MOXY_DOTSE
ID MOXY_DOTSE Reviewed; 626 AA.
AC Q30DW9;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=FAD-binding monooxygenase moxY {ECO:0000305};
DE EC=1.14.13.- {ECO:0000305};
DE AltName: Full=Dothistromin biosynthesis protein moxY {ECO:0000303|PubMed:23207690};
GN Name=moxY {ECO:0000303|PubMed:23207690};
GN Synonyms=moxA {ECO:0000303|PubMed:16649078};
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].
RC STRAIN=NZE7;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NZE1 / ATCC MYA-605;
RA Zhang S., Bradshaw R.E.;
RL Submitted (JUL-2010) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
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 [6]
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 [7]
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: FAD-binding monooxygenase; 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:Q6UEF3,
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000303|PubMed:22069571,
CC ECO:0000305|PubMed:23207690}.
CC -!- INDUCTION: Expression is positively regulated by the dothistromin-
CC specific transcription factor aflR (PubMed:23207690). Dothistromin
CC biosynthetic proteins are co-regulated, showing a high level of
CC expression at ealy exponential phase with a subsequent decline in older
CC cultures (PubMed:17683963). {ECO:0000269|PubMed:17683963,
CC ECO:0000269|PubMed:23207690}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; DQ149246; AAZ95013.1; -; Genomic_DNA.
DR AlphaFoldDB; Q30DW9; -.
DR SMR; Q30DW9; -.
DR OMA; PRQDITD; -.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR020946; Flavin_mOase-like.
DR Pfam; PF00743; FMO-like; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 2: Evidence at transcript level;
KW FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase.
FT CHAIN 1..626
FT /note="FAD-binding monooxygenase moxY"
FT /id="PRO_0000443475"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 96..99
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 106..108
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 108..109
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 114
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 243..249
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 266..267
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 359
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 626 AA; 71572 MW; 9C4C29E5CC60C89E CRC64;
MAPFLSAHGE SASSSSSSSP TPSRHTRNQH VDYSTPGSTG YNIPQNTTWN APSNRKIRVL
TIGAGISGIL MAYQLQKHCE NVEHVVYEKN EDVGGTWLEN RYPRAGCDIP SHAYTYQFAL
NPDWPRFFSF APDIWAYLNK VCETFDLKKY MRFHVEVVGC YWQEHAGEWV VKLREHLPNH
EVREFEDRCN VLLYGAGVLN NFKFPDIPGL QDRFKGRVIH TARWPKDYKE EDWAKERVAV
IGSGASSIQT VPGMQPYAKH LDIFVRTGVW FGVIAGNSGS QAKEYSEEER ENFRRDPKAV
VAHAREIEEQ VNGMWGGFYA GSMGQKMGSG YFRTRMAEHI KDERLLQGFS PKFGLGCRRI
TPGDPYMEAI QKENVDVHFT PVESCTEKGV VGGDGVEREV DTVICATGFD VSYRPRFPVI
GKDGVDLREK WDLCPESYLG LAIPDMPNFL TFIGPTWPIE NGSVMAPLHS VSEYAIQLIK
RMQNENIRSW VPRQDITDSF NDHVQEWIKH TVWKDDCRSW YKNNETGRVN AIWPGSSLHY
QQVIERPRYE DFEIHSFNDN PWAHLGMGWT VQDRKGPKEE DVCPYFNVKN IDPKWYEACG
GDSRLLVERP EESSQAGQQF LWPTGT
