VDTE1_BYSSP
ID VDTE1_BYSSP Reviewed; 571 AA.
AC A0A443HK11;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=FAD-binding monooxygenase VdtE {ECO:0000303|PubMed:31304040};
DE EC=1.14.13.- {ECO:0000269|PubMed:31045362};
DE AltName: Full=Viriditoxin biosynthesis cluster protein E {ECO:0000303|PubMed:31304040};
GN Name=VdtE {ECO:0000303|PubMed:31304040}; ORFNames=C8Q69DRAFT_480056;
OS Byssochlamys spectabilis (Paecilomyces variotii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Thermoascaceae; Paecilomyces.
OX NCBI_TaxID=264951;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 101075;
RX PubMed=30619145; DOI=10.3389/fmicb.2018.03058;
RA Urquhart A.S., Mondo S.J., Maekelae M.R., Hane J.K., Wiebenga A., He G.,
RA Mihaltcheva S., Pangilinan J., Lipzen A., Barry K., de Vries R.P.,
RA Grigoriev I.V., Idnurm A.;
RT "Genomic and genetic insights into a cosmopolitan fungus, Paecilomyces
RT variotii (Eurotiales).";
RL Front. Microbiol. 9:3058-3058(2018).
RN [2]
RP IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=31304040; DOI=10.1186/s40694-019-0072-y;
RA Urquhart A.S., Hu J., Chooi Y.H., Idnurm A.;
RT "The fungal gene cluster for biosynthesis of the antibacterial agent
RT viriditoxin.";
RL Fungal Biol. Biotechnol. 6:2-2(2019).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31045362; DOI=10.1021/jacs.9b03354;
RA Hu J., Li H., Chooi Y.H.;
RT "Fungal dirigent protein controls the stereoselectivity of multicopper
RT oxidase-catalyzed phenol coupling in viriditoxin biosynthesis.";
RL J. Am. Chem. Soc. 141:8068-8072(2019).
CC -!- FUNCTION: FAD-binding monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of viriditoxin, one of the 'classical'
CC secondary metabolites produced by fungi and that has antibacterial
CC activity (PubMed:31304040, PubMed:31045362). The first step is
CC performed by the polyketide synthase VdtA which condenses one acetyl-
CC CoA and 6 malonyl-CoA units to form the heptaketide monomer backbone of
CC viriditoxin (PubMed:31304040). The product of VdtA is then O-methylated
CC on C7 by the O-methyltransferase VdtC (PubMed:31304040,
CC PubMed:31045362). The O-methyl group is important for the
CC stereoselective coupling of the monomers at the final step of
CC viriditoxin biosynthesis (PubMed:31304040, PubMed:31045362). The short-
CC chain dehydrogenase/reductase VdtF then acts as a stereospecific
CC reductase converting the pyrone to dihydropyrone via the reduction of
CC the C3-C4 double bond (PubMed:31304040, PubMed:31045362). The FAD-
CC binding monooxygenase VdtE then converts the ketone group into a
CC methyl-ester group to yield semi-viriditoxin (PubMed:31304040,
CC PubMed:31045362). Finally, the laccase VdtB is involved in dimerization
CC of 2 semi-viriditoxin molecules to yield the final viriditoxin
CC (PubMed:31304040, PubMed:31045362). VdtB is responsible for the
CC regioselective 6,6'-coupling of semi-viriditoxin, which yields (M)-
CC viriditoxin and (P)-viriditoxin at a ratio of 1:2 (PubMed:31304040,
CC PubMed:31045362). The non-catalytic carboxylesterase-like protein VdtD
CC affects the stereochemistical outcome of the coupling (PubMed:31304040,
CC PubMed:31045362). The highly reducing polyketide synthase VdtX is not
CC involved in viriditoxin synthesis, but might possibly play a role in
CC the production of additional metabolites not identified yet
CC (PubMed:31304040, PubMed:31045362). {ECO:0000269|PubMed:31045362,
CC ECO:0000269|PubMed:31304040}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-dihydroxy-7-methoxy-3-(2-oxopropyl)-1H-
CC benzo[g]isochromen-1-one + H(+) + NADPH + O2 = H2O + methyl 2-[(3S)-
CC 9,10-dihydroxy-7-methoxy-1-oxo-1H,3H,4H-naphtho[2,3-c]pyran-3-
CC yl]acetate + NADP(+); Xref=Rhea:RHEA:62868, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:146010, ChEBI:CHEBI:146012;
CC Evidence={ECO:0000269|PubMed:31045362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62869;
CC Evidence={ECO:0000269|PubMed:31045362};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-9,10-dihydroxy-7-methoxy-3-(2-oxopropyl)-1H,3H,4H-
CC naphtho[2,3-c]pyran-1-one + H(+) + NADPH + O2 = H2O + NADP(+) +
CC semiviriditoxin; Xref=Rhea:RHEA:62872, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:146008, ChEBI:CHEBI:146011;
CC Evidence={ECO:0000269|PubMed:31045362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62873;
CC Evidence={ECO:0000269|PubMed:31045362};
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: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31045362, ECO:0000269|PubMed:31304040}.
CC -!- DISRUPTION PHENOTYPE: Impairs the conversion of the ketone group into a
CC methyl-ester group to yield semi-viriditoxin.
CC {ECO:0000269|PubMed:31304040}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; RCNU01000014; RWQ92170.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A443HK11; -.
DR SMR; A0A443HK11; -.
DR Proteomes; UP000283841; Unassembled WGS sequence.
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; -; 3.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR020946; Flavin_mOase-like.
DR Pfam; PF00743; FMO-like; 1.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..571
FT /note="FAD-binding monooxygenase VdtE"
FT /id="PRO_0000448345"
FT BINDING 44..47
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 54..56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 56..57
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 187..193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 210..211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 336
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 571 AA; 64947 MW; DC42EF0094E618BF CRC64;
MASMQEVDAL VVGAGFGGLW MTNRLKEAGL NVLCVEKAPQ AGGVWYWNCY PGARVDSRYP
VYQYSDESLC KDWNWSELFP GYEEIRKYLS YAVDKWQLNS HIRYNTTVTG ARFDESDHKW
TVEGINGSHG TIRIRCRWYI LALGFASKPY IPDFEGLNRF QGPCFHSSAW PQEGIDLKGR
RVAVVGTGAS AVQIIQTISK EVGHLTVYQR TPCTAMPMRQ QSLTPEYQDN FKASGEMAAT
MRRTKYERFG GQDVQFVSRR WHEDTPEQRR AVFEQAWQKG GFHLLLSTYF EVFDDVEVNH
AAWRFWAEKS RERIHNTKYK DILAPLEAVH AFGGKRTPFE QDYFEAFNRR NVDLIDMKAS
PILSFAEKGI ITQNEGLQEF DVIILATGFD TNTGALTSIH IQDTDGILLK DRWSYDGVMT
TFGMSTSKFP NMFFFYGPQA PTAFSNGPSC IELQGEFVEE LILDMIGKGV TRVDTTSEAE
KRWKESTLSL WNQFVFSSTK GFYTGENIPG KKAEPLNWFG GFPRYRKALT ECRDGGYKEY
SLRSLPKVPD PEHRGLIDKV AVVTSAQPVG A
