HEXA_DOTSN
ID HEXA_DOTSN Reviewed; 1692 AA.
AC M2YJJ3;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Fatty acid synthase alpha subunit hexA {ECO:0000250|UniProtKB:P19097};
DE EC=2.3.1.86 {ECO:0000250|UniProtKB:P19097};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase {ECO:0000250|UniProtKB:P19097};
DE EC=1.1.1.100 {ECO:0000250|UniProtKB:P19097};
DE AltName: Full=Beta-ketoacyl reductase {ECO:0000250|UniProtKB:Q8TGA2};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase {ECO:0000250|UniProtKB:P19097};
DE EC=2.3.1.41 {ECO:0000250|UniProtKB:P19097};
DE AltName: Full=Dothistromin biosynthesis protein hexA {ECO:0000303|PubMed:17683963};
GN Name=hexA {ECO:0000303|PubMed:17683963}; ORFNames=DOTSEDRAFT_66976;
OS Dothistroma septosporum (strain NZE10 / CBS 128990) (Red band needle blight
OS fungus) (Mycosphaerella pini).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetidae; Mycosphaerellales; Mycosphaerellaceae; Dothistroma.
OX NCBI_TaxID=675120;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23209441; DOI=10.1371/journal.pgen.1003088;
RA de Wit P.J.G.M., van der Burgt A., Oekmen B., Stergiopoulos I.,
RA Abd-Elsalam K.A., Aerts A.L., Bahkali A.H., Beenen H.G., Chettri P.,
RA Cox M.P., Datema E., de Vries R.P., Dhillon B., Ganley A.R.,
RA Griffiths S.A., Guo Y., Hamelin R.C., Henrissat B., Kabir M.S.,
RA Jashni M.K., Kema G., Klaubauf S., Lapidus A., Levasseur A., Lindquist E.,
RA Mehrabi R., Ohm R.A., Owen T.J., Salamov A., Schwelm A., Schijlen E.,
RA Sun H., van den Burg H.A., van Ham R.C.H.J., Zhang S., Goodwin S.B.,
RA Grigoriev I.V., Collemare J., Bradshaw R.E.;
RT "The genomes of the fungal plant pathogens Cladosporium fulvum and
RT Dothistroma septosporum reveal adaptation to different hosts and lifestyles
RT but also signatures of common ancestry.";
RL PLoS Genet. 8:E1003088-E1003088(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23236275; DOI=10.1371/journal.ppat.1003037;
RA Ohm R.A., Feau N., Henrissat B., Schoch C.L., Horwitz B.A., Barry K.W.,
RA Condon B.J., Copeland A.C., Dhillon B., Glaser F., Hesse C.N., Kosti I.,
RA LaButti K., Lindquist E.A., Lucas S., Salamov A.A., Bradshaw R.E.,
RA Ciuffetti L., Hamelin R.C., Kema G.H.J., Lawrence C., Scott J.A.,
RA Spatafora J.W., Turgeon B.G., de Wit P.J.G.M., Zhong S., Goodwin S.B.,
RA Grigoriev I.V.;
RT "Diverse lifestyles and strategies of plant pathogenesis encoded in the
RT genomes of eighteen Dothideomycetes fungi.";
RL PLoS Pathog. 8:E1003037-E1003037(2012).
RN [3]
RP FUNCTION.
RX PubMed=12039746; DOI=10.1128/aem.68.6.2885-2892.2002;
RA Bradshaw R.E., Bhatnagar D., Ganley R.J., Gillman C.J., Monahan B.J.,
RA Seconi J.M.;
RT "Dothistroma pini, a forest pathogen, contains homologs of aflatoxin
RT biosynthetic pathway genes.";
RL Appl. Environ. Microbiol. 68:2885-2892(2002).
RN [4]
RP FUNCTION.
RX PubMed=16649078; DOI=10.1007/s11046-006-0240-5;
RA Bradshaw R.E., Jin H., Morgan B.S., Schwelm A., Teddy O.R., Young C.A.,
RA Zhang S.;
RT "A polyketide synthase gene required for biosynthesis of the aflatoxin-like
RT toxin, dothistromin.";
RL Mycopathologia 161:283-294(2006).
