ATNF_EMENI
ID ATNF_EMENI Reviewed; 1659 AA.
AC Q5AV00; A0A1U8QSZ5; C8V3Y5;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=Fatty acid synthase subunit alpha {ECO:0000303|PubMed:26563584};
DE EC=2.3.1.86 {ECO:0000305|PubMed:26563584};
DE AltName: Full=Aspercryptin biosynthesis cluster protein F {ECO:0000303|PubMed:26563584};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase {ECO:0000250|UniProtKB:Q8TGA2};
DE EC=1.1.1.100 {ECO:0000250|UniProtKB:Q8TGA2};
DE AltName: Full=Beta-ketoacyl reductase {ECO:0000250|UniProtKB:Q8TGA2};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase {ECO:0000250|UniProtKB:Q8TGA2};
DE EC=2.3.1.41 {ECO:0000250|UniProtKB:Q8TGA2};
GN Name=atnF {ECO:0000303|PubMed:26563584}; ORFNames=ANIA_07880;
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 IDENTIFICATION OF THE CLUSTER.
RX PubMed=23248299; DOI=10.1073/pnas.1205532110;
RA Andersen M.R., Nielsen J.B., Klitgaard A., Petersen L.M., Zachariasen M.,
RA Hansen T.J., Blicher L.H., Gotfredsen C.H., Larsen T.O., Nielsen K.F.,
RA Mortensen U.H.;
RT "Accurate prediction of secondary metabolite gene clusters in filamentous
RT fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E99-E107(2013).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=27310134; DOI=10.1021/acschembio.6b00398;
RA Henke M.T., Soukup A.A., Goering A.W., McClure R.A., Thomson R.J.,
RA Keller N.P., Kelleher N.L.;
RT "New aspercryptins, lipopeptide natural products, revealed by HDAC
RT inhibition in Aspergillus nidulans.";
RL ACS Chem. Biol. 11:2117-2123(2016).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=26563584; DOI=10.1002/anie.201507097;
RA Chiang Y.M., Ahuja M., Oakley C.E., Entwistle R., Asokan A., Zutz C.,
RA Wang C.C., Oakley B.R.;
RT "Development of genetic dereplication strains in Aspergillus nidulans
RT results in the discovery of aspercryptin.";
RL Angew. Chem. Int. Ed. 55:1662-1665(2016).
CC -!- FUNCTION: Fatty acid synthase subunit alpha; part of the gene cluster
CC that mediates the biosynthesis of aspercryptins, linear lipopeptides
CC built from six amino acids including 2 highly unusual and
CC nonproteogenic amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-
CC dodecanol (2adol) (PubMed:23248299, PubMed:27310134, PubMed:26563584).
CC The core structure of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-
CC 2aoa-Asn-2adol (PubMed:27310134). The first step of aspercryptin
CC biosynthesis is the generation of the fatty acid precursors, octanoic
CC and dodecanoic acids, by the FAS subunits atnF and atnM
CC (PubMed:27310134, PubMed:26563584). The fatty acid precursors are
CC likely transformed into the corresponding alpha-amino fatty acids in
CC three steps (PubMed:27310134, PubMed:26563584). First, they are
CC hydroxylated by the cytochrome P450 monooxygenase atnE, then oxidized
CC to the corresponding alpha-keto acids by the NAD(P)-dependent
CC oxidoreductase atnD, and finally converted to the alpha-amino fatty
CC acids by the PLP-dependent aminotransferases atnH or atnJ
CC (PubMed:27310134, PubMed:26563584). the alpha-amino fatty acids, 2-
CC amino-octanoic and 2-amino-dodecanoic acids, are recognized, activated,
CC and covalently tethered to the NRPS atnA by its fourth and sixth
CC adenylation domains (PubMed:27310134). The second module of atnA is the
CC Thr module and contains an epimerase (E) domain responsible for the
CC epimerization of Thr to D-allo-Thr (PubMed:26563584). Additionally,
CC despite atnA having only one epimerase domain, the first amino acid of
CC aspercryptin A1 is D-Ser, suggesting that serine is either loaded
CC directly as D-Ser on the first module or that the epimerase domain in
CC the threonine module epimerizes both L-Ser and L-Thr (PubMed:27310134).
