HEXA_DOTSE
ID HEXA_DOTSE Reviewed; 325 AA.
AC A7TUG9;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 48.
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};
DE Flags: Fragment;
GN Name=hexA {ECO:0000303|PubMed:17683963};
OS Dothistroma septosporum (Red band needle blight fungus) (Mycosphaerella
OS pini).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetidae; Mycosphaerellales; Mycosphaerellaceae; Dothistroma.
OX NCBI_TaxID=64363;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=NZE7;
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 [2]
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 [3]
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 [4]
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 [5]
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 [6]
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 [7]
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; EF177826; ABU23831.1; -; Genomic_DNA.
DR AlphaFoldDB; A7TUG9; -.
DR SMR; A7TUG9; -.
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:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
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; IPR004568; Ppantetheine-prot_Trfase_dom.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF01648; ACPS; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF56214; SSF56214; 1.
DR TIGRFAMs; TIGR00556; pantethn_trn; 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; Transferase.
FT CHAIN <1..325
FT /note="Fatty acid synthase alpha subunit hexA"
FT /id="PRO_0000443459"
FT BINDING 209..211
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 209
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 255..265
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 279..282
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 301..303
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT BINDING 302
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P19097"
FT NON_TER 1
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 35522 MW; 78985CE1D19AB0A2 CRC64;
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 DNAPQGQAGR KAGLEDIQLS
ISHGEDCLIA VAIGIAGNGP AKYTL
