VBSA_DOTSN
ID VBSA_DOTSN Reviewed; 647 AA.
AC M2Y151;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Versicolorin B synthase {ECO:0000250|UniProtKB:Q12062};
DE EC=4.2.1.143 {ECO:0000250|UniProtKB:Q12062};
DE AltName: Full=5'-oxoaverantin cyclase {ECO:0000250|UniProtKB:Q12062};
DE EC=4.2.1.142 {ECO:0000250|UniProtKB:Q12062};
DE AltName: Full=Dothistromin biosynthesis protein vbsA {ECO:0000303|PubMed:17683963};
DE Flags: Precursor;
GN Name=vbsA {ECO:0000303|PubMed:17683963}; ORFNames=DOTSEDRAFT_75656;
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.
RC STRAIN=ATCC MYA-605;
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 DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION.
RC STRAIN=ATCC MYA-605;
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 INDUCTION.
RX PubMed=18262779; DOI=10.1016/j.mycres.2007.03.018;
RA Schwelm A., Barron N.J., Zhang S., Bradshaw R.E.;
RT "Early expression of aflatoxin-like dothistromin genes in the forest
RT pathogen Dothistroma septosporum.";
RL Mycol. Res. 112:138-146(2008).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=22069539; DOI=10.3390/toxins1020173;
RA Bradshaw R.E., Feng Z., Schwelm A., Yang Y., Zhang S.;
RT "Functional analysis of a putative dothistromin toxin MFS transporter
RT gene.";
RL Toxins 1:173-187(2009).
RN [8]
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 [9]
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 [10]
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 [11]
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: Versicolorin B synthase; part of the fragmented gene cluster
CC that mediates the biosynthesis of dothistromin (DOTH), a polyketide
CC 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:Q12062,
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=(2S-3S)-versiconal hemiacetal = H2O + versicolorin B;
CC Xref=Rhea:RHEA:33859, ChEBI:CHEBI:15377, ChEBI:CHEBI:77950,
CC ChEBI:CHEBI:77951; EC=4.2.1.143;
CC Evidence={ECO:0000250|UniProtKB:Q12062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-5'-oxoaverantin + H(+) = (1'S,5'S)-averufin + H2O;
CC Xref=Rhea:RHEA:35671, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:71537, ChEBI:CHEBI:77933; EC=4.2.1.142;
CC Evidence={ECO:0000250|UniProtKB:Q12062};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E4QP00};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12062}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q12062}.
CC -!- INDUCTION: Expression is positively regulated by the dothistromin-
CC specific transcription factors aflR and aflJ (PubMed:23207690,
CC PubMed:25986547). Dothistromin biosynthetic proteins are co-regulated,
CC showing a high level of expression at ealy exponential phase with a
CC subsequent decline in older cultures (PubMed:17683963,
CC PubMed:18262779). {ECO:0000269|PubMed:17683963,
CC ECO:0000269|PubMed:18262779, ECO:0000269|PubMed:23207690,
CC ECO:0000269|PubMed:25986547}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of dothistromin
CC (PubMed:18262779). {ECO:0000269|PubMed:17683963}.
CC -!- SIMILARITY: Belongs to the GMC oxidoreductase family. {ECO:0000305}.
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DR EMBL; KB446546; EME39034.1; -; Genomic_DNA.
DR AlphaFoldDB; M2Y151; -.
DR SMR; M2Y151; -.
DR STRING; 675120.M2Y151; -.
DR EnsemblFungi; EME39034; EME39034; DOTSEDRAFT_75656.
DR eggNOG; KOG1238; Eukaryota.
DR HOGENOM; CLU_002865_6_3_1; -.
DR OMA; REMFYMQ; -.
DR OrthoDB; 798314at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR GO; GO:0046572; F:versicolorin B synthase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; FAD; Flavoprotein; Glycoprotein; Lyase; Reference proteome;
KW Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..647
FT /note="Versicolorin B synthase"
FT /id="PRO_5004029179"
FT BINDING 85..86
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 106..107
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 172..175
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 617
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 628..629
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 509
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 647 AA; 70966 MW; F4A8C18293AC9368 CRC64;
MALSTILTAA AMPVAGLFAF AQQSSAFFDQ IPVLGSMLNS PVGTYDAQAA QMDGRIQARD
LLSSHFGPVG WPHQSFDYVI VGGGTAGLAM AKRLSEEEGN SVALIEAGGF YEMDAGNATE
VPMYLFNYFF DNGYMKNPLF DWYQYTEPQE GLHNREMFYM QGKTLGGSTA RGAMLYHRGS
KGAYQKWADE VGDDSYTWEK WLPHFQRGIK FSGPNTNPRP ANATAVNDDK AWSASGGPVH
VAYPYLTNAI SSWVDKALDS FGFSNVQGFS NGVLLGKSYI THTINPFTRR RETASSSYLR
EALVESNNLN IYIRTLAKKV LFDENKKANA VEVQTDGFKW KIEAKKEVIL SAGVMRSPQL
LMVSGIGPKE TLEKLDIPVL SDRPGVGQNM QDTIILGPTN PIRVESHSQL LGGKDTLPRS
IDDYNNHRTG LLTNPGQDFF AFEKHAEEGP GSLSKETAAD IDANFPADWP TYSFIALDDT
FVPQFNGKNY FSMSAALMTT FSRGYVSINS TDTLDNPIVD PKWLSDPRDQ EMAVAAFRRC
RQFTQHEILQ DVIDGEELLP GKKYQTDDEV LGYIAETSDA YYAGVGTAAM GKKDDPKAVL
DSKARVLGVQ GLRVVDASSF PFAIDGQPMG TVYALAEKIA ADIIAGN