CC After condensation of the hexapeptide of aspercryptin, the C-terminal
CC reductase (TE) domain might be involved in the reductive release and
CC production of the aldehyde hexapeptide (PubMed:26563584). Further
CC reduction would generate aspercryptins (PubMed:27310134,
CC PubMed:26563584). The variety of aspercryptins produced reflects the
CC flexibiliy of the atnA NRPS, allowing incorporation of alanine instead
CC of serine, valine for isoleucine, and a C10 fatty amino alcohol instead
CC of the C12 version (PubMed:27310134). AtnB seems to be involved in the
CC selectivity for Ile versus Val by the third module (PubMed:26563584).
CC Moreover, type B, C and D aspercryptins have an additional N-terminal
CC cichorine, acetyl and propionyl group respectively (PubMed:27310134).
CC {ECO:0000269|PubMed:23248299, ECO:0000269|PubMed:26563584,
CC ECO:0000269|PubMed:27310134}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 2n H(+) + n malonyl-CoA + 2n NADPH = a long-chain
CC fatty acyl-CoA + n CO2 + n CoA + H2O + 2n NADP(+);
CC Xref=Rhea:RHEA:22896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:83139; EC=2.3.1.86;
CC Evidence={ECO:0000250|UniProtKB:Q8TGA2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-[ACP] + H(+) + malonyl-[ACP] = a 3-oxoacyl-[ACP]
CC + CO2 + holo-[ACP]; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC EC=2.3.1.41; Evidence={ECO:0000255|PROSITE-ProRule:PRU10022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + H(+)
CC + NADPH; Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC Evidence={ECO:0000250|UniProtKB:Q8TGA2};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26563584}.
CC -!- SUBUNIT: [Alpha(6)beta(6)] hexamers of two multifunctional subunits
CC (alpha and beta). {ECO:0000250|UniProtKB:P19097}.
CC -!- INDUCTION: Expression is positively regulated by the aspercryptin
CC cluser-specific transcription factor atnN (PubMed:27310134).
CC {ECO:0000269|PubMed:27310134}.
CC -!- PTM: 4'-phosphopantetheine is transferred from CoA to a specific serine
CC of the acyl carrier domain by the C-terminal PPT domain. This
CC modification is essential for activity because fatty acids are bound in
CC thioester linkage to the sulfhydryl of the prosthetic group.
CC -!- DISRUPTION PHENOTYPE: Eliminates more than 99.5% of aspercryptin
CC production (PubMed:26563584). {ECO:0000269|PubMed:26563584}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Fungal fatty acid
CC synthetase subunit alpha family. {ECO:0000305}.
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DR EMBL; BN001302; CBF73444.1; -; Genomic_DNA.
DR EMBL; AACD01000135; EAA59534.1; -; Genomic_DNA.
DR RefSeq; XP_681149.1; XM_676057.1.
DR AlphaFoldDB; Q5AV00; -.
DR SMR; Q5AV00; -.
DR STRING; 162425.CADANIAP00003896; -.
DR EnsemblFungi; CBF73444; CBF73444; ANIA_07880.
DR EnsemblFungi; EAA59534; EAA59534; AN7880.2.
DR GeneID; 2869007; -.
DR KEGG; ani:AN7880.2; -.
DR eggNOG; ENOG502QQJX; Eukaryota.
DR HOGENOM; CLU_000114_0_0_1; -.
DR InParanoid; Q5AV00; -.
DR OMA; ELMAYQF; -.
DR OrthoDB; 39339at2759; -.
DR Proteomes; UP000000560; Chromosome II.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005835; C:fatty acid synthase complex; IBA:GO_Central.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR040899; Fas_alpha_ACP.
DR InterPro; IPR026025; FAS_alpha_yeast.
DR InterPro; IPR041550; FASI_helical.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF18325; Fas_alpha_ACP; 1.
