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 27-MAR-2024, entry version 36. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; NCTVIAA; -. DR OrthoDB; 1703151at2759; -. 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 CDD; cd05325; carb_red_sniffer_like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43544; SHORT-CHAIN DEHYDROGENASE/REDUCTASE; 1. DR PANTHER; PTHR43544:SF12; ZGC:65997; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 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 /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:O93868" FT ACT_SITE 186 FT /note="Lowers pKa of active site Tyr" FT /evidence="ECO:0000250|UniProtKB:O93868" FT BINDING 32 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:L0E2Z4" FT BINDING 79 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:L0E2Z4" FT BINDING 108 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O93868" FT BINDING 182 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O93868" FT BINDING 186 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O93868" FT BINDING 213 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:O93868" FT BINDING 215 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:L0E2Z4" 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 //