VDTF1_BYSSP
ID VDTF1_BYSSP Reviewed; 305 AA.
AC A0A443HJZ3;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Short-chain dehydrogenase/reductase VdtF {ECO:0000303|PubMed:31304040};
DE EC=1.-.-.- {ECO:0000269|PubMed:31045362};
DE AltName: Full=Viriditoxin biosynthesis cluster protein F {ECO:0000303|PubMed:31304040};
GN Name=VdtF {ECO:0000303|PubMed:31304040}; ORFNames=C8Q69DRAFT_480057;
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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC that 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=AH2 + methyl 2-[(3S)-9,10-dihydroxy-7-methoxy-1-oxo-1H,3H,4H-
CC naphtho[2,3-c]pyran-3-yl]acetate = A + semiviriditoxin;
CC Xref=Rhea:RHEA:62876, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:146008, ChEBI:CHEBI:146012;
CC Evidence={ECO:0000269|PubMed:31045362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62877;
CC Evidence={ECO:0000269|PubMed:31045362};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-dihydroxy-7-methoxy-3-(2-oxopropyl)-1H-
CC benzo[g]isochromen-1-one + AH2 = (3S)-9,10-dihydroxy-7-methoxy-3-(2-
CC oxopropyl)-1H,3H,4H-naphtho[2,3-c]pyran-1-one + A;
CC Xref=Rhea:RHEA:62880, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:146010, ChEBI:CHEBI:146011;
CC Evidence={ECO:0000269|PubMed:31045362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62881;
CC Evidence={ECO:0000269|PubMed:31045362};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31045362, ECO:0000269|PubMed:31304040}.
CC -!- DISRUPTION PHENOTYPE: Impairs the reduction of the C3-C4 doucle bond in
CC the heptaketide monomer. {ECO:0000269|PubMed:31304040}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; RCNU01000014; RWQ92171.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A443HJZ3; -.
DR SMR; A0A443HJZ3; -.
DR Proteomes; UP000283841; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..305
FT /note="Short-chain dehydrogenase/reductase VdtF"
FT /id="PRO_0000448346"
FT ACT_SITE 206
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 56..64
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 83..86
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 139..141
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 267..269
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 305 AA; 32539 MW; 5491DA783C90EC3A CRC64;
MDGKALTASS LFDITGRVAV ITGGGTGLGL MMAKALEANG AKVYILGRRL EPLQEAAKQS
THGNIHPVQC SVTSHADLQG VVDHIAAKDG YINLLVNNAG ISTPNLGPHA TRPTPKWDIS
KVRDYWFHKS FADYAAVFET NTTASLMVTF AFLELLDKGN KKSEEEAKAS QARNGAGKAR
IEYVRSQVVT LSSVGGFGRD NSAFIYGASK AAATHMMKNL ATYLAPWKIR VNVIAPGYFN
TDMMGNFYKA TGGRLPASLA PEERFGDAQE IGGTIVYLAS KAGAYCNGMV LLVDGGYVSN
KPSSY