RN [5]
RP FUNCTION.
RX PubMed=17683963; DOI=10.1016/j.fgb.2007.06.005;
RA Zhang S., Schwelm A., Jin H., Collins L.J., Bradshaw R.E.;
RT "A fragmented aflatoxin-like gene cluster in the forest pathogen
RT Dothistroma septosporum.";
RL Fungal Genet. Biol. 44:1342-1354(2007).
RN [6]
RP REVIEW ON FUNCTION, AND PATHWAY.
RX PubMed=22069571; DOI=10.3390/toxins2112680;
RA Schwelm A., Bradshaw R.E.;
RT "Genetics of dothistromin biosynthesis of Dothistroma septosporum: an
RT update.";
RL Toxins 2:2680-2698(2010).
RN [7]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=23207690; DOI=10.1016/j.fgb.2012.11.006;
RA Chettri P., Ehrlich K.C., Cary J.W., Collemare J., Cox M.P.,
RA Griffiths S.A., Olson M.A., de Wit P.J., Bradshaw R.E.;
RT "Dothistromin genes at multiple separate loci are regulated by AflR.";
RL Fungal Genet. Biol. 51:12-20(2013).
RN [8]
RP FUNCTION.
RX PubMed=23448391; DOI=10.1111/nph.12161;
RA Bradshaw R.E., Slot J.C., Moore G.G., Chettri P., de Wit P.J.,
RA Ehrlich K.C., Ganley A.R., Olson M.A., Rokas A., Carbone I., Cox M.P.;
RT "Fragmentation of an aflatoxin-like gene cluster in a forest pathogen.";
RL New Phytol. 198:525-535(2013).
RN [9]
RP INDUCTION.
RX PubMed=25986547; DOI=10.1016/j.funbio.2015.01.007;
RA Chettri P., Ehrlich K.C., Bradshaw R.E.;
RT "Regulation of the aflatoxin-like toxin dothistromin by AflJ.";
RL Fungal Biol. 119:503-508(2015).
CC -!- FUNCTION: Fatty acid synthase alpha subunit; part of the fragmented
CC gene cluster that mediates the biosynthesis of dothistromin (DOTH), a
CC polyketide toxin very similar in structure to the aflatoxin precursor,
CC versicolorin B (PubMed:12039746, PubMed:17683963, PubMed:22069571,
CC PubMed:23207690, PubMed:23448391). The first step of the pathway is the
CC conversion of acetate to norsolorinic acid (NOR) and requires the fatty
CC acid synthase subunits hexA and hexB, as well as the polyketide
CC synthase pksA (PubMed:16649078, PubMed:23207690). PksA combines a
CC hexanoyl starter unit and 7 malonyl-CoA extender units to synthesize
CC the precursor NOR (By similarity). The hexanoyl starter unit is
CC provided to the acyl-carrier protein (ACP) domain by the fungal fatty
CC acid synthase hexA/hexB (By similarity). The second step is the
CC conversion of NOR to averantin (AVN) and requires the norsolorinic acid
CC ketoreductase nor1, which catalyzes the dehydration of norsolorinic
CC acid to form (1'S)-averantin (PubMed:23207690). The cytochrome P450
CC monooxygenase avnA then catalyzes the hydroxylation of AVN to
CC 5'hydroxyaverantin (HAVN) (PubMed:23207690). The next step is performed
CC by adhA that transforms HAVN to averufin (AVF) (PubMed:23207690).
