AFOE_EMENI
ID AFOE_EMENI Reviewed; 2793 AA.
AC Q5BEJ6; C8VTX9;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Iterative polyketide synthase afoE {ECO:0000303|PubMed:19199437};
DE EC=2.3.1.- {ECO:0000269|PubMed:22510154};
DE AltName: Full=Asperfuranone biosynthesis protein B {ECO:0000303|PubMed:19199437};
GN Name=afoE {ECO:0000303|PubMed:19199437}; ORFNames=AN1034;
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 FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=19199437; DOI=10.1021/ja8088185;
RA Chiang Y.M., Szewczyk E., Davidson A.D., Keller N., Oakley B.R., Wang C.C.;
RT "A gene cluster containing two fungal polyketide synthases encodes the
RT biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus
RT nidulans.";
RL J. Am. Chem. Soc. 131:2965-2970(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=20148857; DOI=10.1111/j.1742-7843.2010.00545.x;
RA Wang C.C., Chiang Y.M., Praseuth M.B., Kuo P.L., Liang H.L., Hsu Y.L.;
RT "Asperfuranone from Aspergillus nidulans inhibits proliferation of human
RT non-small cell lung cancer A549 cells via blocking cell cycle progression
RT and inducing apoptosis.";
RL Basic Clin. Pharmacol. Toxicol. 107:583-589(2010).
RN [5]
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: Iterative polyketide synthase; part of the gene cluster that
CC mediates the biosynthesis of asperfuranone, a probable antitumor agent
CC (PubMed:19199437). The polyketide synthase afoG is responsible for
CC producing the 3,5-dimethyloctadienone moiety from acetyl-CoA, three
CC malonyl-CoA, and two S-adenosyl methionines (SAM) (PubMed:19199437).
CC The 3,5-dimethyloctadienone moiety is then loaded onto the SAT domain
CC of afoE and extended with four malonyl-CoA and one SAM, which leads to
CC the formation of 2,4-dihydroxy-6-(5,7-dimethyl-2-oxo-trans-3-trans-5-
CC nonadienyl)-3-methylbenzaldehyde (compound 2) after reductive release
CC and aldol condensation (PubMed:19199437, PubMed:22510154). AfoD is the
CC next enzyme in the biosynthesis sequence and hydroxylates the side
CC chain at the benzylic position of compound 2 (PubMed:19199437). After
CC benzylic hydroxylation, a furan ring is formed after five-member ring
CC hemiacetal formation and water elimination (PubMed:19199437). AfoF and
CC afoC are proposed to oxidize the R-diketone proton and to reduce the
CC unconjugated carbonyl group, respectively, to generate asperfuranone
CC (PubMed:19199437). Since no intermediates could be isolated from afoF
CC and afoC deletants, the sequence of these two enzymes is not fully
CC understood (PubMed:19199437). Moreover, since afoC deletant still
CC produces a small amount of asperfuranone, other endogenous
CC oxidoreductases might catalyze the same reaction with much less
CC efficiency (PubMed:19199437). {ECO:0000269|PubMed:19199437,
CC ECO:0000269|PubMed:22510154}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5E,7S)-5,7-dimethyl-2-oxonona-3,5-dienyl-[ACP] + AH2 + 3
CC H(+) + 4 malonyl-CoA + S-adenosyl-L-methionine = 6-[(3E,5E,7S)-5,7-
CC dimethyl-2-oxonona-3,5-dienyl]-2,4-dihydroxy-3-methylbenzaldehyde + A
CC + 4 CO2 + 4 CoA + H2O + holo-[ACP] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:64512, Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:16614,
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:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:155861, ChEBI:CHEBI:155871;
CC Evidence={ECO:0000269|PubMed:22510154};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64513;
CC Evidence={ECO:0000269|PubMed:22510154};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:19199437, ECO:0000269|PubMed:22510154}.
CC -!- INDUCTION: Expression is regulated by the asperfuranone cluster
CC transcription factor afoA (PubMed:19199437).
CC {ECO:0000269|PubMed:19199437}.
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:19199437,
CC ECO:0000305|PubMed:22510154}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC asperfuranone (PubMed:19199437). {ECO:0000269|PubMed:19199437}.
CC -!- BIOTECHNOLOGY: Asperfuranone provides anti-proliferative activity in
CC human non-small cell lung cancer cells (PubMed:20148857).
