NOR1_DOTSN
ID NOR1_DOTSN Reviewed; 268 AA.
AC M2Y1A3;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Norsolorinic acid ketoreductase nor1 {ECO:0000250|UniProtKB:Q00278};
DE EC=1.1.1.349 {ECO:0000250|UniProtKB:Q00278};
DE AltName: Full=Dothistromin biosynthesis ketoreductase nor1 {ECO:0000303|PubMed:23207690};
DE AltName: Full=Short chain dehydrogenase nor1 {ECO:0000305};
GN Name=Nor1 {ECO:0000303|PubMed:23207690}; ORFNames=DOTSEDRAFT_75691;
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).
CC -!- FUNCTION: Norsolorinic acid ketoreductase; part of the fragmented gene
CC 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:Q00278,
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=(1'S)-averantin + NADP(+) = H(+) + NADPH + norsolorinic acid;
CC Xref=Rhea:RHEA:35447, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:71533, ChEBI:CHEBI:77899;
CC EC=1.1.1.349; Evidence={ECO:0000250|UniProtKB:Q00278};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q00278}. Vacuole {ECO:0000250|UniProtKB:Q00278}.
CC -!- INDUCTION: Expression is positively regulated by the dothistromin-
CC specific transcription factor aflR (PubMed:23207690).
CC {ECO:0000269|PubMed:23207690}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KB446546; EME39084.1; -; Genomic_DNA.
DR AlphaFoldDB; M2Y1A3; -.
DR SMR; M2Y1A3; -.
DR STRING; 675120.M2Y1A3; -.
DR EnsemblFungi; EME39084; EME39084; DOTSEDRAFT_75691.
DR eggNOG; KOG1611; Eukaryota.
DR HOGENOM; CLU_010194_9_1_1; -.
DR OMA; FHFENKW; -.
DR OrthoDB; 1259665at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell.
DR GO; GO:0140393; F:norsolorinic acid ketoreductase activity; IEA:UniProtKB-EC.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; NADP; Oxidoreductase; Reference proteome; Vacuole.
FT CHAIN 1..268
FT /note="Norsolorinic acid ketoreductase nor1"
FT /id="PRO_0000443464"
FT ACT_SITE 182
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 29..31
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 53..54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT BINDING 161
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ SEQUENCE 268 AA; 28762 MW; E0355020A56B64E8 CRC64;
MPSFHNTITI GHRPNGDSKR TTYLVTGASR GIGKGLVASF LARPDSTVIA CVRNVASQSK
ALSDLPCAEG SSLIVVKLDC AVETDPASAV EELQSAHNIR HIDVVVANAA IAGAYGPTST
LPLDAVKEHM QINCYSVLLL FQATRPLLEQ AAPGKAKFVF IGAPISTITQ MEECARAPLG
AYGLTKLAAN YLVRKFHFEN KWLMSFVIDP GHVQTDMGDS GARLMGRKEA PTTLQQSVDG
ICARIDEATK EESSGQFLLH EDGSRLPW