CC Averufin might then be converted to hydroxyversicolorone by cypX and
CC avfA (PubMed:23207690). Hydroxyversicolorone is further converted
CC versiconal hemiacetal acetate (VHA) by moxY (PubMed:23207690). VHA is
CC then the substrate for the versiconal hemiacetal acetate esterase est1
CC to yield versiconal (VAL) (PubMed:23207690). Versicolorin B synthase
CC vbsA then converts VAL to versicolorin B (VERB) by closing the bisfuran
CC ring (PubMed:16649078, PubMed:23207690). Then, the activity of the
CC versicolorin B desaturase verB leads to versicolorin A (VERA)
CC (PubMed:23207690). DotB, a predicted chloroperoxidase, may perform
CC epoxidation of the A-ring of VERA (PubMed:23207690). Alternatively, a
CC cytochrome P450, such as cypX or avnA could catalyze this step
CC (PubMed:23207690). It is also possible that another, uncharacterized,
CC cytochrome P450 enzyme is responsible for this step (PubMed:23207690).
CC Opening of the epoxide could potentially be achieved by the epoxide
CC hydrolase epoA (PubMed:23207690). However, epoA seems not to be
CC required for DOTH biosynthesis, but other epoxide hydrolases may have
CC the ability to complement this hydrolysis (PubMed:23207690).
CC Alternatively, opening of the epoxide ring could be achieved non-
CC enzymatically (PubMed:23207690). The next step is the deoxygenation of
CC ring A to yield the 5,8-dihydroxyanthraquinone which is most likely
CC catalyzed by the NADPH dehydrogenase encoded by ver1 (PubMed:23207690).
CC The last stages of DOTH biosynthesis are proposed to involve
CC hydroxylation of the bisfuran (PubMed:23207690). OrdB and norB might
CC have oxidative roles here (PubMed:23207690). An alternative possibility
CC is that cytochrome P450 monoogenases such as avnA and cypX might
CC perform these steps in addition to previously proposed steps
CC (PubMed:23207690). {ECO:0000250|UniProtKB:Q12437,
CC ECO:0000269|PubMed:12039746, ECO:0000269|PubMed:16649078,
CC ECO:0000303|PubMed:22069571, ECO:0000305|PubMed:17683963,
CC ECO:0000305|PubMed:23207690, ECO:0000305|PubMed:23448391}.
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:P19097};
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:P19097};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
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 dothistromin-
CC specific transcription factors aflR and aflJ (PubMed:23207690,
CC PubMed:25986547). {ECO:0000269|PubMed:23207690,
CC ECO:0000269|PubMed:25986547}.
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 {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Fungal fatty acid
CC synthetase subunit alpha family. {ECO:0000305}.
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DR EMBL; KB446546; EME39096.1; -; Genomic_DNA.
DR AlphaFoldDB; M2YJJ3; -.
DR SMR; M2YJJ3; -.
DR STRING; 675120.M2YJJ3; -.
DR EnsemblFungi; EME39096; EME39096; DOTSEDRAFT_66976.
DR eggNOG; ENOG502RV4X; Eukaryota.
DR HOGENOM; CLU_000114_0_0_1; -.
DR OMA; VGVAPKY; -.
DR OrthoDB; 39339at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
DR GO; GO:0005835; C:fatty acid synthase complex; IEA:InterPro.
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:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.90.470.20; -; 1.
DR InterPro; IPR008278; 4-PPantetheinyl_Trfase_dom.
DR InterPro; IPR037143; 4-PPantetheinyl_Trfase_dom_sf.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR004568; Ppantetheine-prot_Trfase_dom.
DR InterPro; IPR002347; SDR_fam.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF01648; ACPS; 1.
DR Pfam; PF00106; adh_short; 1.
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 SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR SUPFAM; SSF56214; SSF56214; 1.
DR TIGRFAMs; TIGR00556; pantethn_trn; 1.
