPIIT SALNIPSDRV IPYQEFLNLL RSSPLDRDRE IPAAKIMDFF TRDFEHMACG
GLVLDTTLSQ EHSATLAAQG PVTEEENMKI LTL