CC {ECO:0000269|PubMed:20148857}.
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DR EMBL; BN001308; CBF88295.1; -; Genomic_DNA.
DR EMBL; AACD01000015; EAA65602.1; -; Genomic_DNA.
DR RefSeq; XP_658638.1; XM_653546.1.
DR SMR; Q5BEJ6; -.
DR STRING; 162425.CADANIAP00001613; -.
DR PRIDE; Q5BEJ6; -.
DR EnsemblFungi; CBF88295; CBF88295; ANIA_01034.
DR EnsemblFungi; EAA65602; EAA65602; AN1034.2.
DR GeneID; 2876807; -.
DR KEGG; ani:AN1034.2; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_2_1; -.
DR InParanoid; Q5BEJ6; -.
DR OMA; WHVYARH; -.
DR OrthoDB; 13314at2759; -.
DR Proteomes; UP000000560; Chromosome VIII.
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 Gene3D; 3.40.50.150; -; 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; IPR041068; HTH_51.
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; IPR013217; Methyltransf_12.
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; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 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; SSF53335; SSF53335; 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; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2793
FT /note="Iterative polyketide synthase afoE"
FT /id="PRO_0000436373"
FT DOMAIN 1776..1850
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..401
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT REGION 433..810
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 977..1265
FT /note="Malonyl-CoA:ACP transacylase (MAT)"
FT /evidence="ECO:0000255"
FT REGION 1411..1696
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1734..1776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1853..1903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2115..2294
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000255"
FT REGION 2360..2379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2387..2630
FT /note="NADPH-binding domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1876..1895
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 279
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 611
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1810
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2793 AA; 303662 MW; 38F4F3E02DBBAEC3 CRC64;
MTRASASGSG HEASTVFLFG PHVGTFTKAS MDKLVRPLSQ SPQRDWILRT IADLPTYWDA
LAAKMPDIAR DIDGPTSLSE LDRWLRHSLD TAGLSVSDDE SLPSILVGPL VVLIQLTQYW
RHLEMIRDGS APAVDLQAEL VQQTQSGSRP TVILGFCAGL LAALSVASAR NQAGFEEYGA
VAVRLAMLIG ALIDAQEVWD KASGKGSSAS YAVAWRGQKQ EDEMNRIIGD LSNDAYVAVR
YDQARATVTA SETIAPLLMK RLRAAGVTVA EVGIKGQIHS PNADRKQHTN ALVELCASLP
GLQYAEVSKL ALQTYDNQGS GIPVSGSGNM TEMVVRSILV QQCRWFDTFS AVADALPDPY