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; Magnesium; Metal-binding; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1692
FT /note="Fatty acid synthase alpha subunit hexA"
FT /id="PRO_0000443458"
FT DOMAIN 90..174
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 44..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..746
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2, ECO:0000255"
FT REGION 954..1419
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2, ECO:0000255"
FT REGION 1263..1287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1135
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1569..1571
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 1569
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 1615..1625
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 1639..1642
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 1668..1670
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 1669
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT MOD_RES 125
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1692 AA; 183262 MW; B556CA38EFA88391 CRC64;
MGQKTIKRKI QSAERPAEAD VAFLASTQHS KDLCYEYDAP EEVAVEEPVD ETPAPETAPE
RPPLSRAKTA AVKPQETAAP TTATIADVPL SAEEIVRALV ARKLKKPILS IPTSKSVKEL
CNGKSTLQNE IVGDFHSEFT NLPDRPEDIP LKELVPASQS LMLGRVSSAL LSKLVSSKMP
ARFNADAIGK YLASKWGLGP LRSVAVMLFA IAAEPEARLG SVAAAEKYLD DTAAKYAEWA
GITLQERSTQ SSAGGGGSSG TVDPTVLAEL TKTNTRLAKR QFQALAEYLQ VDLMKPSSEQ
ESEALAVELQ QKLDAWTAEF SEEFLAGVAP TFSEKKSRRY NAWWNAARQD VLALFSGNLQ
EDLSRDAAAL EAFLDRLSNR AGESLLAMTR SLSRRNQANA IPGLTDIARR AEKAISSCID
RPATAKVHLP ATRPRTTVSD EGDIKFNEVP RPDVSGHAAY ADVLQAKDLN GHPAAARFVS
LKSAHSHTDL TNGMLDRIRT ALDSGMSFAG KNILITGAGQ GSIGAEVVRI LLTGGARVIV
TTSREPSSTA KYFQQMYEES GAKGSELILT RFNQASAKDC ENLVDHIYDS SGLDRDLDAV
LPFAAAPEGG TEIQDVGAKN ELVHRLMLAS VFRMLGRVIK NKRDRSIDCH PTQVLLPLSP
NHGTFGGDGM YAESKLGLES LVNRVQSESW SDELAICGVK IGWTRGTGLM NANDIVAEAI
EDHGVLTFSV QEMAFNIAML MTPELVDLCE NAPLMADFGG GLSALEDCAK ILSAARTEIN
TAADVARAVK AEDDLERAAS RTLPAPSSTS PVAKKSMLRI GFPRLPDFEL ELSPLEHLRD
IKDPSETVVV VGFSELGPWG SARLRWEIES KGDFSQVGYM EMAWMMDLIK HVDGPTKNGY
YVGWVDSKTG ESVHDAEIEA RYGEVIRKHS GIRFVDPEGS AGYDPSKKEY LHEVAVEEDL
PEFEASSATA EAFRLRHGTN VSISPIEGTE NCRVQVKRGA SIKIPKSVPF TWGSVAGQLP
KGWSPKKYGI PEDLIPQLDP VSLYTICCVA EAFYSAGITD PLEIFKYIHL SEIGNFLGSS
MGGALKTRQM YRDIYLDKDI QSDVLQETYL NTTGAWVNML LLGSTGPIKT PMGACATGVE
SIDSAFESIM SDKTRMCIVG GFDDFHEDES YGFSTMKATV NVEEELAKGR LPSEMSRPTA
ESRSGFVEAH GCGVQILCRG DVALEMGLPV YGIIAGSTMA ADKVGRSVPA PGQGILTFAR
ETGQAQLDKS SPSTNTTSRT SSVSLARRGA TVSPLRASLD AWGLTIDDLD VASLHGTSTK
ANDLNEPEVI CKQMDHLGRT PGRPLWAICQ KSVTGHPKAP AAAWMLNGCL QVMDSRTIPA
NRNADNVDPA LQTATHLCFP TRPVRVQDVR AFILTSFGFG QKGGQVVGVA PKYFFATLDE
EVYKDYSVRV TKRSKTADRA YAKALMSNAI VKVQDHSPYE QEDQSRIFMD PLSRITEDAE
TGSYHFDTKD IRNVADVKAR LTRLVRGERL NARPDAASGL AQAARSAQAW IEKQTGGRSS
VDTSTVGIDL VDLSAFSAHE NETFIERNFT EQEKAFAKQS LDQKMAFASR WAAKEAVFKC
LHTQTKGAGA AMKDIEIVKS DNAPKVKLHN DCIKAGRKAG LEDIQLSISH GEDCLIAVAI
GIAGNGPAKY TL