DR Pfam; PF18314; FAS_I_H; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR PIRSF; PIRSF000454; FAS_yeast_alpha; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1659
FT /note="Fatty acid synthase subunit alpha"
FT /id="PRO_0000444129"
FT DOMAIN 160..235
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 114..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 588..826
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2"
FT REGION 934..1564
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2"
FT REGION 1631..1659
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 114..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1634..1659
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 195
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1659 AA; 181995 MW; 572041ADC2308725 CRC64;
MVAAQDDGAQ RKLAHTLLLE LMSYQFASPV RWIETQDVVL GQYRAERIIE IGPAATLTNM
IKQTVQSKFL HSDRASLLQR QLLASEKQGK DIYYEDDGVG IGTGAEAPAP SAKTQAQASG
GAGTIAGAGS STAPVTAPPA PAAAKAVPAG GMQAIEDRQA QAFEIVRTLL SRILKIALTD
VVGTQSIKSL SGGRSTLENE IIGDLASEFG SLPDRAEDLT VNDLSAALQK TFTGQMRKVI
LKMLHAMFAS KMPGQFTVAT ARTYLHSRWG LGSGRQDSVL LLAIAQQPGS RLKEEAEARS
FFDGLVQFYA DEHGLTLGAN SGAADETSGL GGGLVMDQKT LAALTGGQQE LSKALLKIYA
KHLDIDLDGD RRALHDLQAT VEKDLRLALD QIHQELGEDF TDGVQPVFSA RKARRFDSAW
SWALQDLLQL YYEVSRTGGE TEVDLAAKRC KHIEDAADPR LLDVLQRIVG RFEQQPVLSS
MFTQLAQRCR DSLLHGPRYL ARPDQQGPRT TISAEGDITY TEQERAEPVP LADLVYLPKS
TEAAPLEPFL HLKQRTGGSS AWTYSHDLTE QYRAVLEQAT TVGESFAGRS VLITGAGVGS
IGAEVLKGLL AGGARVIVTT SRFSSSVVRK YQDLYTQVGS RGSELVVVPF NQASVQDVTA
LVNYIYDAQG GLHWDLDHIL PFAAMPENGR TIEKIDPHSE LAHRTMMVNT LRLLGAVKAR
KEAQGSRTRP TQVILPLSPN HGVFGGDGLY SESKLGLEAL FNRWHSEDWS DYLSVCGAVI
GWTRGTGLMS GNNLVAEGIE ELGCRTFSQQ EMAQCLLCLM FNTMCSLCEE APLYADLSGR
MGAVQNLRQK VQELRTEINE TANTRRALLE ELAMEARCSE GPTPTIDSEP AKATATPTLT
AHVRLDFPPT VDYNQEIKPL TADLQGMVDL DRVVVVTGFG EIGPWGNART RWEMEAYGEF
SLEGCVEMAW LMGLIRYENS SSPGWVDAKT NERVHDHEVK HKYEEHILSH TGIRLIEPDR
FGANYHPEHK QLLHEVLIQE DFPELEVPEA TAQQMKLEHG NKVDIIPDPE GGDQCRVVLK
KGAKLMVPKA LRLDRMVIGQ IPTGWDARKY GIPEDVISQV DPVTLYMLAC SIEALLSSGI
TDPYEIYRYI HVSEAGNCVG SSLGGFNSLQ QMYRGRYMEK EVQKDILQET FVNTIGAWMN
MLLMSSAGPI RTPVGACATA IESVELGYDT LISGKAKFCF VGGGDDFGEE VLYEFANMKA
TANTVDEFEQ GREASEMSRP AASTRNGFME SHGCGVQILT TARLAIEMGL PVRGVIAFVE
TSSDKASRSV PAPGRGILSK AREVRSSSPS SSLISSPLLN ISNRRKRLDF RKKQIEFARE
TALEELQLEI AHVEESEVED YIRERTAQIN AEAQKDLRNA QYHLGNAFWQ NDPSIAPLRG
ALAVWGLTID DLDVASFHGT STKLNEKNEC SLIQAQLSHL GRAKGNVILG VFQKYLTGHP
KGAAGAWMLN GALQILDTGI VPGNRNLDNV EAELQKNEQI AFLNRSLDTG RGSMRAVSVT
SFGFGQKGAQ TIVVHPKYLF ATLEEQEYEE YLDKRAKRQK KADSFFYRGL ASNRLFELKT
APPWAPQKEL ETLLDPTPPQ TNVDDRVARS IVQQESAEP