VVTFGLERCV PPTLMRTLGG RQVFYEDLPK DPEKPSFWLT PQSSPPPQPQ LQPVLQLQQQ
QTTRVEPVMP VSPQSEPIAI VGMSVKTAGA DDLDEFVAML KTGQSQHIPI TRDRLMHDML
FRENADADPK RKFYGCFFRD GDAFDHKFFK RSPRESAAMD PQSRIVLQAA YQAVEQSGYF
VEDHNGYTPD GRDKMHVGVY LGSCGVDYEH NISCYDPNAF TATGALKSFI TGRVSHHFGW
TGPCMTFDTA CSSSAVAIHT ACRNLLSGEC TAALAGGSNT VTNMNWFQNL AAGSFVSPTG
QCKPFDDDAD GYCRAEGAAF VYLKRLSDAL RDGNQVIATI AASAVYQNEN CTPLFVPNSP
SLSHLFKDVM RQAKVTANDV SLVEAHGTGT PVGDPAEYES ILAALGGPSR KKKLPIGSVK
GHIGHTEGAS GAIALVKIIM MMREGFIPPQ ASFKTMNKKI PVKADDNIEV VTRLRAWEEE
RKTALLNNYG ACGSNASMIV TQPDLRGPHS RSHAVAGARY PFWIPGLDTR AITAYCAKLG
PWLRSRAEEP TLADISFNLS RQSNRGLPQG FIFNARSLAE LHEKIEQAVA AAPSSKDAAA
SVGIAPVKAE RPVILCFGGQ ISRFVGLDRG LFDAVALFRK HLDAVDTVVK AQGLVSIYAA
PDIFSREPIE DTVKLQTMLF AMQYACAQTW IDCGLNGKVQ ALVGHSFGEI TALCVAGTLS
LDETVRLVAA RAKLVRDSWG ADRGAMMALE GDEGLVHQLL SEANGASGSD GSASIACYNG
PRSFTIAGST SAVDQVQQTI SRPEFGSIKG KRLNVTNAFH SSLVDKISDG LDSIGKTLTF
NSPLIPVERA TEVASARATD ASFVSQHMRQ PVFFNHAVQR LAKRHPQAIF LEAGSSSTIT
VMAGRAIAQG QASSESHYFQ AVSITNETAL DSLADTTTAL WKQGLRVTFW AHDAVQTAEY
AHLLLPPYQF DTSSRHWLPM KSPVEKVKEA ALALIAANGG SLAGAGLQGQ QAGTPQDPRT
LPVWEFVGYQ DDETRQARFR VNTSADKYNR YVLSHVIAQT APICPGTLEC DIVIEALFSL
EPGWRQDGVQ PVVREMINHS PICKDPSRVV YLDLTATNKR RTNWTVRIFS LDDDATKKTP
EIHAEATVEM RSSSDQAHVR EFANFERLVS HKQCTDLLRL SLDQDTDEGV EVLQGRNVYR
AFSSIVDYGE VYRGVKYVVG KGTECAGRVQ LPRSSRGDTW LDVPLSDSFS QVGGVWVNLM
TDLPSSDMFI ATGCELSMRS PRAPPREDAD VWHVYARHSR QGDKAIMTDL FVFDAVSGQL
VEIMLGVQYM RVAKASMSMM LARMTKDDSV LRTKALVPGP TPAAAFQAAL KTAPEVRASS
EPGAKVKASK TSKKEKKEKK PVTKAKSKSS KPSGWRDITE EVRNLVATVS GIDASELELD
AEMADFGIDS LMGMELGKEV EAAFKCTLDQ NEQMEATSLR KFVQCVSNAL FGPNAGPAEA
EDDEDEEKSD NSSSESASES DDAGSESSDT GILTPTGEEE QPLPLKAVAI HKSAGLAAIA
PPVESRLALS SSDILASFGQ VKMQTDTLMK EYGVDKTEGV MLSGSNRLCT ALVVEAMDEL
GCPLRTASPG QPLARVAFLP QHGRLMQWVY EFLERDARLI NIDPASGQIT RTHITAPRKT
SQVILQEVLA SDPGFAVPNR LAYYAGQQLA GVLSGSTDGI RVLFGSPEGR ELTAAMYCEH
TFNCMSYAQM REVTNLLAER IGRTGETLKV LEMGAGTGGT TLIMAPFLAT LAESGALPIE
YTFTDISPSM VANARRRFSK QYPFMRFAVH DIEKPPADEL RNQHLVLASN AIHATHNLGV
SLSNIHQALR PDGFLMMLEM TEVVPFVDLV FGLLEGWWLF DDGRHHAVVP AEHWESELHR
AGFGHVDWTD GNLPENTFQK VIIALASGAQ GARLPKPGPV QTLIPELNRE NVEARTATAE
SLVAKYTAGW ETPKLRALAS RAEKESGKTQ APHAAPGRRA HEAVVIVTGA TGSLGSHIVQ
RLAETPSVAT VVCLNRRSSS TTPEKRQQAA LTARGITLSP GARAKLRVLE TDTSKPQLGL
PPLEYGWLLE NATDIIHNAW PMSGTRPVSA FEPQLQAMRN LLDLARDIAE RPFNGSSRVG
FQFISSIGVV GFCGQSRVSE DRVPLSAALP SGYGEAKWIC ERMVDETLHR HPGLFRAMVV
RPGQISGSST SGFWNPVEHF AFLVKSSQSL RAWPDLQGQM QWIPVDYCAA GVVDLLHLTS
RGDEAYPVYH MDNPVGQNWQ AMNHVLASAL DIPASNIIPF KTWISRVRRS PLPMETENPA
ARLVDFLDDH FERMSCGGLV LDTSKAKEHS TTMAGVGPVG TELARLQYQA RSSLLISLEK
LQCVYHSVAN YSVLVTMGLR RRSSIATPYT PQI
